Aristada

Antidepressant Augmentation Agents
Partial Dopamine Receptor Agonist Antipsychotics

Oral Administration Oral Solid Formulations

Oral immediate release tablets (e.g., Abilify):
May be administered without regard to meals.
 
Orally disintegrating tablets (e.g., Abilify DiscMelt):
Do not open the blister until ready to administer.
Do not push the tablet through the foil because this could damage the tablet.
Place the tablet on the tongue and allow to dissolve. Tablet disintegration occurs rapidly in saliva.
Do not take with liquid unless it is necessary to do so. Do not divide the tablets in half.
May be administered without regard to meals.
 
Oral tablets with sensor (e.g., Abilify Mycite):
General instructions:
Prior to patient use, the healthcare provider should facilitate the use of the product and its components (patch, application, portal) and ensure the patient is capable and willing to use smartphones and apps.
Before using any component of the system, instruct patients to download the Mycite app and follow all of the instructions for use and ensure that the app is compatible with the specific smartphone of the patient.
The system includes a web-based portal for healthcare providers and caregivers.
Advise patients that if their smartphone is lost, impaired, or disabled, some information collected by the system may be lost. If the patient's device is lost or disabled, the Mycite patch should be changed immediately and connected to a new mobile device using their current account information. Information previously synced to the patient's account will be available.
Mycite tablets:
May administer without regard to meals.
Swallow tablets whole; do not divide, crush, or chew.
The tablets are embedded with an Ingestible Event Marker (IEM) intended to track drug ingestion in conjunction with a wearable sensor (Mycite patch) and smartphone app.
Although most ingestion will be detected within 30 minutes, it may take up to two hours for the smartphone app and web portal to detect ingestion of the tablet. If the tablet is not detected after ingestion, do not repeat the dose.
It is not recommended to use the tablets to track drug ingestion in "real-time" or during an emergency because detection may be delayed or not occur.
Mycite patch:
The patch detects the signal from the IEM sensor embedded in the tablet after ingestion and transmits data to a smartphone.
Apply only when instructed by the Mycite smartphone application (Mycite app) to the left side of the body just above the lower edge of the rib cage.
Ensure that the app is paired with the patch prior to use. The status of the patch is indicated by a status icon in the app to inform the user that the patch is properly adhered and fully functioning.
Do not place the patch where the skin is scraped, cracked, inflamed, or irritated, or in an area that overlaps the most recently removed patch.
Do not remove the patch when showering, swimming, or exercising.
Change the patch weekly or sooner if needed. The app will prompt you to change the patch and will direct you to apply and remove the patch correctly.
Remove the patch when having an MRI and replace it with a new one as soon as possible. If there is skin irritation, remove the patch.

Oral Liquid Formulations

Oral solution:
Administer using a calibrated oral measuring device.
May be administered without regard to meals.
Storage: Opened bottles of aripiprazole oral solution can be used for up to 6 months after opening, but not beyond the expiration date on the bottle.

Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intramuscular Administration

Immediate-release intramuscular injection solution (i.e. Abilify short-acting injection):
For intramuscular (IM) use only. Do not administer intravenously or subcutaneously.
Available as a ready-to-use injectable solution.
Inject slowly and deeply into muscle mass.
Wait at least 2 hours between doses.
Discard any unused portion.
 
Extended-release intramuscular injection (i.e., Abilify Maintena) Single-Use Vial Preparation, Reconstitution, and Administration:
-Preparation of adapter-syringe assembly:
For intramuscular (IM) use only. Do not administer intravenously or subcutaneously.
Remove cover from vial adapter package. Do not remove vial adapter from package. Using vial adapter package to handle the vial adapter, attach the prepackaged luer lock syringe to the vial adapter.
Use the luer lock syringe to remove the vial adapter from the package and discard the vial adapter package. Do not touch the spike tip of the adapter at any time.
-Reconstitution and Dose preparation of single-use Vial for suspension:
Use appropriate aseptic technique and reconstitute at room temperature.
The lyophilized powder should be suspended with the 5 mL vial of Sterile Water for Injection supplied in the kit.
For the 400-mg vial, reconstitute with 1.9 mL of Sterile Water for Injection. For a 300-mg vial, reconstitute with 1.5 mL of Sterile Water for Injection.
Using the syringe with pre-attached hypodermic safety needle, withdraw pre-determined Sterile Water volume into the syringe.
Discard residual water that remains in the 5 mL vial of Sterile Water for Injection after reconstitution.
After slowly injecting the Sterile Water for Injection into the vial of lyophilized powder, withdraw air equal to pressure in the vial. Remove needle from the vial.
Engage the needle safety device using a one-handed technique. Gently press the sheath against a flat surface until the needle is firmly engaged in the needle protection sheath. Visually confirm that the needle is fully engaged into the needle protection sheath, and discard.
Shake the reconstituted vial vigorously for 30 seconds. The reconstituted suspension should be uniform, homogenous, opaque, and milky white in color.
Determine the recommended volume for injection.
Using the 400 mg reconstituted vial: 400 mg = 2 mL, 300 mg = 1.5 mL, 200 mg = 1 mL, 160 mg = 0.8 mL.
Using the 300 mg reconstituted vial: 300 mg = 1.5 mL, 200 mg = 1 mL, 160 mg = 0.8 mL.
Wipe top of the reconstituted vial with a sterile alcohol swab. Place and hold the reconstituted vial on a hard surface.
Attach the adapter-syringe assembly to vial by holding the outside of the adapter and pushing adapter's spike firmly through the rubber stopper until the adapter snaps in place.
Slowly withdraw recommended volume into the luer lock syringe. A small amount of excess product will remain in the vial.
Detach the luer lock syringe containing the suspension from the vial. Attach syringe to the appropriate needle.
For deltoid administration, use the 23 gauge, 1-inch needle in non-obese patients and the 22 gauge, 1.5-inch needle in obese patients.
For gluteal administration, use the 22 gauge, 1.5-inch needle in non-obese patients and the 21 gauge, 2-inch needle in obese patients.
Ensure needle is firmly seated on safety device with a push and clockwise twist; pull the needle cap straight from the needle.
-Dose Administration and Disposal once prepared from Vial:
For once-monthly deep intramuscular gluteal or deltoid injection by a health care professional only. Do not administer by any other route.
For single-use only. Discard any unused portion.
Use immediately after reconstitution and preparation of the syringe.
Slowly inject the recommended volume as a single deep IM injection into the gluteal or deltoid muscle.
Do not massage the injection site.
After the injection, engage the needle safety device using a one-handed technique. Gently press the sheath against a flat surface until the needle is firmly engaged in the needle protection sheath. Appropriately dispose of the vials, adapter, needles, and syringe.
Do not re-use any components of the kit.
For subsequent injections, rotate sites of injection between the two gluteal or deltoid muscles.
If not injected immediately, keep vial at room temperature and shake vigorously for at least 60 seconds to re-suspend before preparing the syringe for injection. Do not store suspension in a syringe.
Refer to the Administration Instructions section of the official product labeling for detailed visual aids which accompany the written instructions.
 
Extended-release intramuscular injection (i.e., Abilify Maintena) Pre-Filled Dual Chamber Syringe Preparation, Reconstitution, Administration, and Disposal:
For once-monthly deep intramuscular gluteal or deltoid injection by a health care professional only. Do not administer by any other route.
For single-use only. Discard any unused portion.
Use immediately after reconstitution and preparation of the pre-filled syringe.
Use appropriate aseptic technique and reconstitute at room temperature.
Push plunger rod slightly to engage threads. Then, rotate plunger rod until the rod stops rotating to release diluent.
After plunger rod is at complete stop, middle stopper will be at the indicator line.
Vertically shake the syringe vigorously for 20 seconds until the drug is uniformly milky-white. The reconstituted suspension should be opaque and milky white in color.
To inject, twist and pull off Over-cap and Tip-cap. Select the appropriate needle.
For deltoid administration, use the 23 gauge, 1-inch needle in non-obese patients and the 22 gauge, 1.5-inch needle in obese patients.
For gluteal administration, use the 22 gauge, 1.5-inch needle in non-obese patients and the 21 gauge, 2-inch needle in obese patients.
While holding needle cap, ensure the needle is firmly seated on the safety device with a push; twist clockwise until snugly fitted. Pull needle-cap straight up.
Hold syringe upright and advance plunger rod slowly to expel the air until the suspension fills the needle base. If it's not possible to advance the plunger rod to expel the air, check that the plunger rod is rotated to a complete stop.
Slowly inject as a single deep IM injection into the gluteal or deltoid muscle.
Do not massage the injection site.
After the injection, engage the needle safety device. Immediately discard the used syringe and unused needle in an approved sharps container. The unused needle should not be saved for future use.
For subsequent injections, rotate sites of injection between the two gluteal or deltoid muscles.
Refer to the Administration Instructions section of the official product labeling for detailed visual aids which accompany the written instructions.
 
Extended-release aripiprazole lauroxil intramuscular injection (i.e., Aristada)
-General Administration Guidelines:
For administration as a long-acting intramuscular injection by a health care professional. Do not administer by any other route.
Prior to administering Aristada, establish tolerability with oral aripiprazole in patients who have never taken aripiprazole. Due to the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.
The 441 mg dose may be administered in the deltoid or gluteal muscle, whereas all other doses (662 mg, 882 mg, and 1,064 mg) should be administered in the gluteal muscle.
When initiating Aristada in conjunction with a single dose of Aristada Initio 675 mg, avoid injecting both Aristada Initio and Aristada concurrently into the same deltoid or gluteal muscle.
The dose and dosing interval may be adjusted, taking into account the pharmacokinetics and prolonged-release characteristics of Aristada.
If early dosing is needed, the injection should not be given any earlier than 14 days after the previous injection. If the patient misses their scheduled dose, refer to the dosing and administration recommendations for patients which are determined by the length of time since the last injection.
-Extended-release aripiprazole lauroxil injection (i.e., Aristada) Pre-filled Syringe Preparation, Administration, and Disposal:
The kit contains a pre-filled syringe with Aristada sterile aqueous suspension and 2 or 3 safety needles depending upon the dose.
Tap the syringe at least 10 times to dislodge any material which may have settled and shake vigorously for at least 30 seconds to ensure uniform suspension.
If the syringe is not used within 15 minutes, shake again for 30 seconds.
Select the injection needle based on injection site and dosage, as follows. For patients with a larger amount of subcutaneous tissue overlaying the injection site muscle, use the longer of the needles provided.
441 mg dose: Deltoid (21 gauge, 1-inch or 20 gauge, 1.5-inch), or Gluteal (20 gauge, 1.5-inch or 20 gauge, 2-inch).
662 mg dose: Gluteal (20 gauge, 1.5-inch or 20 gauge, 2-inch).
882 mg dose: Gluteal (20 gauge, 1.5-inch or 20 gauge, 2-inch).
1,064 mg dose: Gluteal (20 gauge, 1.5-inch or 20 gauge, 2-inch).
Attach the injection needle to the syringe securely with a clockwise twisting motion. Do not over-tighten, since this may lead to needle hub cracking.
Prime the syringe to remove air.
Bring the syringe into an upright position and tap the syringe to bring air to the top. Remove air by depressing the plunger rod. A few drops of suspension will be released.
Administer the entire contents of the syringe IM. Do not inject by any other route. Inject in a rapid and continuous manner (less than 10 seconds).
Cover the needle by pressing the safety device. Immediately discard the used syringe and unused needle in an approved sharps container. The unused needles should not be saved for future use.
Refer to the Administration Instructions section of the official product labeling for detailed visual aids which accompany the written instructions.
 
Single-dose extended-release aripiprazole lauroxil intramuscular injection (i.e., Aristada Initio) Pre-filled Syringe Preparation, Administration, and Disposal:
Aristada Initio is not interchangeable with Aristada due to differing pharmacokinetics.
For use as a single intramuscular dose in the deltoid or gluteal muscle in patients initiating Aristada or after a missed dose of Aristada. Do not inject by any other route.
The kit contains a syringe with a sterile suspension of 675 mg/2.4 mL of Aristada Initio and 3 safety needles (a 2-inch 20 gauge needle with yellow needle hub, a 1.5-inch 20 gauge needle with yellow needle hub, and a 1-inch 21 gauge needle with a green needle hub).
This product should only be administered by a health care professional.
Avoid injecting Aristada Initio and Aristada concurrently into the same deltoid or gluteal muscle.
Tap the syringe at least 10 times to dislodge any settled material and vigorously shake the syringe for at least 30 seconds to ensure a uniform suspension.
If the syringe is not used within 15 minutes, shake again for 30 seconds.
Select needle size based on injection site. For patients with a larger amount of subcutaneous tissue overlaying the injection site muscle, use the longer of the needles provided.
Deltoid: 21 gauge, 1-inch or 20 gauge, 1.5-inch.
Gluteal: 20 gauge 1.5-inch or 20 gauge, 2-inch.
Attach the injection needle to the syringe securely with a clockwise twisting motion. Do not overtighten, since this could lead to needle hub cracking.
Prime the syringe to remove air by bringing syringe into upright position and tapping, then depress the plunger rod to remove air until a few drops are released. Small air bubbles in the syringe are normal.
Inject IM in a rapid and continuous manner. Product requires a rapid injection; do not hesitate.
Cover the needle by pressing the safety device. Immediately discard the used syringe and unused needle in an approved sharps container. The unused needle should not be saved for future use.
Refer to the Administration Instructions section of the official product labeling for detailed visual aids which accompany the written instructions.
 
Extended-release intramuscular injection (i.e., Abilify Asimtufii) Pre-Filled Syringe Preparation, Administration, and Disposal:
To be prepared and administered by a health care professional only.
For use as a single intramuscular dose every 2-months by gluteal IM injection only. Do not administer by any other route.
Prior to administration, ensure suspension is a uniform, homogenous suspension that is opaque and milky-white in color. Do not use if suspension is discolored or particulate matter is present
Remove Abilify Asimtufii pre-filled syringe from the package.
Tap the syringe on your hand at least 10 times, then shake the syringe vigorously for at least 10 seconds until the medication is uniform.
Select needle size based on patient body type.
For non-obese patients: 22-gauge, 1.5-inch safety needle with needle protection device (needle in black packaging)
For obese patients: 21-gauge, 2-inch safety needle with needle protection device (needle in green packaging)
Twist and pull off the pre-filled syringe tip-cap. While holding the base of the needle, ensure the needle is firmly seated on the safety device with a push. Gently twist clockwise until securely fitted.
When ready to administer the injection, hold the pre-filled syringe upright and remove the needle-cap straight up. Do not twist the needle-cap, as this may loosen the needle from the syringe.
Slowly advance the plunger rod upward to expel the air and until the suspension fills the needle base.
Slowly inject the entire contents of the pre-filled syringe IM into the gluteal muscle. Do not administer by any other route. Do not massage the injection site.
After the injection, press the safety shield on a hard surface to cover and lock the shield over the needle.
Immediately discard the used syringe and unused needle in an approved sharps container. The unused needle should not be saved for future use.

Severe

bradycardia / Rapid / 0.1-0.9
seizures / Delayed / 0-0.2
rhabdomyolysis / Delayed / 0-0.1
AV block / Early / 0-0.1
myocardial infarction / Delayed / 0-0.1
atrial fibrillation / Early / 0-0.1
cardiac arrest / Early / 0-0.1
atrial flutter / Early / 0-0.1
suicidal ideation / Delayed / Incidence not known
stroke / Early / Incidence not known
diabetic ketoacidosis / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
torsade de pointes / Rapid / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
laryngospasm / Rapid / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
tardive dyskinesia / Delayed / Incidence not known
neuroleptic malignant syndrome / Delayed / Incidence not known
water intoxication / Delayed / Incidence not known
SIADH / Delayed / Incidence not known
serotonin syndrome / Delayed / Incidence not known

Moderate

hyperglycemia / Delayed / 0-17.6
constipation / Delayed / 2.0-11.0
blurred vision / Early / 3.0-8.0
urinary incontinence / Early / 1.0-5.0
sinus tachycardia / Rapid / 2.0-2.0
myoclonia / Delayed / 0.1-1.0
peripheral edema / Delayed / 0-1.0
orthostatic hypotension / Delayed / 0.2-1.0
hyponatremia / Delayed / 0-1.0
memory impairment / Delayed / 0.1-0.9
delirium / Early / 0.1-0.9
hypotension / Rapid / 0.1-0.9
urinary retention / Early / 0.1-0.9
hypoglycemia / Early / 0.1-0.9
myasthenia / Delayed / 0.1-0.9
photophobia / Early / 0.1-0.9
dyspnea / Early / 0.1-0.9
elevated hepatic enzymes / Delayed / 0.1-0.9
palpitations / Early / 0.1-0.9
chest pain (unspecified) / Early / 0.1-0.9
hypertension / Early / 0.1-0.9
hypokalemia / Delayed / 0.1-0.9
impotence (erectile dysfunction) / Delayed / 0.1-0.9
complex sleep-related behaviors / Early / 0-0.1
thrombocytopenia / Delayed / 0-0.1
jaundice / Delayed / 0-0.1
hyperbilirubinemia / Delayed / 0-0.1
hepatitis / Delayed / 0-0.1
QT prolongation / Rapid / 0-0.1
angina / Early / 0-0.1
hyperprolactinemia / Delayed / 0-0.1
priapism / Early / 0-0.1
confusion / Early / Incidence not known
impaired cognition / Early / Incidence not known
depression / Delayed / Incidence not known
impulse control symptoms / Delayed / Incidence not known
dysphagia / Delayed / Incidence not known
fecal incontinence / Early / Incidence not known
diabetes mellitus / Delayed / Incidence not known
hypercholesterolemia / Delayed / Incidence not known
hypertriglyceridemia / Delayed / Incidence not known
hyperlipidemia / Delayed / Incidence not known
neutropenia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
hyperthermia / Delayed / Incidence not known
heat intolerance / Early / Incidence not known

Mild

headache / Early / 0-27.0
weight gain / Delayed / 2.2-26.3
drowsiness / Early / 3.0-23.0
agitation / Early / 19.0-19.0
insomnia / Early / 0-18.0
fatigue / Early / 2.0-17.0
anxiety / Delayed / 17.0-17.0
nausea / Early / 8.0-15.0
vomiting / Early / 3.0-14.0
skin irritation / Early / 12.4-12.4
dizziness / Early / 3.0-10.0
dyspepsia / Early / 9.0-9.0
fever / Early / 4.0-9.0
pharyngitis / Delayed / 3.0-9.0
appetite stimulation / Delayed / 3.0-7.0
restlessness / Early / 1.0-6.0
hypersalivation / Early / 4.0-6.0
lethargy / Early / 3.0-5.0
xerostomia / Early / 4.0-5.0
diarrhea / Early / 3.0-4.0
weight loss / Delayed / 1.0-4.0
dental pain / Delayed / 4.0-4.0
musculoskeletal pain / Early / 1.0-4.0
arthralgia / Delayed / 1.0-4.0
myalgia / Early / 2.0-4.0
abdominal pain / Early / 3.0-3.0
cough / Delayed / 3.0-3.0
irritability / Delayed / 2.0-2.0
epistaxis / Delayed / 2.0-2.0
rash / Early / 0.1-2.0
pruritus / Rapid / 0.1-1.0
libido decrease / Delayed / 0.1-0.9
gastroesophageal reflux / Delayed / 0.1-0.9
nocturia / Early / 0.1-0.9
nasal congestion / Early / 0.1-0.9
alopecia / Delayed / 0.1-0.9
photosensitivity / Delayed / 0.1-0.9
hirsutism / Delayed / 0.1-0.9
hyperhidrosis / Delayed / 0.1-0.9
syncope / Early / 0.2-0.5
somnambulism / Early / 0-0.1
libido increase / Delayed / 0-0.1
diplopia / Early / 0-0.1
urticaria / Rapid / 0-0.1
amenorrhea / Delayed / 0-0.1
orgasm dysfunction / Delayed / 0-0.1
mastalgia / Delayed / 0-0.1
gynecomastia / Delayed / 0-0.1
menstrual irregularity / Delayed / 0-0.1
asthenia / Delayed / 1.0
anorexia / Delayed / 1.0
injection site reaction / Rapid / 1.0
psychomotor impairment / Early / Incidence not known
hiccups / Early / Incidence not known
polydipsia / Early / Incidence not known
hypothermia / Delayed / Incidence not known

Children, suicidal ideation

Safety and efficacy of oral aripiprazole has been demonstrated in pediatric patients 6 years of age or older for selected indications. Injectable formulations of aripiprazole are not approved for those less than 18 years of age for any indication. Because oral aripiprazole is approved for the adjunct treatment of major depression in adults, a boxed warning in the product label describes the risk of suicidality and suicidal ideation in children, adolescent, and young adult patients receiving antidepressants. In a pooled analysis of placebo-controlled trials of antidepressants (n = 4,500 pediatrics and 77,000 adults), there was an increased risk for suicidal thoughts and behaviors in adults and pediatric individuals 24 years of age and younger receiving an antidepressant versus placebo, with considerable variation in the risk of suicidality among drugs. The difference in absolute risk of suicidal thoughts and behaviors across different indications was highest in those with major depression. Weigh the need for an antidepressant in children, adolescents, or young adults  against the risk of suicidality; it is unknown if this risk extends to adjunctive treatment or long-term use. Monitor all patients for symptom worsening or suicidality, especially at treatment initiation or after dose changes. Caregivers and/or patients should immediately notify the prescriber of changes in behavior or suicidal ideation. A change to the treatment regimen or discontinuation of aripiprazole may be necessary in patients with emerging suicidality or worsening depression.

Dementia, geriatric, stroke

Antipsychotics are not approved for the treatment of dementia-related psychosis in geriatric patients; avoid use of aripiprazole if possible due to an increase in morbidity and mortality in elderly patients with dementia receiving antipsychotics. Deaths have typically resulted from heart failure, sudden death, or infections (primarily pneumonia). An increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatal events, has also been reported. A low starting dose is recommended for the older adult patient if aripiprazole is used. The Beers Criteria consider antipsychotics to be potentially inappropriate medications (PIMs) in elderly patients except for treating schizophrenia, bipolar disorder, and nausea/vomiting during chemotherapy. The Beers panel recommends avoiding antipsychotics in geriatric patients with delirium, dementia, or Parkinson's disease. Non-pharmacological strategies are first-line options for treating delirium- or dementia-related behavioral problems unless they have failed or are not possible and the patient is a substantial threat to self or others. If antipsychotic use is necessary in geriatrics with a history of falls or fractures, consider reducing the use of other CNS depressants and implement other fall risk strategies. Due to the potential for antipsychotic-induced hyponatremia and SIADH, sodium levels should be closely monitored when aripiprazole is initiated and after dose changes. According to the federal Omnibus Budget Reconciliation Act (OBRA) regulations in residents of long-term care facilities, antipsychotic therapy should only be initiated in a patient with behavioral or psychological symptoms of dementia (BPSD) when the patient is a danger to self or others or has symptoms due to mania or psychosis. For acute conditions persisting beyond 7 days, appropriate non-pharmacologic interventions must be attempted, unless clinically contraindicated and documented. OBRA provides general dosing guidance for antipsychotic treatment of BPSD. Antipsychotics are subject to periodic review for effectiveness, medical necessity, gradual dose reduction (GDR), or rationale for continued use. Refer to the OBRA guidelines for complete information.

Abilify, Abilify Asimtufii, Abilify Discmelt, Abilify Maintena, Abilify Mycite, Aristada

Rx

Oral and parenteral atypical antipsychotic of the dopamine system stabilizers class
Used orally in adults for schizophrenia, bipolar I disorder, and as an adjunct for major depression; short-acting injection used for agitation; distinct extended-release IM injections are used for maintenance of selected indications; used orally in pediatric patients for schizophrenia, bipolar I disorder, Tourette's syndrome, or irritability due to autism
Boxed warning related to an increased risk of suicidality in children, adolescents, and young adults, as well as regarding increased mortality risk in elderly patients treated for dementia-related psychosis

For the treatment of schizophrenia. Oral dosage (immediate-release oral dosage forms, tablets, orally disentegrating tablets, oral solution) Adults

10 to 15 mg PO once daily is the starting and suggested target dosage. Titrate no more frequently than every 2 weeks. Max: 30 mg/day, but doses greater than 15 mg/day have not shown meaningful increased benefit. ORAL SOLUTION DOSING: Substitute for the tablet on a mg-per-mg basis, up to 25 mg. Patients receiving 30 mg tablets should receive 25 mg of the solution due to enhanced absorption of the solution at higher dosages. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In CYP2D6 poor metabolizers (CYP2D6 PMs), reduce to one-half of the usual dose, then titrate to clinical response. In CYP2D6 PMs who are receiving a strong CYP3A4 inhibitor, reduce to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase back to the original dose. SWITCHING FROM OTHER ANTIPSYCHOTICS: In 1 study, the following regimens were safe and effective: 1) initiation with simultaneous discontinuation of the current antipsychotic monotherapy; 2) immediate initiation with a 2-week taper of the current antipsychotic; or 3) a 2-week up-titration of aripiprazole while simultaneously tapering the current antipsychotic. Adverse events were comparable across treatment groups and time-limited.

Adolescents

2 mg PO once daily, initially. Increase to 5 mg PO once daily after 2 day, then after 2 more days increase to the target dose of 10 mg PO once daily. May titrate in 5 mg increments, usually every 2 weeks to assess effectiveness and tolerability. Max: 30 mg/day PO, but increased benefit beyond 10 mg/day has not been demonstrated. ORAL SOLUTION DOSING: Substitute for the tablet on a mg-per-mg basis, up to 25 mg. Patients receiving 30 mg tablets should receive 25 mg of the solution due to enhanced absorption of the solution at higher dosages. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In CYP2D6 poor metabolizers (CYP2D6 PMs), reduce to one-half of the usual dose, then adjust to clinical response. In CYP2D6 PMs who are receiving a strong CYP3A4 inhibitor, reduce to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase back to the original dose.

Oral dosage (aripiprazole tablet with sensor, Abilify Mycite) Adults

10 to 15 mg PO once daily is the starting and suggested target dosage. Titrate no more frequently than every 2 weeks. Max: 30 mg/day, but doses greater than 15 mg/day have not shown meaningful increased benefit. The use of Abilify Mycite to track drug ingestion in "real-time" or during an emergent event is not recommended because detection may be delayed or not occur. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In CYP2D6 poor metabolizers (CYP2D6 PMs), reduce to one-half of the usual dose, then titrate to clinical response. In CYP2D6 PMs receiving a strong CYP3A4 inhibitor, reduce to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase back to the original dose. SWITCHING FROM OTHER ANTIPSYCHOTICS: In 1 study, the following regimens were safe and effective: 1) initiation with simultaneous discontinuation of the current antipsychotic monotherapy; 2) immediate initiation with a 2-week taper of the current antipsychotic; or 3) a 2-week up-titration of aripiprazole while simultaneously tapering the current antipsychotic. Adverse events were comparable across treatment groups and time-limited.

Intramuscular dosage (once monthly extended-release injectable suspension; i.e. Abilify Maintena)

Establish tolerability with oral aripiprazole prior to initiating Abilify Maintena. Due to the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.

Adults

Abilify Maintena 400 mg IM once monthly, give maintenance doses no sooner than 26 days after the previous injection. At initiation, oral aripiprazole (10 to 20 mg per day) or other oral antipsychotic should be continued for 14 consecutive days to maintain therapeutic concentrations. Once stabilized, may reduce to 300 mg IM once monthly based upon tolerability. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In CYP2D6 poor metabolizers (CYP2D6 PMs), the recommended starting and maintenance dose is Abilify Maintena 300 mg IM once monthly. In CYP2D6 PMs receiving a CYP3A4 inhibitor for more than 14 days, reduce to 200 mg IM once monthly. MISSED DOSES: 1) If the second or third dose is missed and more than 4 weeks but less than 5 weeks have elapsed since the last injection: administer the injection as soon as possible. 2) If the second or third dose is missed and more than 5 weeks have elapsed since the last injection: restart concomitant oral aripiprazole for 14 days with the next administered injection. 3) If the fourth or subsequent dose is missed and greater than 4 weeks but less than 6 weeks have elapsed since the last injection: administer the injection as soon as possible. 4) If the fourth or subsequent dose is missed and more than 6 weeks have elapsed since the last injection: restart concomitant oral aripiprazole for 14 days with the next administered injection.

Intramuscular dosage (every 2-month extended-release injectable suspension; i.e., Abilify Asimtufii)

NOTE: Establish tolerability with oral aripiprazole prior to initiating Abilify Asimtufii. Due to the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability. 

Adults

Abilify Asimtufii 960 mg IM once every 2 months (56 days after previous injection). If needed, maintenance doses may be given up to 2 weeks before or 2 weeks after the 2-month scheduled time point. If there are adverse reactions to the 960 mg dosage, may decrease to 720 mg IM once every 2 months. INITIATION: When initiating in patients receiving oral aripiprazole or other oral antipsychotic, administer the first dose of Abilify Asimtufii and continue oral aripiprazole (10 to 20 mg per day) or the other oral antipsychotic for 14 consecutive days to maintain therapeutic concentrations. CONVERSION FROM ABILIFY MAINTENA EXTENDED RELEASE INJECTION: For patients receiving Abilify Maintena, administer Abilify Asimtufii in place of the next scheduled injection of Abilify Maintena. The first Abilify Asimtufii injection may be administered in place of the second or later injection of Abilify Maintena. ADJUSTMENTS: Coadministration of certain medications may need to be avoided or dosage adjustments may be necessary; review drug interactions. Patients who are taking 960 mg of Abilify Asimtufii and require a strong CYP2D6 or strong CYP3A4 inhibitor for more than 14 days should receive a reduced dose of 720 mg IM once every 2 months. In patients classified as CYP2D6 poor metabolizers (CYP2D6 PMs), the recommended dose is Abilify Asimtufii 720 mg IM once every 2 months. CYP2D6 PMs who are receiving a CYP3A4 inhibitor for more than 14 days should not use Abilify Asimtufii. MISSED DOSES: If more than 8 weeks and less than 14 weeks have elapsed since the last injection, administer the next dose of Abilify Asimtufii as soon as possible and resume the once every 2 month schedule. If more than 14 weeks have elapsed since the last injection, restart concomitant oral aripiprazole for 14 days with the next administered injection of Abilify Asimtufii.

Intramuscular dosage (extended-release aripiprazole lauroxil injectable suspension; i.e., Aristada)

NOTE: In aripiprazole-naive patients, establish tolerability with oral aripiprazole prior to initiating treatment with Aristada. Due to the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.

Adults 18 to 65 years of age

May initiate Aristada 441 mg, 662 mg, or 882 mg IM monthly, 882 mg IM every 6 weeks, or 1,064 mg IM every 2 months, according to individual needs of the patient. May adjust dosage and interval as needed, taking into account the pharmacokinetics and prolonged-release characteristics of Aristada. If early dosing is needed to accommodate the patient's schedule, do not give earlier than 14 days after the previous injection. THERE ARE TWO OPTIONS FOR INITIATING TREATMENT WITH ARISTADA. INITIATION OPTION ONE: Administer Aristada Initio 675 mg IM single dose and aripiprazole 30 mg PO single-dose in conjunction with the first Aristada injection. May give Aristada and Aristada Initio on the same day or up to 10 days thereafter; avoid injecting concurrently into the same muscle. INITIATION OPTION TWO: Continue oral aripiprazole for 21 consecutive days in conjunction with the first Aristada injection. SUGGESTED ARISTADA DOSAGE SELECTION FOR PATIENTS STABILIZED ON ORAL ARIPIPRAZOLE: 10 mg/day PO (Aristada 441 mg/month IM); 15 mg/day PO (Aristada 662 mg/month IM, 882 mg IM every 6 weeks, or 1,064 mg IM every 2 months); and 20 mg/day or higher PO (Aristada 882 mg/month IM). CONVERSION FROM ABILIFY MAINTENA EXTENDED-RELEASE IM INJECTION: Abilify Maintena doses of 300 mg, 450 mg, 600 mg, and 724 mg correspond to 441 mg, 662 mg, 882 mg, and 1,064 mg respectively, of Aristada. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In CYP2D6 poor metabolizers who are receiving a strong CYP3A4 inhibitor for more than 2 weeks, reduce the Aristada dose to 441 mg/month from 662 mg/month, 882 mg every month to 6 weeks, or 1,064 mg every 2 months. No dosage adjustment is needed for the 441 mg/month dose of Aristada, if tolerated. MISSED DOSES: 1) For patients who miss a dose while receiving 441 mg/month IM: If it has been 6 weeks or less since the missed dose, no oral supplementation is required. If it has been more than 6 weeks but not more than 7 weeks since the missed dose, supplement with 7 days of oral aripiprazole at the same dose of oral aripiprazole as when the patient began Aristada. If it has been more than 7 weeks since the missed dose, supplement with 21 days of oral aripiprazole at the same dose as when the patient began Aristada. 2) For patients who miss a dose while receiving 662 mg/month, 882 mg/month, or 882 mg every 6 weeks IM: If it has been 8 weeks or less since the missed dose, no oral supplementation is required. If it has been more than 8 weeks but not more than 12 weeks since the missed dose, supplement with 7 days of oral aripiprazole at the same dose as when the patient began Aristada. If it has been more than 12 weeks since the missed dose, supplement with 21 days of oral aripiprazole at the same dose of oral aripiprazole as when the patient began Aristada. 3) For patients who miss a dose while receiving 1,064 mg IM every 2 months: If it has been 10 weeks or less since the missed dose, no oral supplementation is required. If it has been more than 10 weeks but not more than 12 weeks since the missed dose, supplement with 7 days of oral aripiprazole at the same dose of oral aripiprazole as when the patient began Aristada. If it has been more than 12 weeks since the missed dose, supplement with 21 days of oral aripiprazole at the same dose as when the patient began Aristada.

Intramuscular dosage (extended-release aripiprazole lauroxil injection for single dose use; e.g., Aristada Initio ONLY)

NOTE: Aristada Initio is used as a single dose as part of an initiation regimen for Aristada, and is not interchangeable with Aristada due to differing pharmacokinetics.

Adults 18 to 65 years of age

Aristada Initio 675 mg IM as a single dose given with aripiprazole 30 mg PO single dose - these are given in conjunction with the first Aristada IM injection (at a different site) or up to 10 days thereafter. (Aristada Initio may also be used as a single dose to re-initiate Aristada following a missed dose of Aristada). Avoid use in CYP2D6 poor metabolizers. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For the treatment of bipolar disorder (bipolar I disorder), including acute treatment of mania and mixed episodes. For the acute treatment of mania and mixed episodes associated with bipolar I disorder. Oral dosage (immediate-release and disentegrating tablets) Adults

10 to 15 mg PO once daily, initially. May increase the dose based on clinical response and tolerability. Target dose: 15 mg/day. Max dose: 30 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Children and Adolescents 10 to 17 years

2 mg PO once daily for 2 days, then 5 mg PO once daily for 2 days, then 10 mg PO once daily. May further increase the dose by 5 mg/day based on clinical response and tolerability. Target dose: 10 mg/day. Max: 30 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Oral dosage (solution) Adults

10 to 15 mg PO once daily, initially. May increase the dose based on clinical response and tolerability. Target dose: 15 mg/day. Max dose: 25 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Children and Adolescents 10 to 17 years

2 mg PO once daily for 2 days, then 5 mg PO once daily for 2 days, then 10 mg PO once daily. May further increase the dose by 5 mg/day based on clinical response and tolerability. Target dose: 10 mg/day. Max: 25 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Oral dosage (tablet with sensor; e.g., Abilify Mycite) Adults

10 to 15 mg PO once daily, initially. May increase the dose based on clinical response and tolerability. Target dose: 15 mg/day. Max dose: 30 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For the maintenance treatment of bipolar I disorder. Oral dosage (tablet with sensor; e.g., Abilify Mycite) Adults

10 to 15 mg PO once daily, initially. May increase the dose based on clinical response and tolerability. Target dose: 15 mg/day. Max dose: 30 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Intramuscular dosage (monthly extended-release injectable suspension; i.e., Abilify Maintena) Adults

400 mg IM once monthly (no sooner than 26 days after the previous injection). Administer oral aripiprazole or other oral antipsychotic concurrently for 14 consecutive days to maintain therapeutic antipsychotic concentrations during initiation of therapy. May reduce dose to 300 mg IM once monthly for adverse reactions. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Intramuscular dosage (every 2-month extended-release injectable suspension; i.e., Abilify Asimtufii) Adults

960 mg IM every 2 months (56 days after the previous injection; may administer up to 2 weeks before or after the 2-month scheduled time point). May reduce dose to 720 mg IM every 2 months for adverse reactions. Coadministration of certain medications may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For the treatment of agitation associated with schizophrenia or bipolar mania. Intramuscular dosage (injection solution) Adults

9.75 mg IM as a single dose. A lower dosage of 5.25 mg IM may be used if clinically warranted such as patients classified as CYP2D6 poor metabolizers (CYP2D6 PMs). Subsequent administration may be considered if necessary; however, the efficacy of repeated dosages and the safety of administration more frequently than every 2 hours have not been established in controlled clinical trials. Maximum cumulative dose: 30 mg/day IM. Total daily doses greater than 30 mg have not been adequately studied. Single doses of 15 mg were not found superior to 9.75 mg in clinical trials. Patients requiring long-term treatment with aripiprazole should be changed to oral administration of the drug as soon as possible.

For the adjunctive treatment of major depression. Oral dosage Adults

Initially, 2 mg to 5 mg PO once daily as an adjunct to previously established antidepressant treatment. Adjust dose in increments of up to 5 mg at intervals of no less than 1 week each. The effective dose range is 2 mg/day to 15 mg/day PO. Periodically reassess to determine the need for continued treatment. It should be noted that the use of Abilify Mycite (aripiprazole tablets with sensor) to track drug ingestion in "real-time" or during an emergent event is not recommended because detection may be delayed or not occur. NOTE: No dosage adjustments are needed in patients with major depressive disorder receiving adjunct aripiprazole within this dose range with concomitant CYP modulators or for patients who are CYP2D6 poor metabolizers.

For the short-term treatment of irritability associated with autistic disorder. Oral dosage Children and Adolescents 6 years and older

Initially, 2 mg PO once daily. Increase dose to 5 mg PO once daily after 1 week. Further titration should occur in increments of 5 mg/day at intervals of no less than 1 week. Recommended dose range: 5 mg to 10 mg PO once daily. Individualize regimen based upon response and tolerability. Max: 15 mg/day PO. Periodically reassess to determine the need for continued treatment. Short-term efficacy was established in 2 placebo-controlled trials (8 week duration). In a maintenance trial, patients were initially stabilized with aripiprazole (2 mg/day to 15 mg/day) for 12 weeks (stabilization defined as greater than 25% improvement on the ABC-I subscale, and a CGI-I rating of much improved or very much improved). In the second phase of the maintenance trial (stabilized patients randomized to receive aripiprazole or placebo for an additional 16 weeks, n = 85), long-term efficacy was not established. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In patients classified as CYP2D6 poor metabolizers ( CYP2D6 PMs), reduce the initial oral aripiprazole dose to one-half of the usual dose, then adjust the dose to achieve a favorable clinical response. In patients classified as CYP2D6 PMs who are receiving a strong CYP3A4 inhibitor, reduce the oral aripiprazole dose to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase to the original dose (i.e., one-half of the usual dose).

For the treatment of Tourette's syndrome or chronic tic disorders†.
NOTE: The FDA has designated aripiprazole as an orphan drug for this indication.
Oral dosage Children and Adolescents 6 years and older

WEIGHING AT LEAST 50 KG: Initially, 2 mg PO once daily. After 2 days, increase to 5 mg PO once daily. Then, after 5 more days, increase to the target dose of 10 mg PO once daily. Increase gradually by 5 mg/day increments at weekly intervals as needed to achieve optimal control. Max: 20 mg/day PO. WEIGHING LESS THAN 50 KG: Initially, 2 mg PO once daily. After 2 days, increase dose to 5 mg PO once daily. Increase gradually at weekly intervals as needed. Max: 10 mg/day PO. In all patients, periodically reassess the need for continued maintenance treatment. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary during treatment with aripiprazole; review drug interactions. In CYP2D6 poor metabolizers (CYP2D6 PMs), reduce the initial oral aripiprazole dose to one-half of the usual dose, then adjust to favorable clinical response. In CYP2D6 PMs who are receiving a strong CYP3A4 inhibitor, reduce the oral aripiprazole dose to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase to the original dose (i.e., one-half of the usual dose). The American Academy of Neurology states that aripiprazole is probably more likely than placebo to reduce tic severity in patients with Tourette's syndrome or chronic tic disorders; however, there is insufficient evidence to determine the efficacy of aripiprazole relative to other antipsychotics used to treat tics.

For the treatment of severe behavioral or psychological symptoms of dementia† (BPSD)†. Oral dosage Geriatric Adults

Initially, 2 mg or 5 mg PO once daily, with gradual titration of the daily dose according to response and tolerance, usually by no more than 5 mg/day every week. Maximum suggested dose: 10 mg/day PO. A 2011 off-label use of review by the Agency for Healthcare Research and Quality (AHRQ) stated aripiprazole is efficacious for behavioral symptoms of dementia and for agitation. Antipsychotics are not FDA-approved for this indication and the labeling of all antipsychotics contains a boxed warning noting an increased risk of death in geriatric patients being treated for behavioral problems associated with dementia. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of antipsychotics in long-term care facility (LTCF) residents with dementia-related behavioral symptoms. OBRA Max: 10 mg/day PO in residents meeting the OBRA criteria for treatment, except when documentation is provided showing that higher doses are necessary to maintain or improve the resident's functional status. In addition, the facility must attempt a gradual dose reduction (GDR) in 2 separate quarters, at least 1 month apart, within the first year of admission to the facility or after the facility has initiated an antipsychotic, unless clinically contraindicated. After the first year, a GDR must be attempted annually unless clinically contraindicated. The GDR may be considered clinically contraindicated if the target symptoms returned or worsened after the most recent GDR attempt within the facility and the physician has documented justification for why attempting additional dose reductions at that time would likely impair the resident's function or increase distressed behavior. ORAL SOLUTION DOSING: The oral solution can be substituted for the tablet on a mg-per-mg basis, up to 25 mg. Patients receiving 30 mg tablets should receive 25 mg of the solution due to enhanced absorption of the solution at higher dosages. ADJUSTMENTS: Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In patients classified as CYP2D6 poor metabolizers (CYP2D6 PMs), reduce the initial oral aripiprazole dose to one-half of the usual dose, then adjust the dose to achieve a favorable clinical response. In patients classified as CYP2D6 PMs who are also receiving a strong CYP3A4 inhibitor, reduce the oral aripiprazole dose to one-quarter of the usual dose. When the CYP3A4 inhibitor is withdrawn, increase to the original dose (i.e., one-half of the usual dose).

†Indicates off-label use

Hepatic Impairment

No dosage adjustment for oral or parenteral aripiprazole is required on the basis of a patient's hepatic function (mild to severe hepatic impairment, Child-Pugh score between 5 and 15).

Renal Impairment

No dosage adjustment for oral or parenteral aripiprazole is required on the basis of a patient's renal function (mild to severe renal impairment, glomerular filtration rate between 15 and 90 mL/minute).
 
Intermittent hemodialysis
Hemodialysis is unlikely to be effective in removing aripiprazole since the drug is highly bound to plasma proteins.

Abarelix: (Major) Abarelix carries an established risk for QT prolongation. Prescribers need to weigh the potential benefits and risks of abarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
Abiraterone: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of abiraterone. Patients receiving both a CYP3A inhibitor plus abiraterone may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; abiraterone is a moderate CYP2D6 inhibitor.
Acarbose: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Acebutolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of diphenhydramine. Patients receiving both a CYP3A inhibitor plus diphenhydramine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; diphenhydramine is a moderate CYP2D6 inhibitor.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Acetaminophen; Codeine: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of doxylamine and aripiprazole due to the risk for additive CNS depression.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Drugs that can cause CNS depression, including dichloralphenazone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness if used concomitantly with atypical antipsychotics.
Acetaminophen; Diphenhydramine: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of diphenhydramine. Patients receiving both a CYP3A inhibitor plus diphenhydramine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; diphenhydramine is a moderate CYP2D6 inhibitor.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Acetaminophen; Oxycodone: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Acrivastine; Pseudoephedrine: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Adagrasib: (Major) Concomitant use of aripiprazole and adagrasib increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a strong CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP2D6 and CYP3A substrate, adagrasib is a moderate CYP2D6 and strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Major) Concomitant use of aripiprazole and adagrasib increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a strong CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP2D6 and CYP3A substrate, adagrasib is a moderate CYP2D6 and strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation.
Aldesleukin, IL-2: (Moderate) Because aripiprazole is metabolized by CYP3A4, increased aripiprazole blood levels may occur when the drug is coadministered with inhibitors of CYP3A4 such as aldesleukin, IL-2. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions, particularly CNS effects. In addition, because aripiprazole is also metabolized by CYP2D6, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adults receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inhibitor.
Alfentanil: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Alfuzosin: (Moderate) Concomitant use of aripiprazole and alfuzosin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Alogliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Alogliptin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Alogliptin; Pioglitazone: (Moderate) Monitor blood glucose during concomitant aripiprazole and pioglitazone use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Alpha-glucosidase Inhibitors: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Alprazolam: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
Amifampridine: (Major) Carefully consider the need for concomitant treatment with atypical antipsychotics and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Atypical antipsychotics may increase the risk of seizures.
Amiloride: (Moderate) Monitor blood pressure and adjust amiloride dose accordingly as aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and adjust amiloride dose accordingly as aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Amiodarone: (Major) Concomitant use of aripiprazole and amiodarone increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is necessary; management recommendations vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. Aripiprazole is CYP2D6 and CYP3A substrate, amiodarone is a weak CYP2D6 and moderate CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Major) Concomitant use of aripiprazole and amiodarone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with aripiprazole. Amisulpride causes dose- and concentration- dependent QT prolongation. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
Amitriptyline: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of aripiprazole and tricyclic antidepressants due to the risk for additive CNS depression.
Amlodipine: (Moderate) Monitor for aripiprazole-related adverse reactions and hypotension during concomitant use of amlodipine. Patients receiving both a CYP2D6 inhibitor plus amlodipine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Additionally, aripiprazole may enhance the hypotensive effects of antihypertensive agents such as amlodipine. Aripiprazole is a CYP3A and CYP2D6 substrate; amlodipine is a weak CYP3A inhibitor.
Amlodipine; Atorvastatin: (Moderate) Monitor for aripiprazole-related adverse reactions and hypotension during concomitant use of amlodipine. Patients receiving both a CYP2D6 inhibitor plus amlodipine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Additionally, aripiprazole may enhance the hypotensive effects of antihypertensive agents such as amlodipine. Aripiprazole is a CYP3A and CYP2D6 substrate; amlodipine is a weak CYP3A inhibitor.
Amlodipine; Benazepril: (Moderate) Monitor for aripiprazole-related adverse reactions and hypotension during concomitant use of amlodipine. Patients receiving both a CYP2D6 inhibitor plus amlodipine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Additionally, aripiprazole may enhance the hypotensive effects of antihypertensive agents such as amlodipine. Aripiprazole is a CYP3A and CYP2D6 substrate; amlodipine is a weak CYP3A inhibitor.
Amlodipine; Celecoxib: (Moderate) Monitor for aripiprazole-related adverse reactions and hypotension during concomitant use of amlodipine. Patients receiving both a CYP2D6 inhibitor plus amlodipine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Additionally, aripiprazole may enhance the hypotensive effects of antihypertensive agents such as amlodipine. Aripiprazole is a CYP3A and CYP2D6 substrate; amlodipine is a weak CYP3A inhibitor. (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of celecoxib. Patients receiving both a CYP3A inhibitor plus celecoxib may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; celecoxib is a weak CYP2D6 inhibitor.
Amlodipine; Olmesartan: (Moderate) Monitor for aripiprazole-related adverse reactions and hypotension during concomitant use of amlodipine. Patients receiving both a CYP2D6 inhibitor plus amlodipine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Additionally, aripiprazole may enhance the hypotensive effects of antihypertensive agents such as amlodipine. Aripiprazole is a CYP3A and CYP2D6 substrate; amlodipine is a weak CYP3A inhibitor.
Amlodipine; Valsartan: (Moderate) Monitor for aripiprazole-related adverse reactions and hypotension during concomitant use of amlodipine. Patients receiving both a CYP2D6 inhibitor plus amlodipine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Additionally, aripiprazole may enhance the hypotensive effects of antihypertensive agents such as amlodipine. Aripiprazole is a CYP3A and CYP2D6 substrate; amlodipine is a weak CYP3A inhibitor.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for aripiprazole-related adverse reactions and hypotension during concomitant use of amlodipine. Patients receiving both a CYP2D6 inhibitor plus amlodipine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Additionally, aripiprazole may enhance the hypotensive effects of antihypertensive agents such as amlodipine. Aripiprazole is a CYP3A and CYP2D6 substrate; amlodipine is a weak CYP3A inhibitor.
Amobarbital: (Major) Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. Additive CNS effects are possible, including drowsiness or dizziness. Patients should report any unusual changes in moods or behaviors while taking this combination.
Amoxapine: (Moderate) Use caution during co-administration of amoxapine and aripiprazole. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and antipsychotics.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Concomitant use of aripiprazole and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, clarithromycin is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Major) Concomitant use of aripiprazole and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, clarithromycin is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation.
Anagrelide: (Moderate) Concomitant use of aripiprazole and anagrelide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Angiotensin II receptor antagonists: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Angiotensin-converting enzyme inhibitors: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Apalutamide: (Major) Recommendations for managing aripiprazole and apalutamide vary by aripiprazole dosage form. For aripiprazole oral dosage forms, double the usual dose over 1 to 2 weeks. For extended-release aripiprazole injections administered monthly (Abilify Maintena) and every 2 months (Abilify Asimtufii), avoid concomitant use. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; apalutamide is a strong CYP3A inducer. (Major) Recommendations for managing aripiprazole and apalutamide vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), increase the 441 mg dose to 662 mg; no adjustments are necessary for other dosages. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; apalutamide is a strong CYP3A inducer.
Apomorphine: (Moderate) Use apomorphine and aripiprazole with caution due to a risk for QT prolongation and sedation. Apomorphine and aripiprazole may decrease the effectiveness of each other due to opposing effects on dopamine. Additive CNS effects are also possible. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. In general, atypical antipsychotics are less likely to interfere with Parkinson's disease treatments than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, sedation, fast, irregular heartbeat, and diminished effectiveness of either agent during coadministration.
Aprepitant, Fosaprepitant: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of aprepitant/fosaprepitant. Patients receiving both a CYP2D6 inhibitor plus aprepitant/fosaprepitant may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; aprepitant/fosaprepitant is a moderate CYP3A inhibitor.
Armodafinil: (Moderate) In vitro data indicate that armodafinil is an inducer of CYP3A4/5 isoenzymes. Decreased blood levels of aripiprazole are expected when the drug is coadministered with inducers of CYP3A4, such as armodafinil. A dosage adjustment of aripiprazole may be necessary when these drugs are used concomitantly, and conversely, when armodafinil is discontinued in a patient taking aripiprazole. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
Arsenic Trioxide: (Major) QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported.
Artemether; Lumefantrine: (Major) Avoid concomitant use of aripiprazole and lumefantrine, if possible, especially in patients with risk factors for torsade de pointes (TdP). If use is necessary in patients who are receiving both a CYP3A inhibitor plus lumefantrine, an aripiprazole dosage reduction may be required. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Additionally, monitor for aripiprazole-related adverse effects and consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Concomitant use may increase aripiprazole exposure and risk for QT prolongation and TdP. Aripiprazole is a CYP2D6 and CYP3A substrate, lumefantrine is a moderate CYP2D6 inhibitor, and both medications have been associated with QT prolongation.
Asciminib: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of asciminib. Patients receiving both a CYP2D6 inhibitor plus asciminib may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; asciminib is a weak CYP3A inhibitor.
Asenapine: (Major) Avoid concomitant use of aripiprazole and asenapine. If use is necessary, patients who are receiving both a CYP3A inhibitor plus asenapine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase the risk for QT prolongation and torsade de pointes (TdP), and may increase aripiprazole exposure and the risk for other aripiprazole-related adverse effects. Aripiprazole is a CYP3A and CYP2D6 substrate; asenapine is a weak CYP2D6 inhibitor. Both medications have been associated with QT prolongation and TdP. Both antipsychotic medications may affect coordination, reaction time, or judgment.
Aspirin, ASA; Butalbital; Caffeine: (Major) Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. Additive CNS effects are possible, including drowsiness or dizziness. Patients should report any unusual changes in moods or behaviors while taking this combination.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Aspirin, ASA; Oxycodone: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Atazanavir: (Major) Recommendations for managing aripiprazole and atazanavir vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; atazanavir is a strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and atazanavir vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; atazanavir is a strong CYP3A inhibitor.
Atazanavir; Cobicistat: (Major) Recommendations for managing aripiprazole and atazanavir vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; atazanavir is a strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and atazanavir vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; atazanavir is a strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and cobicistat vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a strong CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; cobicistat is a weak CYP2D6 and strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and cobicistat vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a strong CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; cobicistat is a weak CYP2D6 and strong CYP3A inhibitor.
Atenolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Atenolol; Chlorthalidone: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Atomoxetine: (Moderate) Concomitant use of aripiprazole and atomoxetine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with aripiprazole can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Avacopan: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of avacopan. Patients receiving both a CYP2D6 inhibitor plus avacopan may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; avacopan is a weak CYP3A inhibitor.
Azithromycin: (Major) Concomitant use of azithromycin and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Barbiturates: (Major) Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. Additive CNS effects are possible, including drowsiness or dizziness. Patients should report any unusual changes in moods or behaviors while taking this combination.
Bedaquiline: (Major) QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Bedaquiline has been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy. Coadministration with other QT prolonging drugs may result in additive or synergistic prolongation of the QT interval.
Belladonna; Opium: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Belumosudil: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of belumosudil. Patients receiving both a CYP2D6 inhibitor plus belumosudil may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; belumosudil is a weak CYP3A inhibitor.
Benzhydrocodone; Acetaminophen: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Benzodiazepines: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
Berotralstat: (Major) Recommendations for managing aripiprazole and berotralstat vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; berotralstat is a moderate CYP2D6 and moderate CYP3A inhibitor.
Beta-adrenergic blockers: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Betaxolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Bexarotene: (Moderate) Because aripiprazole is partially metabolized by CYP3A4, concurrent use of CYP3A4 inducers such as bexarotene may result in decreased plasma concentrations of aripiprazole. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. An increase in aripiprazole dosage may be clinically warranted in some patients. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
Bicalutamide: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of bicalutamide. Patients receiving both a CYP2D6 inhibitor plus bicalutamide may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; bicalutamide is a weak CYP3A inhibitor.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and aripiprazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and aripiprazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Bisoprolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Brexpiprazole: (Contraindicated) Concurrent use of brexpiprazole and aripiprazole should be avoided. Aripiprazole and brexpiprazole are both atypical antipsychotics of the dopamine system stabilizer subclass and have similar mechanisms of action. In addition, the risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, or seizures may be increased during combined use.
Brimonidine; Timolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Bromocriptine: (Moderate) The effectiveness of bromocriptine may be reduced by most of the atypical antipsychotics, via their action as dopamine antagonists. Monitor the patient for reduced response to bromocriptine. The atypical antipsychotics elevate prolactin to various degrees. Atypical antipsychotics may also aggravate diabetes mellitus and cause metabolic changes including hyperglycemia; use caution if bromocriptine is taken for diabetes. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
Brompheniramine: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Brompheniramine; Phenylephrine: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Brompheniramine; Pseudoephedrine: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Buprenorphine: (Major) Due to the potential for QT prolongation and additive CNS depressant effects, cautious use and close monitoring are advisable if concurrent use of aripiprazole and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If concurrent use of aripiprazole and buprenorphine is necessary, consider a dose reduction of one or both drugs. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Buprenorphine; Naloxone: (Major) Due to the potential for QT prolongation and additive CNS depressant effects, cautious use and close monitoring are advisable if concurrent use of aripiprazole and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If concurrent use of aripiprazole and buprenorphine is necessary, consider a dose reduction of one or both drugs. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Bupropion: (Major) Recommendations for managing aripiprazole and bupropion vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer half of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg. Further dosage reductions may be required in patients who are also receiving a CYP3A inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; bupropion is a strong CYP2D6 inhibitor. (Major) Recommendations for managing aripiprazole and bupropion vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg or for patients known to be poor metabolizers of CYP2D6. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP3A inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; bupropion is a strong CYP2D6 inhibitor.
Bupropion; Naltrexone: (Major) Recommendations for managing aripiprazole and bupropion vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer half of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg. Further dosage reductions may be required in patients who are also receiving a CYP3A inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; bupropion is a strong CYP2D6 inhibitor. (Major) Recommendations for managing aripiprazole and bupropion vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg or for patients known to be poor metabolizers of CYP2D6. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP3A inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; bupropion is a strong CYP2D6 inhibitor.
Buspirone: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant atypical antipsychotic and buspirone use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Butabarbital: (Major) Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. Additive CNS effects are possible, including drowsiness or dizziness. Patients should report any unusual changes in moods or behaviors while taking this combination.
Butalbital; Acetaminophen: (Major) Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. Additive CNS effects are possible, including drowsiness or dizziness. Patients should report any unusual changes in moods or behaviors while taking this combination.
Butalbital; Acetaminophen; Caffeine: (Major) Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. Additive CNS effects are possible, including drowsiness or dizzine

ss. Patients should report any unusual changes in moods or behaviors while taking this combination.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. Additive CNS effects are possible, including drowsiness or dizziness. Patients should report any unusual changes in moods or behaviors while taking this combination. (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. Additive CNS effects are possible, including drowsiness or dizziness. Patients should report any unusual changes in moods or behaviors while taking this combination. (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Butorphanol: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as aripiprazole, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Cabergoline: (Moderate) Cabergoline should not be coadministered with aripiprazole due to mutually antagonistic effects on dopaminergic function. The dopamine antagonist action of aripiprazole may diminish the prolactin-lowering ability of cabergoline while the dopamine agonist effects of cabergoline may exacerbate a psychotic disorder, reducing the effectiveness of antipsychotics such as aripiprazole.
Cabotegravir; Rilpivirine: (Moderate) Concomitant use of aripiprazole and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Minor) Coadministration of aripiprazole with famotidine decreases aripiprazole's solubility and rate of absorption. The Cmax of aripiprazole and the metabolite dehydroaripiprazole are decreased by 37% and 21%, respectively, and the AUC of aripiprazole and the dehydroaripiprazole metabolite are decreased by 13% and 15%, respectively. This interaction does not appear to cause clinically relevant effects and therefore no dosage adjustments are required.
Canagliflozin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Canagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and aripiprazole. Concurrent use may result in additive CNS depression.
Carbamazepine: (Major) Recommendations for managing aripiprazole and carbamazepine vary by aripiprazole dosage form. For aripiprazole oral dosage forms, double the usual dose over 1 to 2 weeks. For extended-release aripiprazole injections administered monthly (Abilify Maintena) and every 2 months (Abilify Asimtufii), avoid concomitant use. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; carbamazepine is a strong CYP3A inducer. (Major) Recommendations for managing aripiprazole and carbamazepine vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), increase the 441 mg dose to 662 mg; no adjustments are necessary for other dosages. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; carbamazepine is a strong CYP3A inducer.
Carbidopa; Levodopa: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Carbidopa; Levodopa; Entacapone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or COMT inhibitor during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and COMT inhibitors may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with COMT inhibitors and other Parkinson's treatments than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease. (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Carbinoxamine: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Cariprazine: (Moderate) The risk of adverse effects may be increased during concurrent use of cariprazine with other antipsychotics, such as aripiprazole. Similar to other antipsychotics, cariprazine administration has been associated with drowsiness, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. The incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, but the risk appears to be increased.
Carteolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Carvedilol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Celecoxib: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of celecoxib. Patients receiving both a CYP3A inhibitor plus celecoxib may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; celecoxib is a weak CYP2D6 inhibitor.
Celecoxib; Tramadol: (Major) Reserve concomitant use of tramadol and aripiprazole for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation as well as seizures. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, seizures, and death. (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of celecoxib. Patients receiving both a CYP3A inhibitor plus celecoxib may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; celecoxib is a weak CYP2D6 inhibitor.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and aripiprazole. Concurrent use may result in additive CNS depression.
Central-acting adrenergic agents: (Minor) Due to aripiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents.
Ceritinib: (Major) Concomitant use of aripiprazole and ceritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, ceritinib is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Major) Concomitant use of aripiprazole and ceritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, ceritinib is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation.
Cetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Cetirizine; Pseudoephedrine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Cetrorelix: (Moderate) Antipsychotic-induced hyperprolactinemia results in down-regulation of the number of pituitary GnRH receptors and may interfere with the response to any of the gonadotropin-releasing hormone (GnRH) analogs including cetrorelix.
Charcoal: (Major) Aripiprazole absorption is reduced when activated charcoal is coadministered within an hour of a 15 mg dosage, resulting in a decrease in aripiprazole AUC and Cmax by roughly 50%. Concomitant administration of aripiprazole with activated charcoal is not recommended. However, administration of activated charcoal may be appropriate in certain aripiprazole overdose situations.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Chloramphenicol: (Major) Recommendations for managing aripiprazole and chloramphenicol vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; chloramphenicol is a strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and chloramphenicol vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; chloramphenicol is a strong CYP3A inhibitor.
Chlorcyclizine: (Moderate) Additive CNS effects like drowsiness may be seen when combining sedating H1-blockers with atypical antipsychotics.
Chlordiazepoxide: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
Chlordiazepoxide; Amitriptyline: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone. (Moderate) Monitor for unusual drowsiness and sedation during coadministration of aripiprazole and tricyclic antidepressants due to the risk for additive CNS depression.
Chlordiazepoxide; Clidinium: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
Chloroquine: (Major) Avoid coadministration of chloroquine with aripiprazole due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Chlorpromazine: (Major) Avoid concomitant use of aripiprazole and chlorpromazine. If use is necessary in patients who are receiving both a CYP3A inhibitor plus chlorpromazine, an aripiprazole dosage reduction may be required. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase the risk for CNS depression, extrapyramidal symptoms (EPS), QT prolongation and torsade de pointes (TdP), and may increase aripiprazole exposure and the risk for other aripiprazole-related adverse effects. Aripiprazole is a CYP2D6 and CYP3A substrate; chlorpromazine is a moderate CYP2D6 inhibitor. Both medications have been associated with CNS depression, EPS, QT prolongation, and TdP.
Cimetidine: (Major) Recommendations for managing aripiprazole and cimetidine vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; cimetidine is a weak CYP2D6 and weak CYP3A inhibitor.
Cinacalcet: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of cinacalcet. Patients receiving both a CYP3A inhibitor plus cinacalcet may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; cinacalcet is a moderate CYP2D6 inhibitor.
Ciprofloxacin: (Moderate) Patients receiving both a CYP2D6 inhibitor plus ciprofloxacin may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Additionally, concomitant use may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Aripiprazole is a CYP3A and CYP2D6 substrate; ciprofloxacin is a moderate CYP3A inhibitor. Both medications have been associated with QT prolongation.
Cisapride: (Contraindicated) Avoid concomitant use of cisapride and aripiprazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Citalopram: (Major) Avoid concomitant use of aripiprazole and citalopram, if possible, especially in patients with risk factors for torsade de pointes (TdP). If use is necessary, patients receiving both a CYP3A inhibitor plus citalopram may require an aripiprazole dosage adjustment; dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Additionally, monitor for aripiprazole-related adverse effects and consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Concomitant use may increase aripiprazole exposure and increase the risk for QT prolongation and TdP. Aripiprazole is a CYP2D6 and CYP3A substrate; citalopram is a weak CYP2D6 inhibitor. Both medications have been associated with QT prolongation.
Clarithromycin: (Major) Concomitant use of aripiprazole and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, clarithromycin is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Major) Concomitant use of aripiprazole and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, clarithromycin is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation.
Clemastine: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Clobazam: (Moderate) Clobazam, a benzodiazepine, should be combined cautiously with atypical antipsychotics because of the potential for additive CNS depressant effects. Antipsychotics may also lower the seizure threshold, which might effect the efficacy of clobazam to treat seizures. Clobazam is a weak inducer of CYP3A4 and may reduce the efficacy of atypical antipsychotics that are significantly metabolized by CYP3A4; consult the atypical antipsychotic product labeling for clinical relevance.
Clofazimine: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of clofazimine. Patients receiving both a CYP2D6 inhibitor plus clofazimine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Additionally, concomitant use may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Aripiprazole is a CYP3A and CYP2D6 substrate; clofazimine is a weak CYP3A inhibitor. Both medications have been associated with QT prolongation.
Clomipramine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of aripiprazole and tricyclic antidepressants due to the risk for additive CNS depression.
Clonazepam: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
Clorazepate: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
Clozapine: (Major) QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Clozapine is an atypical antipsychotic with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with aripiprazole. In addition, caution is advisable when aripiprazole is given in combination with other CNS depressants such as other atypical antipsychotics. The risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, tardive dyskinesia, or seizures may be increased during combined use; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is deemed necessary. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent.
Cobicistat: (Major) Recommendations for managing aripiprazole and cobicistat vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a strong CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; cobicistat is a weak CYP2D6 and strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and cobicistat vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a strong CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; cobicistat is a weak CYP2D6 and strong CYP3A inhibitor.
Codeine: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Codeine; Guaifenesin: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of aripiprazole and promethazine may increase the risk of CNS depression and QT/QTc prolongation and torsade de pointes (TdP) in some patients. Monitor for unusual drowsiness and excess sedation and consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Codeine; Promethazine: (Moderate) Concomitant use of aripiprazole and promethazine may increase the risk of CNS depression and QT/QTc prolongation and torsade de pointes (TdP) in some patients. Monitor for unusual drowsiness and excess sedation and consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
COMT inhibitors: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or COMT inhibitor during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and COMT inhibitors may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with COMT inhibitors and other Parkinson's treatments than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Conivaptan: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of conivaptan. Patients receiving both a CYP2D6 inhibitor plus conivaptan may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; conivaptan is a moderate CYP3A inhibitor.
Crizotinib: (Major) Avoid concomitant use aripiprazole and crizotinib, if possible, especially in patients with risk factors for torsade de pointes (TdP). If concomitant use is necessary, patients receiving both a CYP2D6 inhibitor plus crizotinib may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. Additionally, consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Concomitant use increases the risk for QT/QTc prolongation and TdP and may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate, crizotinib is a moderate CYP3A inhibitor, and both medications have been associated with QT interval prolongation.
Cyclizine: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Cyclosporine: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of cyclosporine. Patients receiving both a CYP2D6 inhibitor plus cyclosporine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; cyclosporine is a moderate CYP3A inhibitor.
Cyproheptadine: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Dacomitinib: (Major) Recommendations for managing aripiprazole and dacomitinib vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer half of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg. Further dosage reductions may be required in patients who are also receiving a CYP3A inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; dacomitinib is a strong CYP2D6 inhibitor. (Major) Recommendations for managing aripiprazole and dacomitinib vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg or for patients known to be poor metabolizers of CYP2D6. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP3A inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; dacomitinib is a strong CYP2D6 inhibitor.
Dalfopristin; Quinupristin: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of quinupristin. Patients receiving both a CYP2D6 inhibitor plus quinupristin may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; quinupristin is a weak CYP3A inhibitor.
Danazol: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of danazol. Patients receiving both a CYP2D6 inhibitor plus danazol may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; danazol is a moderate CYP3A inhibitor.
Dapagliflozin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Dapagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Dapagliflozin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Darifenacin: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of darifenacin. Patients receiving both a CYP3A inhibitor plus darifenacin may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; darifenacin is a moderate CYP2D6 inhibitor.
Darunavir: (Major) Recommendations for managing aripiprazole and darunavir vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; darunavir is a strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and darunavir vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; darunavir is a strong CYP3A inhibitor.
Darunavir; Cobicistat: (Major) Recommendations for managing aripiprazole and cobicistat vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a strong CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; cobicistat is a weak CYP2D6 and strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and cobicistat vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a strong CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; cobicistat is a weak CYP2D6 and strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and darunavir vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; darunavir is a strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and darunavir vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; darunavir is a strong CYP3A inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Recommendations for managing aripiprazole and cobicistat vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a strong CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; cobicistat is a weak CYP2D6 and strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and cobicistat vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a strong CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; cobicistat is a weak CYP2D6 and strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and darunavir vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; darunavir is a strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and darunavir vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; darunavir is a strong CYP3A inhibitor.
Dasatinib: (Moderate) Concomitant use of aripiprazole and dasatinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Degarelix: (Moderate) Concomitant use of aripiprazole and androgen deprivation therapy (i.e., degarelix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Delavirdine: (Major) Recommendations for managing aripiprazole and delavirdine vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; delavirdine is a strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and delavirdine vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; delavirdine is a strong CYP3A inhibitor.
Desipramine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of aripiprazole and tricyclic antidepressants due to the risk for additive CNS depression.
Desvenlafaxine: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of desvenlafaxine at a dose of at least 400 mg/day. Patients receiving both a CYP3A inhibitor plus desvenlafaxine at a dose of at least 400 mg/day may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; desvenlafaxine at a dose of at least 400 mg/day is a weak CYP2D6 inhibitor.
Deutetrabenazine: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and aripiprazole. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and aripiprazole is a partial dopamine agonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Monitor for excessive sedation and somnolence during coadministration of aripiprazole and deutetrabenazine. Concurrent use may result in additive CNS depression.
Dexchlorpheniramine: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Dexmedetomidine: (Moderate) Concomitant use of dexmedetomidine and aripiprazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Dextromethorphan; Bupropion: (Major) Recommendations for managing aripiprazole and bupropion vary by aripiprazole dosage form . For aripiprazole oral dosage forms, administer half of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg. Further dosage reductions may be required in patients who are also receiving a CYP3A inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; bupropion is a strong CYP2D6 inhibitor. (Major) Recommendations for managing aripiprazole and bupropion vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg or for patients known to be poor metabolizers of CYP2D6. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP3A inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; bupropion is a strong CYP2D6 inhibitor.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of diphenhydramine. Patients receiving both a CYP3A inhibitor plus diphenhydramine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; diphenhydramine is a moderate CYP2D6 inhibitor.
Dextromethorphan; Quinidine: (Contraindicated) Avoid use of aripiprazole with quinidine unless the benefit outweighs the risk. Quinidine is generally contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6, such as aripiprazole, as the effects on the QT interval may be increased. Manufacturer recommendations for this combination have varied. Do not use the combination product of dextromethorphan; quinidine with aripiprazole. The manufacturers of aripiprazole products do not contraindicate use of quinidine, but recommend dosage adjustments of aripiprazole when used with potent CYP2D6 inhibitors, such as quinidine. For example, the oral aripiprazole dose should be reduced by 50%. Injectable forms of aripiprazole require dose adjustment when the potent CYP2D6 inhibitor will be used for more than 14 days. See the manufacturer prescribing information for detailed recommendations. Both aripiprazole and quinidine are associated with QT prolongation. Increased aripiprazole exposure is likely when a potent CYP2D6 inhibitor like quinidine is used concurrently. In one evaluation, concurrent use of quinidine and oral aripiprazole resulted in an increase in the AUC of aripiprazole of 112% and a decrease in the AUC of its active metabolite by 35%.
Diazepam: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
Diazoxide: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Diltiazem: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of diltiazem. Patients receiving both a CYP2D6 inhibitor plus diltiazem may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; diltiazem is a moderate CYP3A inhibitor.
Dimenhydrinate: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of dimenhydrinate and aripiprazole due to the risk for additive CNS depression.
Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Diphenhydramine: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of diphenhydramine. Patients receiving both a CYP3A inhibitor plus diphenhydramine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; diphenhydramine is a moderate CYP2D6 inhibitor.
Diphenhydramine; Ibuprofen: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of diphenhydramine. Patients receiving both a CYP3A inhibitor plus diphenhydramine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; diphenhydramine is a moderate CYP2D6 inhibitor.
Diphenhydramine; Naproxen: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of diphenhydramine. Patients receiving both a CYP3A inhibitor plus diphenhydramine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; diphenhydramine is a moderate CYP2D6 inhibitor.
Diphenhydramine; Phenylephrine: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of diphenhydramine. Patients receiving both a CYP3A inhibitor plus diphenhydramine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; diphenhydramine is a moderate CYP2D6 inhibitor.
Diphenoxylate; Atropine: (Moderate) Concurrent administration of diphenoxylate/difenoxin with aripiprazole can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Disopyramide: (Major) Concomitant use of disopyramide and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dofetilide: (Major) Concomitant use of dofetilide and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dolasetron: (Moderate) Concomitant use of aripiprazole and dolasetron may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Dolutegravir; Rilpivirine: (Moderate) Concomitant use of aripiprazole and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Donepezil: (Moderate) Concomitant use of aripiprazole and donepezil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Donepezil; Memantine: (Moderate) Concomitant use of aripiprazole and donepezil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Dorzolamide; Timolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Doxazosin: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Doxepin: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of aripiprazole and tricyclic antidepressants due to the risk for additive CNS depression.
Doxylamine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of doxylamine and aripiprazole due to the risk for additive CNS depression.
Doxylamine; Pyridoxine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of doxylamine and aripiprazole due to the risk for additive CNS depression.
Dronabinol: (Moderate) Drugs that can cause CNS depression such as dronabinol, if used concomitantly with atypical antipsychotics, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
Dronedarone: (Contraindicated) Avoid concomitant use of aripiprazole and dronedarone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. (Contraindicated) Avoid concomitant use of aripiprazole and dronedarone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use also increases aripiprazole exposure and risk for side effects. If concomitant use is necessary, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. Aripiprazole is CYP2D6 and CYP3A substrate, dronedarone is a moderate CYP2D6 and CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation.
Droperidol: (Major) According to the manufacturer of droperidol, any drug known to have the potential to prolong the QT interval should not be used together with droperidol. The product labeling contains a boxed warning regarding the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. If concurrent use is unavoidable, extreme caution is recommended.
Dulaglutide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Duloxetine: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of duloxetine. Patients receiving both a CYP3A inhibitor plus duloxetine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; duloxetine is a moderate CYP2D6 inhibitor.
Duvelisib: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of duvelisib. Patients receiving both a CYP2D6 inhibitor plus duvelisib may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; duvelisib is a moderate CYP3A inhibitor.
Efavirenz: (Moderate) Consider alternatives to efavirenz when coadministering with aripiprazole as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. In addition, decreased aripiprazole blood levels are expected when aripiprazole is coadministered with inducers of CYP3A4, such as efavirenz. Monitor the patient carefully for toxicity and efficacy if these agents are used in combination. Dosage adjustments of aripiprazole may be clinically warranted in some patients. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with aripiprazole as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. In addition, decreased aripiprazole blood levels are expected when aripiprazole is coadministered with inducers of CYP3A4, such as efavirenz. Monitor the patient carefully for toxicity and efficacy if these agents are used in combination. Dosage adjustments of aripiprazole may be clinically warranted in some patients. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with aripiprazole as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. In addition, decreased aripiprazole blood levels are expected when aripiprazole is coadministered with inducers of CYP3A4, such as efavirenz. Monitor the patient carefully for toxicity and efficacy if these agents are used in combination. Dosage adjustments of aripiprazole may be clinically warranted in some patients. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
Elagolix: (Moderate) Because aripiprazole is partially metabolized by CYP3A4, caution is advisable during coadministration of a CYP3A4 inducer, such as elagolix. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. A dose adjustment of aripiprazole may be needed. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) Because aripiprazole is partially metabolized by CYP3A4, caution is advisable during coadministration of a CYP3A4 inducer, such as elagolix. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. A dose adjustment of aripiprazole may be needed. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
Elbasvir; Grazoprevir: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of grazoprevir. Patients receiving both a CYP2D6 inhibitor plus grazoprevir may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; grazoprevir is a weak CYP3A inhibitor.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of ivacaftor. Patients receiving both a CYP2D6 inhibitor plus ivacaftor may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; ivacaftor is a weak CYP3A inhibitor.
Eliglustat: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of eliglustat. Patients receiving both a CYP3A inhibitor plus eliglustat may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Additionally, consider taking steps to minimize the risk of QT/QTc interval prolongation and torsade de pointes (TdP), such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Concomitant use may increase aripiprazole exposure and risk for side effects and may increase the risk of QT/QTc prolongation and TdP in some patients. Aripiprazole is a CYP2D6 and CYP3A substrate; eliglustat is a moderate CYP2D6 inhibitor; both medications have been associated with QT interval prolongation.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Recommendations for managing aripiprazole and cobicistat vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a strong CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; cobicistat is a weak CYP2D6 and strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and cobicistat vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a strong CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; cobicistat is a weak CYP2D6 and strong CYP3A inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Recommendations for managing aripiprazole and cobicistat vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a strong CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; cobicistat is a weak CYP2D6 and strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and cobicistat vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a strong CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; cobicistat is a weak CYP2D6 and strong CYP3A inhibitor.
Empagliflozin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Empagliflozin; Linagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Empagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Concomitant use of aripiprazole and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of aripiprazole and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Encorafenib: (Major) Avoid concomitant use of aripiprazole and encorafenib, if possible, especially in patients with risk factors for torsade de pointes (TdP). If use is necessary, patients receiving both a CYP2D6 inhibitor plus encorafenib may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Additionally, monitor for aripiprazole-related adverse effects and consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Concomitant use may increase aripiprazole exposure and risk for QT prolongation and TdP. Aripiprazole is a CYP3A and CYP2D6 substrate, encorafenib is a weak CYP3A inhibitor, and both medications have been associated with QT prolongation.
Entacapone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or COMT inhibitor during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and COMT inhibitors may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with COMT inhibitors and other Parkinson's treatments than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Entrectinib: (Major) Concomitant use of entrectinib and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Enzalutamide: (Major) Recommendations for managing aripiprazole and enzalutamide vary by aripiprazole dosage form. For aripiprazole oral dosage forms, double the usual dose over 1 to 2 weeks. For extended-release aripiprazole injections administered monthly (Abilify Maintena) and every 2 months (Abilify Asimtufii), avoid concomitant use. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; enzalutamide is a strong CYP3A inducer. (Major) Recommendations for managing aripiprazole and enzalutamide vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), increase the 441 mg dose to 662 mg; no adjustments are necessary for other dosages. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; enzalutamide is a strong CYP3A inducer.
Eplerenone: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Epoprostenol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Eribulin: (Major) Concomitant use of aripiprazole and eribulin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ertugliflozin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Ertugliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Ertugliflozin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Erythromycin: (Major) Avoid concomitant use aripiprazole and erythromycin, if possible, especially in patients with risk factors for torsade de pointes (TdP). If concomitant use is necessary, patients receiving both a CYP2D6 inhibitor plus erythromycin may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. Additionally, consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Concomitant use increases the risk for QT/QTc prolongation and TdP and may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate, erythromycin is a moderate CYP3A inhibitor, and both medications have been associated with QT interval prolongation.
Escitalopram: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of escitalopram. Patients receiving both a CYP3A inhibitor plus escitalopram may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Additionally, consider taking steps to minimize the risk of QT/QTc interval prolongation and torsade de pointes (TdP), such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Concomitant use may increase aripiprazole exposure and risk for side effects and may increase the risk of QT/QTc prolongation and TdP in some patients. Aripiprazole is a CYP2D6 and CYP3A substrate; escitalopram is a moderate CYP2D6 inhibitor; both medications have been associated with QT interval prolongation.
Esketamine: (Moderate) Closely monitor patients receiving esketamine and aripiprazole for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
Eslicarbazepine: (Moderate) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4. Coadministration of CYP3A4 substrates, such as aripiprazole, may result in decreased serum concentrations of the substrate. Monitor for decreased efficacy of aripiprazole if coadministered with eslicarbazepine. Dosage adjustments of aripirazole may be necessary. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
Esmolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Estazolam: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
Eszopiclone: (Moderate) A reduction in the dose of eszopiclone should be considered during co-administration of other CNS depressants, such as antipsychotics, to minimize additive sedative effects. In addition, the risk of next-day psychomotor impairment is increased during co-administration of eszopiclone and other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving. Antipsychotics with a higher incidence of sedation, such as olanzapine, clozapine, quetiapine, lurasidone, chlorpromazine, and thioridazine, are more likely to interact with eszopiclone. In one evaluation, concurrent use of eszopiclone and olanzapine reduced psychomotor function as measured by the Digit Symbol Substitution Test (DSST).
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Etravirine: (Moderate) Because aripiprazole is partially metabolized by CYP3A4, caution is advisable during use of a CYP3A4 inducer, such as etravirine. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
Everolimus: (Major) Recommendations for managing aripiprazole and everolimus vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; everolimus is a weak CYP2D6 and weak CYP3A inhibitor.
Exenatide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Famotidine: (Minor) Coadministration of aripiprazole with famotidine decreases aripiprazole's solubility and rate of absorption. The Cmax of aripiprazole and the metabolite dehydroaripiprazole are decreased by 37% and 21%, respectively, and the AUC of aripiprazole and the dehydroaripiprazole metabolite are decreased by 13% and 15%, respectively. This interaction does not appear to cause clinically relevant effects and therefore no dosage adjustments are required.
Fedratinib: (Major) Recommendations for managing aripiprazole and fedratinib vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; fedratinib is a moderate CYP2D6 and moderate CYP3A inhibitor.
Felodipine: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and aripiprazole. Concurrent use may result in additive CNS depression.
Fenoldopam: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Fentanyl: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Fingolimod: (Moderate) Concomitant use of aripiprazole and fingolimod may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Flecainide: (Major) Concomitant use of aripiprazole and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluconazole: (Contraindicated) Avoid use of aripiprazole with fluconazole unless the benefit outweighs the risk of QT prolongation or other side effects. Conflicting recommendations regarding concomitant use are available from the manufacturers of the drugs. According to the manufacturer of fluconazole, coadministration of drugs known to prolong the QT interval and which are CYP3A substrates, such as aripiprazole, is contraindicated in patients receiving fluconazole. The manufacturers of aripiprazole products do not contraindicate use of fluconazole, but do recommend dosage reductions in patients who are also receiving a CYP2D6 inhibitor. Specific dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Aripiprazole is a CYP3A and CYP2D6 substrate, fluconazole is a moderate CYP3A inhibitor, and both medications have been associated with QT prolongation.
Fluoxetine: (Major) Reduce the oral aripiprazole dosage by one-half of the usual dose in patients receiving strong CYP2D6 inhibitors such as fluoxetine. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP3A4 inhibitor, as aripiprazole is also metabolized by CYP3A4. Addtionally, aripiprazole and fluoxetine are both associated with prolongation of the QT interval; caution and close monitoring are recommended. Avoid concurrent use of Aristada Initio and fluoxetine because the dose of Aristada Initio cannot be modified. For other long-active aripiprazole injectables (e.g., Ability Maintena, Aristada), dose adjustments are recommended with strong CYP2D6 inhibitors and combined strong CYP2D6/CYP3A4 inhibitors; the recommendations are dependent on the aripiprazole IM depot dosage, the product given, and the duration of the concomitant inhibitors as specified in the product labels.
Fluphenazine: (Major) Fluphenazine,a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation, such as aripiprazole. Co-administration of fluphenazine with atypical agents (e.g., lurasidone and others) may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Flurazepam: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
Fluvoxamine: (Major) Concomitant use of aripiprazole and fluvoxamine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients and increases aripiprazole exposure and risk for side effects. An aripiprazole dosage reduction is necessary; management recommendations vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. Additionally, consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Aripiprazole is CYP2D6 and CYP3A substrate, fluvoxamine is a weak CYP2D6 and moderate CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Moderate) Concomitant use of aripiprazole and fluvoxamine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Fosamprenavir: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of fosamprenavir. Patients receiving both a CYP2D6 inhibitor plus fosamprenavir may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; fosamprenavir is a moderate CYP3A inhibitor.
Foscarnet: (Major) Concomitant use of aripiprazole and foscarnet increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fosphenytoin: (Major) Recommendations for managing aripiprazole and phenytoin/fosphenytoin vary by aripiprazole dosage form. For aripiprazole oral dosage forms, double the usual dose over 1 to 2 weeks. For extended-release aripiprazole injections administered monthly (Abilify Maintena) and every 2 months (Abilify Asimtufii), avoid concomitant use. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; phenytoin/fosphenytoin is a strong CYP3A inducer. (Major) Recommendations for managing aripiprazole and phenytoin/fosphenytoin vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), increase the 441 mg dose to 662 mg; no adjustments are necessary for other dosages. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; phenytoin/fosphenytoin are strong CYP3A inducers.
Fostamatinib: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of fostamatinib. Patients receiving both a CYP2D6 inhibitor plus fostamatinib may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; fostamatinib is a weak CYP3A inhibitor.
Fostemsavir: (Moderate) Concomitant use of aripiprazole and fostemsavir may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with fostemsavir is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 4 times the recommended daily dose.
Gabapentin: (Moderate) Monitor for respiratory depression and sedation during concomitant aripiprazole and gabapentin use; consider starting gabapentin at a low dose. Concomitant use increases the risk for additive CNS depression.
Ganirelix: (Moderate) Antipsychotic-induced hyperprolactinemia results in down-regulation of the number of pituitary GnRH receptors and may interfere with the response to ganirelix, a gonadotropin-releasing hormone (GnRH) analog.
Gefitinib: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of gefitinib. Patients receiving both a CYP3A inhibitor plus gefitinib may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; gefitinib is a weak CYP2D6 inhibitor.
Gemifloxacin: (Moderate) Concomitant use of aripiprazole and gemifloxacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Gemtuzumab Ozogamicin: (Moderate) Concomitant use of aripiprazole and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Gilteritinib: (Moderate) Concomitant use of aripiprazole and gilteritinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Givosiran: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of givosiran. Patients receiving both a CYP3A inhibitor plus givosiran may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; givosiran is a moderate CYP2D6 inhibitor.
Glasdegib: (Major) Avoid coadministration of glasdegib with aripiprazole due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
Glipizide; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Glyburide; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Goserelin: (Moderate) Concomitant use of aripiprazole and androgen deprivation therapy (i.e., goserelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Granisetron: (Moderate) Concomitant use of aripiprazole and granisetron may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Grapefruit juice: (Major) Advise patients to avoid grapefruit and grapefruit juice during aripiprazole treatment due to the risk of increased aripiprazole exposure and adverse reactions. Aripiprazole is a CYP2D6 and CYP3A substrate and grapefruit juice is a moderate CYP2D6 and strong CYP3A inhibitor.
Guaifenesin; Hydrocodone: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Halogenated Anesthetics: (Major) Concomitant use of aripiprazole and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Haloperidol: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of haloperidol. Patients receiving both a CYP3A inhibitor plus haloperidol may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Additionally, consider taking steps to minimize the risk of QT/QTc interval prolongation and torsade de pointes (TdP), such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Concomitant use may increase the risk for CNS depression, QT prolongation and torsade de pointes (TdP), and may increase aripiprazole exposure and the risk for other aripiprazole-related adverse effects. Aripiprazole is a CYP2D6 and CYP3A substrate; haloperidol is a weak CYP2D6 inhibitor. Both medications have been associated with QT prolongation. The intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Histrelin: (Moderate) Concomitant use of aripiprazole and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Homatropine; Hydrocodone: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydralazine: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Hydralazine; Isosorbide Dinitrate, ISDN: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Hydrocodone: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking aripiprazole Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydromorphone: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydroxychloroquine: (Major) Concomitant use of hydroxychloroquine and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Moderate) Concomitant use of aripiprazole and hydroxyzine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Also, monitor for unusual drowsiness and sedation during coadministration due to the risk for additive CNS depression.
Ibuprofen; Famotidine: (Minor) Coadministration of aripiprazole with famotidine decreases aripiprazole's solubility and rate of absorption. The Cmax of aripiprazole and the metabolite dehydroaripiprazole are decreased by 37% and 21%, respectively, and the AUC of aripiprazole and the dehydroaripiprazole metabolite are decreased by 13% and 15%, respectively. This interaction does not appear to cause clinically relevant effects and therefore no dosage adjustments are required.
Ibuprofen; Oxycodone: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Ibutilide: (Major) Concomitant use of ibutilide and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Idelalisib: (Major) Recommendations for managing aripiprazole and idelalisib vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; idelalisib is a strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and idelalisib vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; idelalisib is a strong CYP3A inhibitor.
Iloperidone: (Major) QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Iloperidone is an atypical antipsychotics with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with aripiprazole. In addition, caution is advisable when aripiprazole is given in combination with other CNS depressants such as other atypical antipsychotics. The risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, tardive dyskinesia, or seizures may be increased during combined use; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is deemed necessary. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent.
Iloprost: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Imatinib: (Major) Recommendations for managing aripiprazole and imatinib vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; imatinib is a weak CYP2D6 and moderate CYP3A inhibitor.
Imipramine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of aripiprazole and tricyclic antidepressants due to the risk for additive CNS depression.
Incretin Mimetics: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Indinavir: (Major) Recommendations for managing aripiprazole and indinavir vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a strong CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; indinavir is a weak CYP2D6 and strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and indinavir vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a strong CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; indinavir is a weak CYP2D6 and strong CYP3A inhibitor.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with aripiprazole due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
Insulin Degludec; Liraglutide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Insulin Glargine; Lixisenatide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Insulins: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and insulin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Isavuconazonium: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of isavuconazonium. Patients receiving both a CYP2D6 inhibitor plus isavuconazonium may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; isavuconazonium is a moderate CYP3A inhibitor.
Isoniazid, INH: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of isoniazid. Patients receiving both a CYP2D6 inhibitor plus isoniazid may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; isoniazid is a weak CYP3A inhibitor.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Recommendations for managing aripiprazole and rifampin vary by aripiprazole dosage form. For aripiprazole oral dosage forms, double the usual dose over 1 to 2 weeks. For extended-release aripiprazole injections administered monthly (Abilify Maintena) and every 2 months (Abilify Asimtufii), avoid concomitant use. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; rifampin is a strong CYP3A inducer. (Major) Recommendations for managing aripiprazole and rifampin vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), increase the 441 mg dose to 662 mg; no adjustments are necessary for other dosages. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; rifampin is a strong CYP3A inducer. (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of isoniazid. Patients receiving both a CYP2D6 inhibitor plus isoniazid may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; isoniazid is a weak CYP3A inhibitor.
Isoniazid, INH; Rifampin: (Major) Recommendations for managing aripiprazole and rifampin vary by aripiprazole dosage form. For aripiprazole oral dosage forms, double the usual dose over 1 to 2 weeks. For extended-release aripiprazole injections administered monthly (Abilify Maintena) and every 2 months (Abilify Asimtufii), avoid concomitant use. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; rifampin is a strong CYP3A inducer. (Major) Recommendations for managing aripiprazole and rifampin vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), increase the 441 mg dose to 662 mg; no adjustments are necessary for other dosages. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; rifampin is a strong CYP3A inducer. (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of isoniazid. Patients receiving both a CYP2D6 inhibitor plus isoniazid may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; isoniazid is a weak CYP3A inhibitor.
Isradipine: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Istradefylline: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of istradefylline. Patients receiving both a CYP2D6 inhibitor plus istradefylline may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; istradefylline is a weak CYP3A inhibitor.
Itraconazole: (Contraindicated) Avoid concomitant use of aripiprazole and itraconazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use also increases aripiprazole exposure and risk for side effects. If concomitant use is necessary, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, itraconazole is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Contraindicated) Avoid concomitant use of aripiprazole and itraconazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use also increases aripiprazole exposure and risk for side effects. If concomitant use is necessary, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate, itraconazole is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation.
Ivacaftor: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of ivacaftor. Patients receiving both a CYP2D6 inhibitor plus ivacaftor may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; ivacaftor is a weak CYP3A inhibitor.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with aripiprazole due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
Ketoconazole: (Contraindicated) Avoid concomitant use of aripiprazole and ketoconazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use also increases aripiprazole exposure and risk for side effects. If concomitant use is necessary, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, ketoconazole is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Contraindicated) Avoid concomitant use of aripiprazole and ketoconazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use also increases aripiprazole exposure and risk for side effects. If concomitant use is necessary, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate, ketoconazole is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation.
Labetalol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Lamotrigine: (Minor) Coadministration of aripiprazole and lamotrigine may slightly decrease lamotrigine plasma concentrations; however, this interaction is not expected to be clinically meaningful. During clinical trials, lamotrigine exposure was reduced approximately 10% in patients (n = 18) on a stable regimen of lamotrigine 100 mg/day to 400 mg/day who received ariprazole 10 mg/day to 30 mg/day for 7 days, followed by 30 mg/day for an additional 7 days.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Concomitant use of aripiprazole and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, clarithromycin is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Major) Concomitant use of aripiprazole and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, clarithromycin is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation.
Lapatinib: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of lapatinib. Patients receiving both a CYP2D6 inhibitor plus lapatinib may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Additionally, concomitant use may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Aripiprazole is a CYP3A and CYP2D6 substrate; lapatinib is a weak CYP3A inhibitor. Both medications have been associated with QT prolongation.
Larotrectinib: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of larotrectinib. Patients receiving both a CYP2D6 inhibitor plus larotrectinib may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; larotrectinib is a weak CYP3A inhibitor.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and aripiprazole. Concurrent use may result in additive CNS depression.
Lefamulin: (Major) Concomitant use of aripiprazole and lefamulin increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, monitor for aripiprazole-related adverse reactions during concomitant use of oral lefamulin. Patients receiving both a CYP2D6 inhibitor plus oral lefamulin may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, oral lefamulin is a moderate CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atypical antipsyhotics. Dosage adjustments of lemborexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Lenacapavir: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of lenacapavir. Patients receiving both a CYP2D6 inhibitor plus lenacapavir may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; lenacapavir is a moderate CYP3A inhibitor.
Lenvatinib: (Major) Concomitant use of lenvatinib and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Letermovir: (Moderate) Because aripiprazole is partially metabolized by CYP3A4, patients should be carefully monitored for aripiprazole-related adverse reactions during concurrent use of a moderate CYP3A4 inhibitor such as letermovir. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP2D6, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adults receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inhibitor. During coadministration of letermovir and cyclosporine, letermovir may exhibit more potent CYP3A4 inhibitory properties. When letermovir and cyclosporine are used concurrently with aripiprazole, consult the aripiprazole product information for dosage adjustments of aripiprazole necessary during use of a potent CYP3A4 inhibitor.
Leuprolide: (Moderate) Concomitant use of aripiprazole and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Leuprolide; Norethindrone: (Moderate) Concomitant use of aripiprazole and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Levamlodipine: (Moderate) Monitor for aripiprazole-related adverse reactions and hypotension during concomitant use of amlodipine. Patients receiving both a CYP2D6 inhibitor plus amlodipine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Additionally, aripiprazole may enhance the hypotensive effects of antihypertensive agents such as amlodipine. Aripiprazole is a CYP3A and CYP2D6 substrate; amlodipine is a weak CYP3A inhibitor.
Levobunolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Levocetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Levodopa: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Levofloxacin: (Moderate) Levofloxacin should be used cautiously with other agents that may prolong the QT interval or increase the risk of torsade de pointes (TdP). Levofloxacin has been associated with a risk of QT prolongation and TdP. Although extremely rare, TdP has been reported during postmarketing surveillance of levofloxacin. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
Levoketoconazole: (Contraindicated) Avoid concomitant use of aripiprazole and ketoconazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use also increases aripiprazole exposure and risk for side effects. If concomitant use is necessary, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, ketoconazole is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Contraindicated) Avoid concomitant use of aripiprazole and ketoconazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use also increases aripiprazole exposure and risk for side effects. If concomitant use is necessary, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate, ketoconazole is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation.
Levorphanol: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Linagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Liraglutide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Lithium: (Moderate) Concomitant use of aripiprazole and lithium may increase the risk of neuroleptic malignant syndrome (NMS) and QT/QTc prolongation and torsade de pointes (TdP) in some patients. Monitor for neurotoxicity during concomitant use and consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. NMS has been observed during concurrent use of lithium and antipsychotics.
Lixisenatide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Lofexidine: (Moderate) Monitor ECG and for hypotension if lofexidine is coadministered with aripiprazole due to the potential for additive QT prolongation and effects on blood pressure. Due to its alpha adrenergic antagonism, aripiprazole has the potential to enhance the effect of lofexidine on blood pressure. Lofexidine may also cause additive sedation with CNS depressants, such as the atypical antipsychotics. Lofexidine prolongs the QT interval, and torsade de pointes (TdP) has been reported during postmarketing use. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Patients being given lofexidine in an outpatient setting should be capable of and instructed on self-monitoring for hypotension, orthostasis, bradycardia, and associated symptoms. If clinically significant or symptomatic hypotension and/or bradycardia occur, the next dose of lofexidine should be reduced in amount, delayed, or skipped.
Lonafarnib: (Major) Recommendations for managing aripiprazole and lonafarnib vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; lonafarnib is a strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and lonafarnib vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; lonafarnib is a strong CYP3A inhibitor.
Loop diuretics: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Loperamide: (Moderate) Concomitant use of loperamide and aripiprazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Loperamide; Simethicone: (Moderate) Concomitant use of loperamide and aripiprazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Lopinavir; Ritonavir: (Major) Concomitant use of lopinavir and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Major) Recommendations for managing aripiprazole and ritonavir vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a strong CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; ritonavir is a weak CYP2D6 and strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and ritonavir vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a strong CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; ritonavir is a weak CYP2D6 and strong CYP3A inhibitor.
Lorazepam: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
Lorcaserin: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of lorcaserin. Patients receiving both a CYP3A inhibitor plus lorcaserin may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; lorcaserin is a weak CYP2D6 inhibitor.
Loxapine: (Major) Caution is advisable during concurrent use of aripiprazole with other CNS depressants such as loxapine. The risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, or seizures may be increased during combined use; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is deemed necessary. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Lumacaftor; Ivacaftor: (Major) Recommendations for managing aripiprazole and lumacaftor; ivacaftor vary by aripiprazole dosage form. For aripiprazole oral dosage forms, double the usual dose over 1 to 2 weeks. For extended-release aripiprazole injections administered monthly (Abilify Maintena) and every 2 months (Abilify Asimtufii), avoid concomitant use. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; lumacaftor; ivacaftor is a strong CYP3A inducer. (Major) Recommendations for managing aripiprazole and lumacaftor; ivacaftor vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), increase the 441 mg dose to 662 mg; no adjustments are necessary for other dosages. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; lumacaftor; ivacaftor is a strong CYP3A inducer.
Lumacaftor; Ivacaftor: (Major) Recommendations for managing aripiprazole and lumacaftor; ivacaftor vary by aripiprazole dosage form. For aripiprazole oral dosage forms, double the usual dose over 1 to 2 weeks. For extended-release aripiprazole injections administered monthly (Abilify Maintena) and every 2 months (Abilify Asimtufii), avoid concomitant use. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; lumacaftor; ivacaftor is a strong CYP3A inducer. (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of ivacaftor. Patients receiving both a CYP2D6 inhibitor plus ivacaftor may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; ivacaftor is a weak CYP3A inhibitor.
Lumateperone: (Moderate) Coadministration of antipsychotics, such as lumateperone and aripiprazole, may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from antipsychotic combinations has not been established and data are very limited, the risk may be increased during combined use versus use of an antipsychotic alone.
Lurasidone: (Moderate) Monitor for adverse effects including excessive sedation, somnolence, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures during coadministration of lurasidone and aripiprazole. The risk of these adverse effects may be increased during concurrent use. Lower dosages may be necessary if combination therapy is deemed necessary.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as aripiprazole. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
Maprotiline: (Major) QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Aripiprazole should be used cautiously with maprotiline.
Maribavir: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of maribavir. Patients receiving both a CYP2D6 inhibitor plus maribavir may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; maribavir is a weak CYP3A inhibitor.
Mecamylamine: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Meclizine: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Mefloquine: (Moderate) Concomitant use of aripiprazole and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Meglitinides: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Meperidine: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Meprobamate: (Moderate) The CNS-depressant effects of meprobamate can be potentiated with concomitant administration of other drugs known to cause CNS depression including antipsychotics.
Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Metformin; Repaglinide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Metformin; Rosiglitazone: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Metformin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Metformin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Methadone: (Major) Aripiprazole should be used cautiously and with close monitoring with methadone due to the potential for increased risk of QT prolongation, torsade de pointes (TdP), and additive CNS depressant effects. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and QT prolongation. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Methadone is considered to be associated with an increased risk for QT prolongation and torsade de pointes (TdP), especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). Laboratory studies, both in vivo and in vitro, have demonstrated that methadone inhibits cardiac potassium channels and prolongs the QT interval. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction.
Methohexital: (Major) Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. Additive CNS effects are possible, including drowsiness or dizziness. Patients should report any unusual changes in moods or behaviors while taking this combination.
Metoclopramide: (Contraindicated) Avoid metoclopramide in patients receiving atypical antipsychotics. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia.
Metoprolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Metoprolol; Hydrochlorothiazide, HCTZ: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Metronidazole: (Moderate) Concomitant use of metronidazole and aripiprazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Midazolam: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
Midostaurin: (Major) Concomitant use of midostaurin and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mifepristone: (Major) Concomitant use of aripiprazole and mifepristone increases the risk of QT/QT c prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, mifepristone is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Major) Concomitant use of aripiprazole and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, mifepristone is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation.
Miglitol: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Minoxidil: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Mirabegron: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of mirabegron. Patients receiving both a CYP3A inhibitor plus mirabegron may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; mirabegron is a moderate CYP2D6 inhibitor.
Mirtazapine: (Moderate) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and aripiprazole. Coadminister with caution. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine, primarily following overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation.
Mitotane: (Major) Recommendations for managing aripiprazole and mitotane vary by aripiprazole dosage form. For aripiprazole oral dosage forms, double the usual dose over 1 to 2 weeks. For extended-release aripiprazole injections administered monthly (Abilify Maintena) and every 2 months (Abilify Asimtufii), avoid concomitant use. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; mitotane is a strong CYP3A inducer. (Major) Recommendations for managing aripiprazole and mitotane vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), increase the 441 mg dose to 662 mg; no adjustments are necessary for other dosages. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; mitotane is a strong CYP3A inducer.
Mobocertinib: (Major) Concomitant use of mobocertinib and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Modafinil: (Moderate) Because aripiprazole is metabolized by CYP3A4, concurrent use of CYP3A4 inducers such as modafinil may result in decreased plasma concentrations of aripiprazole. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. An increase in aripiprazole dosage may be clinically warranted in some patients. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
Molindone: (Major) Close monitoring is advisable during concurrent use of molindone with other antipsychotics. Because molindone shares certain pharmacological properties with other antipsychotics, additive cardiac effects (e.g., hypotension), CNS effects (e.g., drowsiness), or anticholinergic effects (e.g., constipation, xerostomia) may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Monoamine oxidase inhibitors: (Major) Avoid concomitant use, or use in rapid succession, of monoamine oxidase inhibitors (MAOIs) and aripiprazole. If concomitant use is necessary, monitor for signs and symptoms of serotonin syndrome, blood pressure, and for unusual drowsiness and sedation. Concomitant use increases the risk for serotonin syndrome and additive hypotension and CNS depression. If serotonin syndrome occurs, discontinue therapy.
Morphine: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Morphine; Naltrexone: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Moxifloxacin: (Major) Concomitant use of aripiprazole and moxifloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Nabilone: (Moderate) Drugs that can cause CNS depression, if used concomitantly with atypical antipsychotics, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
Nadolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Nafarelin: (Moderate) Antipsychotics may cause hyperprolactinemia and should not be administered concomitantly with nafarelin since hyperprolactinemia down-regulates the number of pituitary GnRH receptors.
Nalbuphine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and nalbuphine. Concurrent use may result in additive CNS depression.
Nateglinide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Nebivolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Nebivolol; Valsartan: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Nefazodone: (Major) Recommendations for managing aripiprazole and nefazodone vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; nefazodone is a strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and nefazodone vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; nefazodone is a strong CYP3A inhibitor.
Nelfinavir: (Major) Recommendations for managing aripiprazole and nelfinavir vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; nelfinavir is a strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and nelfinavir vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; nelfinavir is a strong CYP3A inhibitor.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of netupitant. Patients receiving both a CYP2D6 inhibitor plus netupitant may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; netupitant is a moderate CYP3A inhibitor.
Nevirapine: (Moderate) Monitor for decreased efficacy of aripiprazole if coadministration with nevirapine is necessary; a dose adjustment may be needed. Concomitant use may decrease aripiprazole exposure. Aripiprazole is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Nicardipine: (Major) Because aripiprazole is metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the oral aripiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving inhibitors of both CYP3A4 and CYP2D6 such as nicardipine. Adult patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 and CYP2D6 inhibitor. Lastly, aripiprazole may enhance the hypotensive effects of antihypertensive agents such as nicardipine.
Nifedipine: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Nilotinib: (Major) Avoid concomitant use aripiprazole and nilotinib, if possible, especially in patients with risk factors for torsade de pointes (TdP). If concomitant use is necessary, patients receiving both a CYP2D6 inhibitor plus nilotinib may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. Additionally, consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Concomitant use increases the risk for QT/QTc prolongation and TdP and may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate, nilotinib is a moderate CYP3A inhibitor, and both medications have been associated with QT interval prolongation.
Niraparib; Abiraterone: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of abiraterone. Patients receiving both a CYP3A inhibitor plus abiraterone may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; abiraterone is a moderate CYP2D6 inhibitor.
Nirmatrelvir; Ritonavir: (Major) Recommendations for managing aripiprazole and ritonavir vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a strong CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; ritonavir is a weak CYP2D6 and strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and ritonavir vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a strong CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; ritonavir is a weak CYP2D6 and strong CYP3A inhibitor.
Nisoldipine: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Nitroprusside: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Non-Ionic Contrast Media: (Major) Aripiprazole lowers the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Nortriptyline: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of aripiprazole and tricyclic antidepressants due to the risk for additive CNS depression.
Ofloxacin: (Moderate) Ofloxacin should be used cautiously with other agents, such as aripiprazole, that may prolong the QT interval or increase the risk of torsade de pointes (TdP). QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Quinolones have been associated with a risk of QT prolongation and TdP. Although extremely rare, TdP has been reported during postmarketing surveillance of ofloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
Olanzapine: (Moderate) Coadministration may result in additive effects on the QT interval. Both aripiprazole and olanzapine have been associated with QT prolongation. In addition, the risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, tardive dyskinesia, or seizures may be increased during combined use; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is deemed necessary.
Olanzapine; Fluoxetine: (Major) Reduce the oral aripiprazole dosage by one-half of the usual dose in patients receiving strong CYP2D6 inhibitors such as fluoxetine. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP3A4 inhibitor, as aripiprazole is also metabolized by CYP3A4. Addtionally, aripiprazole and fluoxetine are both associated with prolongation of the QT interval; caution and close monitoring are recommended. Avoid concurrent use of Aristada Initio and fluoxetine because the dose of Aristada Initio cannot be modified. For other long-active aripiprazole injectables (e.g., Ability Maintena, Aristada), dose adjustments are recommended with strong CYP2D6 inhibitors and combined strong CYP2D6/CYP3A4 inhibitors; the recommendations are dependent on the aripiprazole IM depot dosage, the product given, and the duration of the concomitant inhibitors as specified in the product labels. (Moderate) Coadministration may result in additive effects on the QT interval. Both aripiprazole and olanzapine have been associated with QT prolongation. In addition, the risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, tardive dyskinesia, or seizures may be increased during combined use; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is deemed necessary.
Olanzapine; Samidorphan: (Moderate) Coadministration may result in additive effects on the QT interval. Both aripiprazole and olanzapine have been associated with QT prolongation. In addition, the risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, tardive dyskinesia, or seizures may be increased during combined use; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is deemed necessary.
Oliceridine: (Moderate) Concomitant use of oliceridine with aripiprazole may cause excessive sedation and somnolence. Limit the use of oliceridine with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for aripiprazole-related adverse reactions and hypotension during concomitant use of amlodipine. Patients receiving both a CYP2D6 inhibitor plus amlodipine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Additionally, aripiprazole may enhance the hypotensive effects of antihypertensive agents such as amlodipine. Aripiprazole is a CYP3A and CYP2D6 substrate; amlodipine is a weak CYP3A inhibitor.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Because aripiprazole is partially metabolized by CYP3A4, caution is advisable during coadministration of a CYP3A4 inducer, such as rifabutin. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. A dose adjustment of aripiprazole may be needed. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
Ondansetron: (Major) If ondansetron and aripiprazole must be coadministered, ECG monitoring is recommended. Ondansetron has been associated with a dose-related increase in the QT interval and postmarketing reports of torsade de pointes (TdP). QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
Opicapone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or COMT inhibitor during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and COMT inhibitors may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with COMT inhibitors and other Parkinson's treatments than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Oritavancin: (Moderate) Aripiprazole is metabolized by CYP3A4 and CYP2D6; oritavancin is a weak CYP3A4 and CYP2D6 inducer. Plasma concentrations and efficacy of aripiprazole may be reduced if these drugs are administered concurrently. An increase in aripiprazole dosage may be clinically warranted in some patients. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 and CYP2D6 inducer.
Osilodrostat: (Major) Concomitant use of aripiprazole and osilodrostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients and increases aripiprazole exposure and risk for side effects. An aripiprazole dosage reduction is necessary; management recommendations vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. Additionally, consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Aripiprazole is CYP2D6 and CYP3A substrate, osilodrostat is a weak CYP2D6 and CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Moderate) Concomitant use of aripiprazole and osilodrostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Osimertinib: (Major) Concomitant use of osimertinib and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Oxaliplatin: (Major) Concomitant use of oxaliplatin and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Oxazepam: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
Oxcarbazepine: (Moderate) Because aripiprazole is partially metabolized by CYP3A4, caution is advisable during use of a CYP3A4 inducer such as oxcarbazepine. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. A dose adjustment of aripiprazole may be needed. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
Oxycodone: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Oxymorphone: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking aripiprazole due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
Pacritinib: (Major) Avoid concomitant use of aripiprazole and pacritinib, if possible, especially in patients with risk factors for torsade de pointes (TdP). If use is necessary, patients receiving both a CYP2D6 inhibitor plus pacritinib may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Additionally, monitor for aripiprazole-related adverse effects and consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Concomitant use may increase aripiprazole exposure and risk for QT prolongation and TdP. Aripiprazole is a CYP3A and CYP2D6 substrate, pacritinib is a weak CYP3A inhibitor, and both medications have been associated with QT prolongation.
Palbociclib: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of palbociclib. Patients receiving both a CYP2D6 inhibitor plus palbociclib may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; palbociclib is a weak CYP3A inhibitor.
Paliperidone: (Major) Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. If coadministration is considered necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential. In addition, the risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, tardive dyskinesia, or seizures may be increased during combined use of antipsychotics; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is necessary.
Panobinostat: (Major) Avoid concomitant use of aripiprazole and panobinostat, if possible, especially in patients with risk factors for torsade de pointes (TdP). If use is necessary in patients who are receiving both a CYP3A inhibitor plus panobinostat, an aripiprazole dosage reduction may be required. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Additionally, monitor for aripiprazole-related adverse effects and consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Concomitant use may increase aripiprazole exposure and risk for QT prolongation and TdP. Aripiprazole is a CYP2D6 and CYP3A substrate, panobinostat is a moderate CYP2D6 inhibitor, and both medications have been associated with QT prolongation.
Paroxetine: (Major) Recommendations for managing aripiprazole and paroxetine vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer half of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg. Further dosage reductions may be required in patients who are also receiving a CYP3A inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; paroxetine is a strong CYP2D6 inhibitor. (Major) Recommendations for managing aripiprazole and paroxetine vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg or for patients known to be poor metabolizers of CYP2D6. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP3A inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; paroxetine is a strong CYP2D6 inhibitor.
Pasireotide: (Moderate) Concomitant use of aripiprazole and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Pazopanib: (Major) Concomitant use of aripiprazole and pazopanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. Aripiprazole is CYP2D6 and CYP3A substrate, pazopanib is a weak CYP2D6 and CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Major) Concomitant use of aripiprazole and pazopanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Peginterferon Alfa-2b: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of peginterferon alfa-2b. Patients receiving both a CYP3A inhibitor plus peginterferon alfa-2b may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; peginterferon alfa-2b is a weak CYP2D6 inhibitor.
Pentamidine: (Major) Concomitant use of pentamidine and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pentazocine: (Moderate) Coadministration of pentazocine with atypical antipsychotics may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation. Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity.
Pentazocine; Naloxone: (Moderate) Coadministration of pentazocine with atypical antipsychotics may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation. Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity.
Pentobarbital: (Major) Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. Additive CNS effects are possible, including drowsiness or dizziness. Patients should report any unusual changes in moods or behaviors while taking this combination.
Perindopril; Amlodipine: (Moderate) Monitor for aripiprazole-related adverse reactions and hypotension during concomitant use of amlodipine. Patients receiving both a CYP2D6 inhibitor plus amlodipine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Additionally, aripiprazole may enhance the hypotensive effects of antihypertensive agents such as amlodipine. Aripiprazole is a CYP3A and CYP2D6 substrate; amlodipine is a weak CYP3A inhibitor.
Perphenazine: (Major) Coadministration may result in additive effects on the QT interval. Both perphenazine and aripiprazole have been associated with QT prolongation; concurrent use may increase this risk. Additionally, increased aripiprazole blood levels may occur when it is coadministered with an inhibitor of CYP2D6, such as perphenazine. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adults receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP2D6 inhibitor. Coadministration of perphenazine with atypical agents may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Perphenazine; Amitriptyline: (Major) Coadministration may result in additive effects on the QT interval. Both perphenazine and aripiprazole have been associated with QT prolongation; concurrent use may increase this risk. Additionally, increased aripiprazole blood levels may occur when it is coadministered with an inhibitor of CYP2D6, such as perphenazine. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adults receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP2D6 inhibitor. Coadministration of perphenazine with atypical agents may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. (Moderate) Monitor for unusual drowsiness and sedation during coadministration of aripiprazole and tricyclic antidepressants due to the risk for additive CNS depression.
Phenobarbital: (Major) Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. Additive CNS effects are possible, including drowsiness or dizziness. Patients should report any unusual changes in moods or behaviors while taking this combination.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. Additive CNS effects are possible, including drowsiness or dizziness. Patients should report any unusual changes in moods or behaviors while taking this combination.
Phenoxybenzamine: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Phentermine; Topiramate: (Moderate) Monitor for unusal drowsiness and excessive sedation during concomitant aripiprazole and topiramate use due to the risk for additive CNS depression.
Phentolamine: (Moderate) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Phenytoin: (Major) Recommendations for managing aripiprazole and phenytoin/fosphenytoin vary by aripiprazole dosage form. For aripiprazole oral dosage forms, double the usual dose over 1 to 2 weeks. For extended-release aripiprazole injections administered monthly (Abilify Maintena) and every 2 months (Abilify Asimtufii), avoid concomitant use. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; phenytoin/fosphenytoin is a strong CYP3A inducer. (Major) Recommendations for managing aripiprazole and phenytoin/fosphenytoin vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), increase the 441 mg dose to 662 mg; no adjustments are necessary for other dosages. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; phenytoin/fosphenytoin are strong CYP3A inducers.
Pimavanserin: (Major) Concomitant use of pimavanserin and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pimozide: (Contraindicated) Avoid concomitant use of aripiprazole and pimozide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. If use is necessary in patients receiving both a CYP3A inhibitor plus pimozide, an aripiprazole dosage adjustment may be required. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects; use may also increase the risk for QT/QTc prolongation and TdP. Aripiprazole is a CYP2D6 and CYP3A substrate, pimozide is a weak CYP2D6 inhibitor, and both medications have been associated with QT/QTc prolongation.
Pindolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Pioglitazone: (Moderate) Monitor blood glucose during concomitant aripiprazole and pioglitazone use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Pioglitazone; Glimepiride: (Moderate) Monitor blood glucose during concomitant aripiprazole and pioglitazone use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Pioglitazone; Metformin: (Moderate) Monitor blood glucose during concomitant aripiprazole and pioglitazone use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Pirtobrutinib: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of pirtobrutinib. Patients receiving both a CYP2D6 inhibitor plus pirtobrutinib may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; pirtobrutinib is a weak CYP3A inhibitor.
Pitolisant: (Major) Concomitant use of pitolisant and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking aripiprazole due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
Posaconazole: (Contraindicated) Avoid concomitant use of aripiprazole and posaconazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use also increases aripiprazole exposure and risk for side effects. If concomitant use is necessary, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, posaconazole is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Contraindicated) Avoid concomitant use of aripiprazole and posaconazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use also increases aripiprazole exposure and risk for side effects. If concomitant use is necessary, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate, posaconazole is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation.
Pramipexole: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or pramipexole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and pramipexole may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with pramipexole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Pramlintide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Prazosin: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Pregabalin: (Moderate) Monitor for respiratory depression and sedation during concomitant aripiprazole and pregabalin use; consider starting pregabalin at a low dose. Concomitant use increases the risk for additive CNS depression.
Primaquine: (Moderate) Concomitant use of aripiprazole and primaquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Primidone: (Major) Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. Additive CNS effects are possible, including drowsiness or dizziness. Patients should report any unusual changes in moods or behaviors while taking this combination.
Procainamide: (Major) Concomitant use of procainamide and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Prochlorperazine: (Major) Prochlorperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Prochlorperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation, such as aripiprazole. Co-administration of prochlorperazine with other antipsychotics may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Promethazine: (Moderate) Concomitant use of aripiprazole and promethazine may increase the risk of CNS depression and QT/QTc prolongation and torsade de pointes (TdP) in some patients. Monitor for unusual drowsiness and excess sedation and consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Promethazine; Dextromethorphan: (Moderate) Concomitant use of aripiprazole and promethazine may increase the risk of CNS depression and QT/QTc prolongation and torsade de pointes (TdP) in some patients. Monitor for unusual drowsiness and excess sedation and consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Promethazine; Phenylephrine: (Moderate) Concomitant use of aripiprazole and promethazine may increase the risk of CNS depression and QT/QTc prolongation and torsade de pointes (TdP) in some patients. Monitor for unusual drowsiness and excess sedation and consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitorin g, especially in patients with additional risk factors for TdP.
Propafenone: (Major) Concomitant use of aripiprazole and propafenone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase aripiprazole exposure and other aripiprazole-related adverse effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. If concomitant use is necessary, monitor for aripiprazole-related adverse reactions and consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Patients receiving both a CYP3A inhibitor plus propafenone may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects; use may also increase the risk for QT/QTc prolongation and TdP. Aripiprazole is a CYP2D6 and CYP3A substrate, propafenone is a weak CYP2D6 inhibitor, and both medications have been associated with QT/QTc prolongation.
Propranolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Propranolol; Hydrochlorothiazide, HCTZ: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Protriptyline: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of aripiprazole and tricyclic antidepressants due to the risk for additive CNS depression.
Pseudoephedrine; Triprolidine: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Pyrilamine: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Quazepam: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
Quetiapine: (Major) Concomitant use of aripiprazole and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and additive CNS depression. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Monitor for unusual drowsiness and sedation during coadministration.
Quinidine: (Contraindicated) Avoid use of aripiprazole with quinidine unless the benefit outweighs the risk. Quinidine is generally contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6, such as aripiprazole, as the effects on the QT interval may be increased. Manufacturer recommendations for this combination have varied. Do not use the combination product of dextromethorphan; quinidine with aripiprazole. The manufacturers of aripiprazole products do not contraindicate use of quinidine, but recommend dosage adjustments of aripiprazole when used with potent CYP2D6 inhibitors, such as quinidine. For example, the oral aripiprazole dose should be reduced by 50%. Injectable forms of aripiprazole require dose adjustment when the potent CYP2D6 inhibitor will be used for more than 14 days. See the manufacturer prescribing information for detailed recommendations. Both aripiprazole and quinidine are associated with QT prolongation. Increased aripiprazole exposure is likely when a potent CYP2D6 inhibitor like quinidine is used concurrently. In one evaluation, concurrent use of quinidine and oral aripiprazole resulted in an increase in the AUC of aripiprazole of 112% and a decrease in the AUC of its active metabolite by 35%.
Quinine: (Major) Concomitant use of aripiprazole and quinine increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. Aripiprazole is CYP2D6 and CYP3A substrate, quinine is a moderate CYP2D6 and weak CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Major) Concomitant use of aripiprazole and quinine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quizartinib: (Major) Concomitant use of quizartinib and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ramelteon: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics.
Ranolazine: (Major) Concomitant use of aripiprazole and ranolazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients and increases aripiprazole exposure and risk for side effects. An aripiprazole dosage reduction is necessary; management recommendations vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. Additionally, consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Aripiprazole is CYP2D6 and CYP3A substrate, ranolazine is a moderate CYP2D6 and weak CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Moderate) Concomitant use of aripiprazole and ranolazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Rasagiline: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or rasagiline during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and rasagiline may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with rasagiline than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Relugolix: (Moderate) Concomitant use of aripiprazole and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) Concomitant use of aripiprazole and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Remifentanil: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Remimazolam: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
Repaglinide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Ribociclib: (Major) Concomitant use of aripiprazole and ribociclib increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, ribociclib is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Major) Concomitant use of aripiprazole and ribociclib increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, ribociclib is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation.
Ribociclib; Letrozole: (Major) Concomitant use of aripiprazole and ribociclib increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, ribociclib is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Major) Concomitant use of aripiprazole and ribociclib increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, ribociclib is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation.
Rifabutin: (Moderate) Because aripiprazole is partially metabolized by CYP3A4, caution is advisable during coadministration of a CYP3A4 inducer, such as rifabutin. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. A dose adjustment of aripiprazole may be needed. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
Rifampin: (Major) Recommendations for managing aripiprazole and rifampin vary by aripiprazole dosage form. For aripiprazole oral dosage forms, double the usual dose over 1 to 2 weeks. For extended-release aripiprazole injections administered monthly (Abilify Maintena) and every 2 months (Abilify Asimtufii), avoid concomitant use. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; rifampin is a strong CYP3A inducer. (Major) Recommendations for managing aripiprazole and rifampin vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), increase the 441 mg dose to 662 mg; no adjustments are necessary for other dosages. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; rifampin is a strong CYP3A inducer.
Rifapentine: (Major) Recommendations for managing aripiprazole and rifapentine vary by aripiprazole dosage form. For aripiprazole oral dosage forms, double the usual dose over 1 to 2 weeks. For extended-release aripiprazole injections administered monthly (Abilify Maintena) and every 2 months (Abilify Asimtufii), avoid concomitant use. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; rifapentine is a strong CYP3A inducer. (Major) Recommendations for managing aripiprazole and rifapentine vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), increase the 441 mg dose to 662 mg; no adjustments are necessary for other dosages. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; rifapentine is a strong CYP3A inducer.
Rilpivirine: (Moderate) Concomitant use of aripiprazole and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Risperidone: (Moderate) Use risperidone and aripiprazole together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
Ritlecitinib: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of ritlecitinib. Patients receiving both a CYP2D6 inhibitor plus ritlecitinib may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; ritlecitinib is a moderate CYP3A inhibitor.
Ritonavir: (Major) Recommendations for managing aripiprazole and ritonavir vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a strong CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; ritonavir is a weak CYP2D6 and strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and ritonavir vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a strong CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; ritonavir is a weak CYP2D6 and strong CYP3A inhibitor.
Rolapitant: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of rolapitant. Patients receiving both a CYP3A inhibitor plus rolapitant may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; rolapitant is a moderate CYP2D6 inhibitor.
Romidepsin: (Moderate) Concomitant use of aripiprazole and romidepsin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ropinirole: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or ropinirole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and ropinirole may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with ropinirole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Rosiglitazone: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Rotigotine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, excess sedation, and diminished effectiveness of the atypical antipsychotic or rotigotine during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and rotigotine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with rotigotine than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Rucaparib: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of rucaparib. Patients receiving both a CYP2D6 inhibitor plus rucaparib may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; rucaparib is a weak CYP3A inhibitor.
Safinamide: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or safinamide during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and safinamide may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with safinamide than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Saquinavir: (Major) Concomitant use of aripiprazole and saquinavir increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, saquinavir is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Major) Concomitant use of aripiprazole and saquinavir increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, saquinavir is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation.
Saxagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Secobarbital: (Major) Because aripiprazole is metabolized by CYP3A4, the manufacturer recommends that the oral aripiprazole dose be doubled over 1 to 2 weeks when strong CYP3A4 inducers, such as barbiturates, are added to aripiprazole therapy. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. When the CYP3A4 inducer is withdrawn from the combination therapy, the aripiprazole dose in adults should be reduced over 1 to 2 weeks to the original level. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. In adults receiving 662 mg, 882 mg, or 1,064 mg of Aristada and receiving a strong CYP3A4 inducer, no dosage adjustment is necessary; however, the 441 mg dose should be increased to 662 mg if the CYP inducer is added for more than 2 weeks. Avoid concurrent use of Aristada Initio and strong CYP3A4 inducers. Additive CNS effects are possible, including drowsiness or dizziness. Patients should report any unusual changes in moods or behaviors while taking this combination.
Selegiline: (Moderate) Monitor for loss of selegiline efficacy, signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, and unusual drowsiness and sedation during concomitant atypical antipsychotic and selegiline use. Dopamine antagonists, such as atypical antipsychotics, may diminish the effectiveness of selegiline. Concomitant use may increase the risk for serotonin syndrome or additive CNS depression. If serotonin syndrome occurs, discontinue therapy.
Selpercatinib: (Major) Concomitant use of aripiprazole and selpercatinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, monitor for aripiprazole-related adverse reactions during concomitant use. Patients receiving both a CYP2D6 inhibitor plus selpercatinib may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, selpercatinib is a weak CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation.
Semaglutide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Sertraline: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of sertraline and consider taking steps to minimize the risk of QT/QTc interval prolongation and torsade de pointes (TdP), such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Patients receiving both a CYP3A inhibitor plus sertraline may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects; use may also increase the risk for QT/QTc prolongation ad TdP. Aripiprazole is a CYP2D6 and CYP3A substrate, sertraline is a weak CYP2D6 inhibitor, and both medications have been associated with QT/QTc prolongation.
SGLT2 Inhibitors: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Siponimod: (Major) Concomitant use of siponimod and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sitagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and aripiprazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Solifenacin: (Moderate) Concomitant use of aripiprazole and solifenacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Sorafenib: (Major) Concomitant use of sorafenib and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sotagliflozin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Sotalol: (Major) Concomitant use of aripiprazole and sotalol increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Spironolactone: (Major) Monitor for aripiprazole-related adverse reactions during concurrent use of spironolactone. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP2D6 inhibitor. Adults receiving a combination of a CYP2D6 inhibitor and spironolactone for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inhibitor alone. Aripiprazole is a substrate for CYP2D6 and CYP3A4; spironolactone is a weak CYP3A4 inhibitor. Additionally, monitor blood pressure and adjust spironolactone dose accordingly as aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Spironolactone; Hydrochlorothiazide, HCTZ: (Major) Monitor for aripiprazole-related adverse reactions during concurrent use of spironolactone. Reduce the oral aripiprazole dosage to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response in patients also receiving a CYP2D6 inhibitor. Adults receiving a combination of a CYP2D6 inhibitor and spironolactone for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inhibitor alone. Aripiprazole is a substrate for CYP2D6 and CYP3A4; spironolactone is a weak CYP3A4 inhibitor. Additionally, monitor blood pressure and adjust spironolactone dose accordingly as aripiprazole may enhance the hypotensive effects of antihypertensive agents.
St. John's Wort, Hypericum perforatum: (Major) Recommendations for managing aripiprazole and St. John's wort vary by aripiprazole dosage form. For aripiprazole oral dosage forms, double the usual dose over 1 to 2 weeks. For extended-release aripiprazole injections administered monthly (Abilify Maintena) and every 2 months (Abilify Asimtufii), avoid concomitant use. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; St. John's wort is a strong CYP3A inducer. (Major) Recommendations for managing aripiprazole and St. John's wort vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), increase the 441 mg dose to 662 mg; no adjustments are necessary for other dosages. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Concomitant use may decrease aripiprazole exposure and reduce efficacy. Aripiprazole is CYP3A substrate; St. John's wort is a strong CYP3A inducer.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and aripiprazole. CNS depressants can potentiate the effects of stiripentol.
Streptogramins: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of quinupristin. Patients receiving both a CYP2D6 inhibitor plus quinupristin may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; quinupristin is a weak CYP3A inhibitor.
Sufentanil: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Sulfonylureas: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and sulfonylurea use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Sunitinib: (Moderate) Concomitant use of aripiprazole and sunitinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Suvorexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of suvorexant and atypical antipsyhotics. Dosage adjustments of suvorexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants.
Tacrolimus: (Moderate) Concomitant use of aripiprazole and tacrolimus may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tamoxifen: (Moderate) Concomitant use of aripiprazole and tamoxifen may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tapentadol: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Tasimelteon: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics.
Telavancin: (Moderate) Concomitant use of aripiprazole and telavancin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Telmisartan; Amlodipine: (Moderate) Monitor for aripiprazole-related adverse reactions and hypotension during concomitant use of amlodipine. Patients receiving both a CYP2D6 inhibitor plus amlodipine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Additionally, aripiprazole may enhance the hypotensive effects of antihypertensive agents such as amlodipine. Aripiprazole is a CYP3A and CYP2D6 substrate; amlodipine is a weak CYP3A inhibitor.
Temazepam: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
Terazosin: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Terbinafine: (Major) Recommendations for managing aripiprazole and terbinafine vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer half of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg. Further dosage reductions may be required in patients who are also receiving a CYP3A inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; terbinafine is a strong CYP2D6 inhibitor. (Major) Recommendations for managing aripiprazole and terbinafine vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg or for patients known to be poor metabolizers of CYP2D6. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP3A inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; terbinafine is a strong CYP2D6 inhibitor.
Tetrabenazine: (Major) Both tetrabenazine and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP). If possible, concurrent use of aripiprazole and tetrabenazine should be avoided since the risk of adverse effects such as QT prolongation, drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
Tezacaftor; Ivacaftor: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of ivacaftor. Patients receiving both a CYP2D6 inhibitor plus ivacaftor may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; ivacaftor is a weak CYP3A inhibitor.
Thiazide diuretics: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Thioridazine: (Contraindicated) Thioridazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP) and is contraindicated for use with other drugs that are known to prolong the QT interval. Other antipsychotics that may cause QT prolongation and TdP include aripiprazole. Also, coadministration of thioridazine with atypical antipsychotics may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Thiothixene: (Major) Caution is advisable during concurrent use of aripiprazole with other CNS depressants such as thiothixene. The risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, or seizures may be increased during combined use; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is deemed necessary. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Ticagrelor: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of ticagrelor. Patients receiving both a CYP2D6 inhibitor plus ticagrelor may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; ticagrelor is a weak CYP3A inhibitor.
Timolol: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents. It may be advisable to monitor blood pressure when these medications are coadministered.
Tipranavir: (Major) Recommendations for managing aripiprazole and tipranavir vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), avoid concomitant use. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; tipranavir is a strong CYP2D6 and strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and tipranavir vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), no dosage adjustment is necessary for patients already tolerating 441 mg; avoid use in patients taking higher doses. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; tipranavir is a strong CYP2D6 and strong CYP3A inhibitor.
Tirzepatide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Tizanidine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of aripiprazole and tizanidine due to the risk for additive CNS depression.
Tolcapone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or COMT inhibitor during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and COMT inhibitors may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with COMT inhibitors and other Parkinson's treatments than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Tolterodine: (Moderate) Caution is advised when administering aripiprazole with tolterodine, as use of these drugs together may increase the risk for QT prolongation and torsade de pointes (TdP). Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. QT prolongation has also occurred during therapeutic use of aripiprazole and following overdose.
Topiramate: (Moderate) Monitor for unusal drowsiness and excessive sedation during concomitant aripiprazole and topiramate use due to the risk for additive CNS depression.
Toremifene: (Major) Concomitant use of toremifene and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Tramadol: (Major) Reserve concomitant use of tramadol and aripiprazole for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation as well as seizures. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, seizures, and death.
Tramadol; Acetaminophen: (Major) Reserve concomitant use of tramadol and aripiprazole for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation as well as seizures. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, seizures, and death.
Trandolapril; Verapamil: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of verapamil. Patients receiving both a CYP2D6 inhibitor plus verapamil may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; verapamil is a moderate CYP3A inhibitor.
Trazodone: (Major) QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are postmarketing reports of torsade de pointes (TdP). Therefore, the manufacturer recommends avoiding trazodone in patients receiving other drugs that increase the QT interval.
Treprostinil: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Triamterene: (Moderate) Monitor blood pressure during concurrent use of triamterene; a triamterene dose adjustment may be needed. Due to its alpha-adrenergic antagonism, aripiprazole has the potential to enhance the effect of certain antihypertensive agents.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concurrent use of triamterene; a triamterene dose adjustment may be needed. Due to its alpha-adrenergic antagonism, aripiprazole has the potential to enhance the effect of certain antihypertensive agents.
Triazolam: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Intensity of sedation and orthostatic hypotension were greater with the combination of oral aripiprazole and lorazepam compared to aripiprazole alone.
Triclabendazole: (Moderate) Concomitant use of triclabendazole and aripiprazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tricyclic antidepressants: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of aripiprazole and tricyclic antidepressants due to the risk for additive CNS depression.
Trifluoperazine: (Moderate) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Trifluoperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation, such as aripiprazole. Co-administration of trifluoperazine with atypical agents (e.g., lurasidone and others) may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Trimipramine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of aripiprazole and tricyclic antidepressants due to the risk for additive CNS depression.
Triprolidine: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Triptorelin: (Moderate) Concomitant use of aripiprazole and androgen deprivation therapy (i.e., triptorelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Trofinetide: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of trofinetide. Patients receiving both a CYP2D6 inhibitor plus trofinetide may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; trofinetide is a weak CYP3A inhibitor.
Tucatinib: (Major) Recommendations for managing aripiprazole and tucatinib vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; tucatinib is a strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and tucatinib vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; tucatinib is a strong CYP3A inhibitor.
Valproic Acid, Divalproex Sodium: (Minor) When administered with valproic acid the Cmax of aripiprazole is decreased by 25%. This interaction does not appear to cause clinically relevant effects and therefore no dosage adjustments are required.
Vandetanib: (Major) Concomitant use of vandetanib and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vardenafil: (Moderate) Concomitant use of vardenafil and aripiprazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Vemurafenib: (Major) Because both vemurafenib and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, concomitant use of vemurafenib and aripiprazole may result in altered concentrations of aripiprazole. Vemurafenib is a weak inhibitor of CYP2D6 and an inducer of CYP3A4. Aripiprazole is a substrate of CYP2D6 and CYP3A4. Use caution and monitor patients for toxicity and efficacy.
Venlafaxine: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of venlafaxine and consider taking steps to minimize the risk of QT/QTc interval prolongation and torsade de pointes (TdP), such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Patients receiving both a CYP3A inhibitor plus venlafaxine may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects; use may also increase the risk for QT/QTc prolongation ad TdP. Aripiprazole is a CYP2D6 and CYP3A substrate, venlafaxine is a weak CYP2D6 inhibitor, and both medications have been associated with QT/QTc prolongation.
Verapamil: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of verapamil. Patients receiving both a CYP2D6 inhibitor plus verapamil may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; verapamil is a moderate CYP3A inhibitor.
Viloxazine: (Major) Recommendations for managing aripiprazole and viloxazine vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer a quarter of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 200 mg/month or from 300 mg to 160 mg/month. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; viloxazine is a weak CYP2D6 and weak CYP3A inhibitor.
Voclosporin: (Moderate) Concomitant use of aripiprazole and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Vonoprazan; Amoxicillin: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of vonoprazan. Patients receiving both a CYP2D6 inhibitor plus vonoprazan may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; vonoprazan is a weak CYP3A inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Concomitant use of aripiprazole and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, clarithromycin is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Major) Concomitant use of aripiprazole and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, clarithromycin is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of vonoprazan. Patients receiving both a CYP2D6 inhibitor plus vonoprazan may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; vonoprazan is a weak CYP3A inhibitor.
Voriconazole: (Contraindicated) Avoid concomitant use of aripiprazole and voriconazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use also increases aripiprazole exposure and risk for side effects. If concomitant use is necessary, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, voriconazole is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Contraindicated) Avoid concomitant use of aripiprazole and voriconazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use also increases aripiprazole exposure and risk for side effects. If concomitant use is necessary, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate, voriconazole is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation.
Vorinostat: (Major) Concomitant use of vorinostat and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Voxelotor: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of voxelotor. Patients receiving both a CYP2D6 inhibitor plus voxelotor may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; voxelotor is a moderate CYP3A inhibitor.
Zafirlukast: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of zafirlukast. Patients receiving both a CYP2D6 inhibitor plus zafirlukast may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; zafirlukast is a weak CYP3A inhibitor.
Zaleplon: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and zaleplon due to the risk for additive CNS depression and next-day psychomotor impairment; dose adjustments may be necessary.
Ziprasidone: (Major) Concomitant use of ziprasidone and aripiprazole should be avoided due to the potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. In addition, coadministration of atypical antipsychotics may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures.
Zolpidem: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and zolpidem due to the risk for additive CNS depression and next-day psychomotor impairment; dose adjustments may be necessary. Limit the dose of Intermezzo sublingual tablets to 1.75 mg/day.
Zonisamide: (Moderate) Zonisamide may cause decreased sweating (oligohidrosis), elevated body temperature (hyperthermia), heat intolerance, or heat stroke. The manufacturer recommends caution in using concurrent drug therapies that may predispose patients to heat-related disorders such as antipsychotics. Monitor patients for heat intolerance, decreased sweating, or increased body temperature if zonisamide is used with any of these agents.

Abilify Asimtufii/Aristada Intramuscular Inj Susp ER: 1.6mL, 2.4mL, 3.2mL, 3.9mL, 441mg, 662mg, 675mg, 720mg, 882mg, 960mg, 1064mg
Abilify Discmelt/Aripiprazole Oral Tab Orally Dis: 10mg, 15mg
Abilify Maintena Intramuscular Inj Pwd F/Susp ER: 300mg, 400mg
Abilify/Abilify Mycite/Aripiprazole Oral Tab: 2mg, 5mg, 10mg, 15mg, 20mg, 30mg
Abilify/Aripiprazole Oral Sol: 1mg, 1mL

Adults

30 mg/day PO tablets and 25 mg/day PO oral solution; 30 mg/day immediate-release IM; 400 mg/month extended-release IM (Abilify Maintena); 960 mg every 2 months extended-release IM (Abilify Asimtufii); 882 mg/month extended-release IM (Aristada); 675 mg IM single-dose administration (Aristada Initio).

Geriatric

30 mg/day PO tablets and 25 mg/day PO oral solution; 30 mg/day immediate-release IM; 400 mg/month extended-release IM (Abilify Maintena); 960 mg every 2 months extended-release IM (Abilify Asimtufii); 882 mg/month extended-release IM (Aristada); 675 mg IM single-dose administration (Aristada Initio), but safety and efficacy of Aristada and Aristada Initio have not established in geriatric adults older than 65 years of age.

Adolescents

Weighing 50 kg or more: 30 mg/day PO for schizophrenia and bipolar disorder; 15 mg/day PO for autism; 20 mg/day PO for Tourette's syndrome; safety and efficacy of the immediate-release (Abilify) and extended-release IM injections (Abilify Maintena, Abilify Asimtufii, Aristada, Aristada Initio) have not been established.
Weighing less than 50 kg: 30 mg/day PO for schizophrenia and bipolar disorder; 15 mg/day PO for autism; 10 mg/day PO for Tourette's syndrome; safety and efficacy of the immediate-release (Abilify) and extended-release IM injections (Abilify Maintena, Abilify Asimtufii, Aristada, Aristada Initio) have not been established.

Children

10 to 12 years and weighing 50 kg or more: 30 mg/day PO for bipolar disorder; 15 mg/day PO for autism; 20 mg/day PO for Tourette's syndrome; not indicated for schizophrenia.
10 to 12 years and weighing less than 50 kg: 30 mg/day PO for bipolar disorder; 15 mg/day PO for autism; 10 mg/day PO for Tourette's syndrome; not indicated for schizophrenia.
6 to 9 years and weighing 50 kg or more: 15 mg/day PO for autism; 20 mg/day PO for Tourette's syndrome; not indicated for bipolar disorder or schizophrenia.
6 to 9 years weighing less than 50 kg: 15 mg/day PO for autism; 10 mg/day PO for Tourette's syndrome; not indicated for bipolar disorder or schizophrenia.
Less than 6 years: Safety and efficacy have not been established.

Infants

Not indicated.

Neonates

Not indicated.

The mechanism of action of aripiprazole is fundamentally different from most currently available antipsychotics. While active at both dopamine and serotonin receptors like other antipsychotics, aripiprazole is a partial agonist at the dopaminergic D2 receptor and at the serotonergic 5-HT1A receptor and is an antagonist at the serotonergic 5-HT2A receptor. The partial agonist activity at the D2 receptor is a result of the drug acting as an antagonist at postsynaptic D2 receptors and a weak agonist at presynaptic D2 receptors. There appears to be activation at the receptor in states of low dopaminergic tone and inhibition at the receptor in states of high dopaminergic tone. Aripiprazole does have a high affinity for the D2 receptor, although the activity is less than that of haloperidol or chlorpromazine. The actions at the D2, 5-HT1A and 5-HT2A receptors are thought to mediate antipsychotic action of aripiprazole, as data indicate that the dopamine and serotonin systems are important in the pathology of the symptoms of schizophrenia. Aripiprazole has a higher affinity for 5-HT1A and 5-HT2A receptors relative to the D2 receptor, which may explain the drug's lower propensity to cause extrapyramidal side effects. Actions at receptors other than D2, 5-HT1A, and 5-HT2A include activities at the D3, D4, 5-HT2C, 5-HT7, alpha-1 adrenergic and histamine receptors (H1 receptors), which may explain some of the clinical effects of aripiprazole such as orthostatic hypotension and somnolence. Aripiprazole lauroxil is a pro-drug of aripiprazole; the activity of this pro-drug is primarily due to aripiprazole, and to a lesser extent dehydroaripiprazole.

Aripiprazole is administered orally or intramuscularly. The extended-release intramuscular formulations of aripiprazole lauroxil (Aristada and Aristada Initio) are pro-drugs of aripiprazole; following intramuscular administration, aripiprazole lauroxil is likely converted through enzyme-mediated hydrolysis to N-hydroxymethylaripiprazole, and then by water-mediated hydrolysis to aripiprazole. At therapeutic concentrations, aripiprazole and its major metabolite are more than 99% bound to serum proteins, primarily albumin. There appears to be dose-dependent D2-receptor occupancy, indicating brain penetration in humans. It is metabolized primarily by 3 pathways: dehydrogenation, hydroxylation, and N-dealkylation. The isoenzymes CYP3A4 and CYP2D6 are responsible for dehydrogenation and hydroxylation, and N-dealkylation is catalyzed by CYP3A4. At steady state, the active metabolite dehydroaripiprazole represents about 40% of the aripiprazole AUC in plasma. Approximately 25% of an administered dose is excreted in the urine as metabolites, less than 1% as unchanged drug. Fifty-five percent is excreted in the feces as metabolites with 18% as unchanged drug. The mean elimination half-lives of aripiprazole and dehydroaripiprazole are about 75 hours and 94 hours, respectively, with use of immediate-release dosage forms. The mean elimination half-life of extended-release intramuscular aripiprazole (i.e., Abilify Maintena) after multiple 4-week injections of the 300 mg and 400 mg dose is 29.9 days and 46.5 days, respectively. The mean elimination half-life of the extended-release intramuscular injection Aristada ranges from 53.9 to 57.2 days after monthly, 6-week, and 2-month injections. The mean elimination half-life of Aristada Initio is 15 to 18 days post-injection. The significantly longer half-lives of the various extended-release intramuscular injections are due to the dissolution and rate-limited elimination attributes of these formulations.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CYP2D6
Metabolism of aripiprazole occurs mainly through CYP3A4 and CYP2D6. Dosage adjustments are required in patients taking certain CYP2D6 or CYP3A4 inhibitors or combinations of CYP2D6 and 3A4 inhibitors, especially for a prolonged period of time, recommendations for adjustments vary depending on the dosage form prescribed. Review drug interactions. Avoid use of the Aristada Initio product in patients receiving strong CYP3A4 or CYP2D6 inhibitors or strong CYP3A4 inducers because the dose cannot be modified. Aripiprazole does not inhibit or induce CYP isoenzymes CYP2D6, CYP2C9, CYP2C19, or CYP3A4.

Oral Route

Oral aripiprazole is well absorbed with 87% absolute bioavailability. Absorption following an oral dose is not affected by food. At equivalent doses, the plasma concentrations of aripiprazole from the solution are higher than that from the tablet formulation. In a relative bioavailability study comparing 30 mg aripiprazole as the oral solution to 30 mg aripiprazole tablets, the solution to tablet ratios of geometric mean Cmax and AUC values were 122% and 114%, respectively. The single-dose pharmacokinetics of aripiprazole were linear and dose-proportional at doses of 5 to 30 mg. Peak plasma concentrations occur within 3 to 5 hours following oral administration. Steady-state concentrations are attained within 14 days of oral dosing for both aripiprazole and its active metabolite dehydroaripiprazole. The mean Cmax following an immediate-release intramuscular dose is on average 19% higher than for oral tablets. The AUC within the first 2 hours is 90% higher for an immediate-release intramuscular dose versus an oral dose; although the systemic exposure is similar between the formulations over 24 hours. The mean elimination half-lives of aripiprazole and dehydroaripiprazole are about 75 hours and 94 hours, respectively with oral dosing.

Intramuscular Route

Abilify immediate-release (aripiprazole) intramuscular injection solution: The intramuscular injection solution of aripiprazole has an absolute bioavailability of 100%. Peak plasma concentrations occur within 1 to 3 hours following intramuscular administration. The mean Cmax following an intramuscular dose is on average 19% higher than for oral tablets. The AUC within the first 2 hours is 90% higher for an intramuscular dose versus an oral dose; although the systemic exposure is similar between the formulations over 24 hours. Pharmacokinetic data on the metabolism and elimination of intramuscular aripiprazole is not available, but is expected to be similar to the oral formulation of the drug.
Abilify Maintena (aripiprazole) extended-release monthly intramuscular injection suspension: Systemic absorption of the extended-release injection suspension is slow and prolonged due to low solubility of aripiprazole particles. Maximum plasma concentrations are attained at a median of 5 to 7 days. The mean elimination half-lives of the 300 mg and 400 mg dose administered every 4 weeks are 29.9 days and 46.5 days, respectively. Steady-state is attained by the fourth dose.
Abilify Asimtufii (aripiprazole) extended-release every 2 months intramuscular injection suspension: Plasma exposures at steady-state were compared to Abilify Maintena and found to be similar. Steady-state aripiprazole was attained by the fourth dose. The average plasma concentrations (Cavg) of aripiprazole were 263 ng/mL and 280 ng/mL for Abilify Asimtufii and Abilify Maintena, respectively. The Cmax of aripiprazole were 342 ng/mL and 344 ng/mL for Abilify Asimtufii and Abilify Maintena, respectively.
Aristada (aripiprazole lauroxil) extended-release intramuscular injection suspension: Aristada (aripiprazole lauroxil) is a pro-drug of aripiprazole. Following intramuscular (IM) administration, the drug is likely converted through enzyme-mediated hydrolysis to N-hydroxymethylaripiprazole, and then by water-mediated hydrolysis to aripiprazole. After a single intramuscular injection, aripiprazole appears in the systemic circulation in 5 to 6 days and continues to be released for an additional 36 days. The aripiprazole concentration increases with consecutive doses and reaches steady-state following the fourth monthly injection. With administration of oral aripiprazole for 21 days along with the first dose of Aristada injection, aripiprazole concentrations reach therapeutic concentrations within 4 days. Aripiprazole exposure is similar for deltoid and gluteal intramuscular injections of 441 mg. However, doses of 662 mg, 882 mg, or 1,064 mg require a gluteal injection. Administration of 882 mg IM every 6 weeks or 1,064 mg IM every 2 months results in plasma aripiprazole concentrations that are within the established therapeutic range for 441 mg and 882 mg IM monthly. The doses of 441 mg monthly and 882 monthly showed a similar clinical response to each other. The mean aripiprazole terminal elimination half-life ranged from 53.9 days to 57.2 days after monthly, 6-week, and 2 month injections of aripiprazole lauroxil. The difference in half-life between Aristada and oral aripiprazole is the result of the dissolution and formation rate-limited elimination of aripiprazole following Aristada administration.
Aristada Initio (aripiprazole lauroxil) single-dose extended-release intramuscular injection suspension: This dosage form exhibits different pharmacokinetic characteristics from the Aristada injection. Aristada Initio (aripiprazole lauroxil) is a pro-drug of aripiprazole. Following intramuscular (IM) administration, the drug is likely converted through enzyme-mediated hydrolysis to N-hydroxymethylaripiprazole, and then by water-mediated hydrolysis to aripiprazole. After a single intramuscular injection, aripiprazole appears in the systemic circulation on the day of the injection. The median time to reach peak plasma exposures is about 27 days (range: 16 to 35 days). When Aristada Initio is administered with a 30 mg oral dose of aripiprazole at the time of the first Aristada injection, relevant aripiprazole concentrations are attained within 4 days; the regimen negates the need to use oral aripiprazole dosing for 21 days along with the first Aristada injection. Aripiprazole exposure is similar between deltoid and gluteal intramuscular injections of Aristada Initio.

Pregnancy

Aripiprazole is present in human breast milk; however, there are insufficient data to assess the amount in human milk, the effects on the breastfed infant, or the effects on milk production. Consider the benefits of breast-feeding, the risk of potential infant exposure, and the risk of an untreated or inadequately treated condition. Milk to plasma ratios of approximately 0.18 to 0.2 have been estimated. However, there is a variation of about 11-fold in the relative infant dose (0.7% to 8.3%). Aripiprazole can accumulate in an infant due to the long elimination half-life of the drug (approximately 75 hours) and the immature hepatic and renal functions of the developing infant, particular if preterm or newborn. Data related to the safety of antipsychotics during breast-feeding are limited. It may be prudent to continue an existing antipsychotic regimen if ongoing treatment is deemed necessary during breast-feeding, since there is considerable individual variation in antipsychotic response. Alternate medications for consideration include olanzapine or quetiapine. Regardless of the antipsychotic used, closely monitor the breastfed infant for excessive drowsiness, lethargy, developmental delays, and other side effects. Combination treatment with antipsychotics may increase the risk of these adverse events.