Risperdal

Serotonin-Dopamine Antagonist (SDA) Antipsychotics

Hazardous Drugs Classification
NIOSH 2016 List: Group 2
NIOSH reviewed data from studies provided by the manufacturer and determined it is unlikely that drug poses a carcinogenic, reproductive, or developmental hazard to workers in a healthcare setting and is no longer considered a hazardous drug.

Oral Administration Oral Solid Formulations

Conventional Tablets: May be administered without regard to meals.
 
Orally-disintegrating tablets (ODT, e.g., Risperdal M-tab):
Do not open the blister or child-resistant pouch until ready to administer. Peel back foil to expose the tablet. Do not push the tablet through the foil because this could damage the tablet. Using dry hands, remove the tablet from the package unit.
Immediately place the entire tablet on the tongue. Allow the tablet to disintegrate in the mouth (will occur within seconds); the patient can then swallow the dissolved medicine with or without liquid. The patient should not split or chew the tablet.

Oral Liquid Formulations

Oral solution:
Can be administered directly from the calibrated oral dosing syringe, or can be mixed with a beverage prior to administration. The minimum volume accurately measured with the provided oral syringe is 0.25 mL and the maximum is 3 mL.
Compatible beverages for dilution include water, coffee, orange juice, and low-fat milk.
The solution is not compatible with cola or tea.

Injectable Administration

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

Intramuscular Administration

Reconstitution, Preparation, Administration, and Disposition Instructions for the Risperdal Consta Single-Use Dose Pack:
Refer to the "Instructions for Use" section of the product labeling for additional preparation and administration considerations and visual aids.
Only for deep intramuscular (IM) deltoid or gluteal injection; do not administer intravenously. Avoid inadvertent injection into a blood vessel. Alternate site with each injection. Alternate gluteal injections between buttocks and alternate arms between deltoid injections.
Do not substitute any components of the dose pack, including the Risperdal Consta vial, the pre-filled syringe with 2 mL of diluent for Risperdal Consta, the vial adapter, and the 2 Terumo SurGuard needles for IM injection.
To ensure correct dose delivery, administer full contents of the vial. Administer immediately after reconstitution.
Prior to admixing, remove dose pack from refrigerator and allow to come to room temperature for at least 30 minutes. Do not allow to warm any other way.
Remove cap from vial: Flip off colored cap from the vial without removing grey rubber stopper. Wipe top of grey stopper with an alcohol swab and allow to air dry.
Prepare vial adapter: Hold sterile blister; peel back and remove the paper backing. Do not remove vial adapter from blister. Do not touch the spike tip. This will result in contamination.
Connect vial adapter to vial: Place vial on a hard surface and hold by the base. Center the vial adapter over the grey rubber stopper and push straight down onto the vial top until it snaps securely into place. Do not place the vial adapter at an angle or diluent may leak upon transfer to vial.
Remove sterile blister: Remove vial adapter from sterile blister only when ready to remove the white cap from prefilled syringe. Keep vial vertical to prevent leaks. Hold base of vial and pull up on the sterile blister to remove. Do not shake. Do not touch exposed luer opening on vial adapter. This will result in contamination.
Use proper grip: Hold by white collar at the tip of the syringe. Do not hold syringe by the glass barrel during assembly.
Remove cap: Holding the white collar, snap off-white cap; do not twist or cut off. Do not touch syringe tip due to contamination. Discard broken off cap.
Connect syringe to vial adapter: Hold vial adapter by skirt to keep stationary. Hold syringe by white collar then insert tip into the luer opening of the vial adapter. Do not hold glass syringe barrel. This may cause white collar to loosen or detach. Attach syringe to vial adapter with a firm clockwise twisting motion until it feels snug. Do not over-tighten since this may cause the syringe tip to break.
Inject diluent: Inject entire amount of diluent from syringe into vial. Vial contents will now be under pressure. Keep holding down the plunger rod with thumb.
Suspend microspheres in diluent: While holding down the plunger rod, shake vigorously for at least 10 seconds. The suspension should appear uniform, thick and milky in color. Microspheres will be visible in the liquid. Immediately proceed to next step to keep suspension from settling.
Transfer suspension to syringe: Invert vial completely. Slowly pull plunger rod down to withdraw entire contents from the vial into syringe.
Remove vial adapter: Hold white collar on the syringe and unscrew from vial adapter. Tear section of vial label at the perforation and apply to syringe for ID. Discard both vial and vial adapter appropriately.
Select and attach needle: Use 1-inch needle for deltoid and 2-inch needle for gluteal administration. Peel blister pouch partially and use to grasp base of needle. Holding the white collar on the syringe, attach syringe to needle luer connection with a firm clockwise twisting motion until snug. Do not touch needle luer opening.
Just before injection - re-suspend injection suspension microspheres: Settling will occur after reconstitution. Fully remove blister pouch. Just before injection, shake syringe vigorously.
Remove transparent needle protector: Move needle safety device back towards the syringe. Then hold white collar on syringe and carefully pull the transparent needle protector straight off.
Remove air bubbles: Gently tap the syringe and slowly depress the plunger with the needle in an upright position.
Inject: Immediately inject (to avoid settling) entire contents of syringe in the upper outer quadrant of the gluteal area or the deltoid muscle of the arm.
Secure needle in safety device and discard: Using 1 hand, place needle safety device at a 45-degree angle on a hard, flat surface. Press down with a firm, quick motion until the needle is fully engaged in safety device. Check to confirm needle safety device is fully engaged. Discard in an approved sharps container along with unused needle in dose pack.
Avoid a needle stick injury: Do not use 2 hands. Do not intentionally disengage or mishandle the needle safety device. Do not straighten the needle or engage the safety device if the needle is bent or damaged.
Dispose of properly: Do not re-use dose pack components since this may affect device integrity or lead to performance deterioration.
 
Reconstitution, Preparation, Administration, and Disposition Instructions for the Rykindo Single-Use Dose Pack:
Refer to the "Instructions for Use" section of the product labeling for additional preparation and administration considerations and visual aids.
For gluteal intramuscular (IM) administration only. Do not inject by any other route. Alternate injections between the two buttocks.
Ensure all components of the kit are available, include a prefilled syringe, vial adapter, vial, and a needle with attached safety device.
Remove the dose pack from the refrigerator and allow package to sit at room temperature for at least 30 minutes before reconstituting. Do not warm any other way. Only prepare medication when ready to administer the dose.
Remove cap from vial: Flip off the colored cap from the vial and wipe the top of the gray stopper with an alcohol swab. Allow to air dry. Do not remove the gray rubber stopper.
Prepare vial adapter: Holding the sterile blister pack, peel back the paper backing and remove it, being careful not to touch the spike tip at any time. Touching will result in contamination. Do not remove the vial adapter from the blister.
Connect vial adapter to vial: Place the vial on a hard surface and hold by the base. Center the vial adapter over the gray rubber stopper. Push vial adapter straight down onto vial top until it snaps securely into place. Do not place the vial adapter on at an angle or diluent may leak during transfer to the vial.
Remove sterile blister: Remove vial adapter from sterile blister only when ready to remove the translucent gray cap from the prefilled syringe. Keep vial vertical to prevent leaks. Hold base of vial and pull up on the sterile blister to remove. Do not shake. Do not touch exposed luer opening on vial adapter. This will result in contamination.
Use proper grip: Hold by Luer-Lok adapter at the tip of the syringe. Do not hold syringe by the glass barrel during assembly.
Remove cap: Holding the transparent Luer-Lok adapter, unscrew the translucent gray cap; do not snap or cut off. Do not touch syringe tip due to contamination. Discard the unscrewed cap.
Connect syringe to vial adapter: Hold vial adapter by skirt to keep stationary. Hold syringe by Luer-Lok adapter then turn it to connect with the luer opening of the vial adapter. Do not hold glass syringe barrel. This may cause the Luer-Lok adapter to loosen or detach. Attach syringe to vial adapter with a firm clockwise twisting motion until it feels snug. Do not over-tighten since this may cause the syringe tip to break.
Inject diluent: Inject entire amount of diluent from syringe into vial. Vial contents will now be under pressure. Keep holding down the plunger rod with thumb.
Suspend microspheres in diluent: While holding down the plunger rod, shake vigorously for at least 30 seconds. The suspension should appear uniform, thick and milky in color. Immediately proceed to next step to keep suspension from settling.
Transfer suspension to syringe: Invert vial completely. Slowly pull plunger rod down to withdraw entire contents from the vial into syringe.
Remove vial adapter: Hold Luer-Lok adapter on the syringe and unscrew from vial adapter. Tear section of vial label at the perforation and apply to syringe for ID. Discard both vial and vial adapter appropriately.
Attach needle: Take out the needle for gluteal injection. Peel blister pouch partially and use to grasp base of needle. Holding the Luer-Lok adapter on the syringe, attach syringe to needle luer connection with a firm clockwise twisting motion until snug. Do not touch needle luer opening.
Just before injection - re-suspend powder: Fully remove blister pouch. Just before injection, shake syringe vigorously for 20 to 30 seconds until there is no deposition of powder, as some settling will have occurred.
Remove transparent needle protector: Move needle safety device back towards the syringe. Then hold the Luer-Lok adapter on syringe and carefully pull the transparent needle protector straight off. Do not twist the transparent needle protector, as the luer connection may loosen.
Remove air bubbles: Hold the syringe upright and gently tap the syringe to make any air bubbles rise to the top. Slowly and carefully press the plunger rod upward to remove air.
Inject: Immediately inject (to avoid settling) entire contents of syringe in the upper outer quadrant of the gluteal muscle.
Secure needle in safety device and discard: Using 1 hand, place needle safety device at a 45-degree angle on a hard, flat surface. Press down with a firm, quick motion until the needle is fully engaged in safety device. Check to confirm needle safety device is fully engaged. Discard in an approved sharps container.

Subcutaneous Administration

Reconstitution, Preparation, Administration, and Disposition Instructions for Perseris Single-Dose Kit:
Refer to the Health care Provider "Instructions for Use" of the product labeling for additional preparation and administration information and visual aids.
For subcutaneous injection into the abdomen or back of the upper arm only. Do not administer by any other route.
Each injection must be administered by a health care professional.
Do not substitute any components of the prepackaged single-dose kit, which includes 1 liquid syringe pre-filled with the delivery system, one powder syringe pre-filled with risperidone powder, and 1 sterile 18-gauge, 5/8-inch safety needle.
As a universal precaution, always wear gloves.
Neither a loading dose nor supplemental oral risperidone is recommended. A patient who misses a dose should receive the next dose as soon as possible.
Allow package to come to room temperature for at least 15 minutes prior to preparation. Prepare medication when you are ready to administer the dose.
Tap Powder Syringe: Hold syringe upright and tap the barrel of the syringe to dislodge any powder that became packed during shipping.
Uncap Liquid and Powder Syringes: Remove cap from liquid syringe, then remove cap from powder syringe. Holding both syringes in your non-dominant hand can help with this step.
Connect the Syringes: Place liquid syringe on top of the powder syringe to prevent powder spillage and connect the syringes by twisting about 3/4 turn. Do not over tighten.
Premixing the Product: Failure to fully mix the medication could result in the incorrect dosage.
Transfer contents of the liquid syringe into the powder syringe.
Gently push the powder syringe plunger until you feel resistance (to wet powder and avoid compacting).
Repeat this gentle back-and-forth process for 5 cycles.
Complete Mixing: Continue mixing syringes for an additional 55 cycles. This mixing can be more vigorous than when premixing.
When fully mixed, the suspension should be cloudy and uniform in color.
Color may vary from white to yellow-green.
If clear areas are seen in the mixture, mix until the color distribution is uniform.
Prepare Injection Syringe: Failure to aspirate the liquid from the powder syringe may result in an incorrect dosage.
First, transfer all contents into the liquid syringe.
Next, perform the following 2 actions SIMULTANEOUSLY: maintain slight pressure on the powder syringe plunger, AND pull back gently on the liquid syringe plunger while twisting the syringes apart.
Finally, attach the safety needle by twisting until finger tight.
Check that the medication is uniform in color and free from foreign particles.
Prepare the Injection Site: Choose an injection site on the abdomen or back of the upper arm with adequate subcutaneous tissue free of skin conditions. Do not inject into an area where the skin is irritated, reddened, bruised, infected, or scarred in any way.
Clean injection site well with an alcohol pad.
Rotate injection sites following a pattern similar to that shown in the product labeling to help minimize irritation. If you want to use the same injection site, make sure it is a different spot on the injection site than was used for the last injection.
Remove Excess Air from Syringe: Hold syringe upright for several seconds to allow air bubbles to rise.
Remove needle cover and slowly depress the plunger to push out excess air from syringe.
If medication is seen at needle tip, pull back slightly on the plunger to prevent medication spillage.
Bubbles will not rise as quickly as those in an aqueous solution due to suspension viscosity.
Pinch Injection Site: Pinch enough skin around injection area to accommodate needle size. Lift adipose tissue from underlying muscle to prevent IM injection.
Inject the Medication: Insert needle fully into the subcutaneous tissue. Inject medication slow and steady. Actual angle of injection will depend on the amount of subcutaneous tissue.
Withdraw Needle: Withdraw the needle at the same angle used for insertion and release pinched skin. Do not rub injection area after injection. If bleeding occurs, apply a gauze pad or bandage, but use minimal pressure.
Lock the Needle Guard and Dispose of Syringe: Lock the needle guard into place by pushing it against a hard surface. Dispose of all syringe components in a secure sharps disposal container.
Instruct the Patient: Advise the patient that they may have a lump for several weeks that will decrease in size over time. It is important that the patient not rub or massage the injection site and to be aware of the placement of any belts, waistbands, sleeves, cuffs, or other parts of clothing around the injected site.
 
Preparation, Administration, and Disposition Instructions for Uzedy Single-Dose Kit:
Refer to the Health care Provider "Instructions for Use" of the product labeling for additional preparation and administration information and visual aids.
For subcutaneous injection into the abdomen or back of the upper arm only. Do not administer by any other route.
Each injection must be administered by a health care professional. Follow universal precautions.
Make sure the Uzedy kit contains one sterile single-dose, prefilled glass syringe and a sterile 21 gauge, 5/8 inch safety needle. Do not substitute any components of the kit for administration.
Remove the kit from refrigerated storage and allow the package to sit at room temperature (20 to 25 degrees C; 68 to 77 degrees F) for at least 30 minutes.
Uzedy is a solid at refrigerated temperatures and must reach room temperature prior to administration. Do not warm any other way and keep protected from light.
Check that the medication in the syringe is white to off-white, opaque, and free from non-white particulate matter. Check that the pouch label states the needle size is 21 gauge and 5/8 inch.
Do not use if any component of the kit is damaged or if the expiration date has passed.
Expose the safety needle hub by peeling back the paper tab of the needle pouch. Set aside for use after mixing the syringe.
Firmly hold the syringe by the white collar. Flick syringe forcefully with a downward whipping motion of your full arm 3 times to move the bubble to the cap of the syringe. Standing while doing this may help achieve required force.
This step must be performed to ensure complete dosing. Uzedy is viscous and forceful downward flicks are required to move the bubble to the cap of the syringe. Failure to move the bubble to the cap of the syringe could result in incomplete dosage.
Check that the bubble is at the cap of the syringe.
The bubble will appear partially opaque; holding the syringe up to light or against a dark backdrop may improve visibility.
If the bubble is not at the cap, repeat steps above until it is.
Hold the syringe vertically by the white collar. Bend and snap off the cap. Do not touch the syringe tip to avoid contamination.
Hold the syringe vertically with the white collar at the top.
Push the green hub of the safety needle inside the white collar of the syringe and rotate the safety needle while holding the white collar until secure and tight. Inspect the needle connection to ensure that the hub is not damaged.
Select injection site from the following areas:
Stomach area (abdomen) around the belly button
Back and outer area of the upper arms
Do not inject Uzedy anywhere except in the areas specified above. Do not inject into an area that is tender, red, bruised, callused, tattooed, hard, or has scars or stretch marks.
Clean the injection site with an alcohol wipe.
Remove the needle sheath by pulling the needle sheath away from the green hub to expose the needle. Do not expel any visible air bubble.
Pinch at least 1 inch of the area of cleaned skin with your free hand.
Insert the needle into subcutaneous tissue (angle of injection will depend on the amount of subcutaneous tissue). Do not apply pressure to the plunger.
Release the pinched skin once the needle is in the subcutaneous tissue.
Push on the plunger using a slow, firm, and steady push until the entire dose is delivered. Inject the entire dose at one time, without interruption. Check that the plunger stopper is at the white collar.
NOTE: Uzedy is viscous, and resistance will be experienced during dose delivery. Do not use excessive force in an attempt to deliver Uzedy faster.
Wait 2 to 3 seconds after the entire dose is delivered before removing the needle. Slowly pull the needle out from the injection site at the same angle as insertion.
Activate (lock) the safety needle shield using one of the following methods:
Surface activation: Place the needle shield on a flat surface and pull the syringe backward until the needle shield covers the needle tip.
Finger/thumb activation: Press either your thumb or finger on the needle shield and push it forward until the needle shield covers the needle tip.
There will be an audible click when the needle safety shield is locked.
Dispose of all syringe components in a suitable sharps container.

Severe

tardive dyskinesia / Delayed / 0.1-5.3
seizures / Delayed / 0-0.3
suicidal ideation / Delayed / Incidence not known
akinesia / Delayed / Incidence not known
neuroleptic malignant syndrome / Delayed / Incidence not known
water intoxication / Delayed / Incidence not known
SIADH / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
cardiac arrest / Early / Incidence not known
bradycardia / Rapid / Incidence not known
AV block / Early / Incidence not known
atrial fibrillation / Early / Incidence not known
torsade de pointes / Rapid / Incidence not known
diabetic ketoacidosis / Delayed / Incidence not known
ileus / Delayed / Incidence not known
GI obstruction / Delayed / Incidence not known
rhabdomyolysis / Delayed / Incidence not known
ocular hypertension / Delayed / Incidence not known
visual impairment / Early / Incidence not known
retinal thrombosis / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
stroke / Early / Incidence not known
pulmonary embolism / Delayed / Incidence not known
tissue necrosis / Early / Incidence not known

Moderate

pseudoparkinsonism / Delayed / 0-28.0
constipation / Delayed / 5.0-17.0
hyperglycemia / Delayed / 0.8-12.6
akathisia / Delayed / 0-11.0
urinary incontinence / Early / 1.0-7.0
blurred vision / Early / 1.0-7.0
hypercholesterolemia / Delayed / 4.3-6.3
hyperlipidemia / Delayed / 2.5-6.3
dystonic reaction / Delayed / 0-6.0
sinus tachycardia / Rapid / 1.0-3.0
hypertension / Early / 0-3.0
cystitis / Delayed / 1.0-3.0
hypertriglyceridemia / Delayed / 2.5-2.7
orthostatic hypotension / Delayed / 0-2.0
chest pain (unspecified) / Early / 2.0-2.0
dyspnea / Early / 1.0-2.0
diabetes mellitus / Delayed / 0-0.4
hyperprolactinemia / Delayed / 10.0
confusion / Early / Incidence not known
mania / Early / Incidence not known
depression / Delayed / Incidence not known
dyskinesia / Delayed / Incidence not known
hyperthermia / Delayed / Incidence not known
hyponatremia / Delayed / Incidence not known
edema / Delayed / Incidence not known
peripheral edema / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
erythema / Early / Incidence not known
atopic dermatitis / Delayed / Incidence not known
bundle-branch block / Early / Incidence not known
hypotension / Rapid / Incidence not known
QT prolongation / Rapid / Incidence not known
hypoglycemia / Early / Incidence not known
glycosuria / Early / Incidence not known
gastritis / Delayed / Incidence not known
dysphagia / Delayed / Incidence not known
pneumonitis / Delayed / Incidence not known
fecal incontinence / Early / Incidence not known
infertility / Delayed / Incidence not known
precocious puberty / Delayed / Incidence not known
galactorrhea / Delayed / Incidence not known
dysuria / Early / Incidence not known
priapism / Early / Incidence not known
impotence (erectile dysfunction) / Delayed / Incidence not known
urinary retention / Early / Incidence not known
ejaculation dysfunction / Delayed / Incidence not known
myasthenia / Delayed / Incidence not known
blepharospasm / Early / Incidence not known
photophobia / Early / Incidence not known
conjunctival hyperemia / Early / Incidence not known
conjunctivitis / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
wheezing / Rapid / Incidence not known
ocular infection / Delayed / Incidence not known
skin ulcer / Delayed / Incidence not known
hematoma / Early / Incidence not known
withdrawal / Early / Incidence not known

Mild

appetite stimulation / Delayed / 1.7-44.0
weight gain / Delayed / 8.0-32.6
injection site reaction / Rapid / 5.0-21.0
vomiting / Early / 10.0-20.0
cough / Delayed / 2.0-17.0
anxiety / Delayed / 0-16.0
abdominal pain / Early / 13.0-16.0
nausea / Early / 3.0-16.0
fever / Early / 1.0-16.0
rhinorrhea / Early / 12.0-12.0
tremor / Early / 0-11.0
dyspepsia / Early / 3.0-10.0
hypersalivation / Early / 0-10.0
xerostomia / Early / 0-10.0
nasal congestion / Early / 4.0-10.0
rhinitis / Early / 9.0-9.0
rash / Early / 1.0-8.0
diarrhea / Early / 1.0-8.0
polydipsia / Early / 0-7.0
nocturia / Early / 7.0-7.0
back pain / Delayed / 1.0-6.8
anorexia / Delayed / 6.0-6.0
musculoskeletal pain / Early / 0-5.2
weight loss / Delayed / 1.0-4.0
amenorrhea / Delayed / 4.0-4.0
arthralgia / Delayed / 2.0-4.0
xerosis / Delayed / 0-3.0
dental pain / Delayed / 1.0-3.0
muscle cramps / Delayed / 0-2.6
acne vulgaris / Delayed / 2.0-2.0
syncope / Early / 1.0-2.0
sinusitis / Delayed / 1.0-2.0
agitation / Early / Incidence not known
hypothermia / Delayed / Incidence not known
malaise / Early / Incidence not known
chills / Rapid / Incidence not known
pruritus / Rapid / Incidence not known
maculopapular rash / Early / Incidence not known
hyperkeratosis / Delayed / Incidence not known
skin discoloration / Delayed / Incidence not known
photosensitivity / Delayed / Incidence not known
night sweats / Early / Incidence not known
alopecia / Delayed / Incidence not known
seborrhea / Delayed / Incidence not known
skin hyperpigmentation / Delayed / Incidence not known
polyuria / Early / Incidence not known
cheilitis / Delayed / Incidence not known
dysgeusia / Early / Incidence not known
breast discharge / Delayed / Incidence not known
vaginal discharge / Delayed / Incidence not known
menstrual irregularity / Delayed / Incidence not known
mastalgia / Delayed / Incidence not known
gynecomastia / Delayed / Incidence not known
breast enlargement / Delayed / Incidence not known
menorrhagia / Delayed / Incidence not known
oligomenorrhea / Delayed / Incidence not known
libido decrease / Delayed / Incidence not known
orgasm dysfunction / Delayed / Incidence not known
increased urinary frequency / Early / Incidence not known
myalgia / Early / Incidence not known
lacrimation / Early / Incidence not known
xerophthalmia / Early / Incidence not known
blepharedema / Early / Incidence not known
ocular discharge / Delayed / Incidence not known
otalgia / Early / Incidence not known
tinnitus / Delayed / Incidence not known
flushing / Rapid / Incidence not known
hyperventilation / Early / Incidence not known
pharyngitis / Delayed / Incidence not known
influenza / Delayed / Incidence not known
infection / Delayed / Incidence not known
skin irritation / Early / Incidence not known
ecchymosis / Delayed / Incidence not known

Dementia, geriatric, stroke

Antipsychotics are not approved for the treatment of dementia-related psychosis in geriatric adults and use of risperidone should be avoided if possible due to an increase in morbidity and mortality in elderly adults 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. Lower initial dosages of risperidone are generally recommended for the geriatric adult, with careful titration, to minimize risks for orthostasis and hypotension. Monitor blood pressure and renal function. 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 risperidone 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.

PERSERIS, Risperdal, Risperdal Consta, Risperdal M-Tab, Rykindo, UZEDY

Rx

Oral and parenteral atypical antipsychotic of the benzisoxazole class
Used orally and as an extended-release (ER) intramuscular injection in adults for schizophrenia and bipolar I disorder; a subcutaneous ER injection is used for schizophrenia in adults; in selected pediatric patients used orally for schizophrenia, bipolar I disorder, and irritability associated with autistic disorder
As with all antipsychotics, boxed warning for increased mortality risk in elderly patients with dementia-related psychosis

For the treatment of schizophrenia. Oral dosage Adults

Initiate at 2 mg/day PO given as a single dose or as 1 mg PO twice per day. Adjust at intervals of at least 24 hours and in increments of 1 to 2 mg/day as tolerated to the recommended target dose of 4 to 8 mg/day PO. Effective range: 4 to 16 mg/day PO. May administer total daily dose once daily or in 2 divided doses. During clinical trial evaluation, doses more than 6 mg/day PO were not more effective than lower doses, and were associated with more extrapyramidal symptoms and other adverse effects. In one study, the efficacy results for 8 mg/day were generally greater than for 4 mg/day. Patient response to antipsychotics is variable. Individualize dosage. Use the lowest effective dose. Max: 16 mg/day PO. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. A dose reduction should be considered if hypotension occurs. Maintenance treatment is typically recommended for those responding to initial treatment. Periodically re-assess the need for continued treatment. In one controlled trial, doses of 2 to 8 mg/day effectively delayed relapse in adults who had been clinically stable for at least 4 weeks and were then followed for 1 to 2 years. RE-INITIATION OF TREATMENT: The initial dose titration should be followed in patients who have previously discontinued the drug.

Geriatric Adults

Initiate with 0.5 mg PO twice per day followed by careful titration to minimize risks for orthostasis/syncope. Adjust at intervals of at least 24 hours and in increments of 1 to 2 mg/day as tolerated; geriatric adults may need slower titration. Target dosage range: 4 to 8 mg/day PO. Effective dose range: 4 to 16 mg/day PO. May give the total daily dose once daily or in 2 divided doses. During clinical trial evaluation, doses more than 6 mg/day were not more effective than lower doses, and were associated with more extrapyramidal symptoms and other adverse effects. Individualize dosage. Use the lowest effective dose. Max: 16 mg/day PO. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. A dose reduction should be considered if hypotension occurs. Maintenance treatment is typically recommended for those responding to initial treatment. Periodically re-assess the need for continued treatment. RE-INITIATION OF TREATMENT: The initial dose titration should be followed in patients who have previously discontinued the drug.

Adolescents

0.5 mg PO once daily initially; may give in divided doses to increase tolerability. Adjust at intervals of at least 24 hours and in increments of 0.5 to 1 mg/day as tolerated to the recommended target dose of 3 mg/day. Effective dosage range: 1 to 6 mg/day PO; however, doses above 3 mg/day do not appear to provide additional therapeutic benefits and may result in more adverse events. Max: 6 mg/day PO. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Responding patients generally continue treatment beyond the acute episode. Periodically reassess safety and efficacy during chronic use.

Children† 8 to 12 years

Dosage not established; not FDA-approved. Literature suggests 0.5 mg/day PO initially. May give in divided doses to increase tolerability. Follow with gradual titration based on response and tolerability. Max: 6 mg/day PO. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In one randomized, controlled trial of pediatric patients with early-onset schizophrenia, schizoaffective disorder, or schizophreniform disorder, children 8 to 11 years received 0.5 mg/day PO on Day 1, with an increase to 1 mg/day on Day 6, 1.5 mg/day on Day 11, and 2 mg/day on Day 15 as clinically indicated; thereafter, gradual titration occurred as needed in increments of 1 mg/day, up to 6 mg/day PO. Children 12 years received 0.5 mg/day on Day 1, with titration up to 3 mg/day by Day 11, and titration thereafter as clinically indicated in increments of 1 mg/day, up to 6 mg/day PO.

Intramuscular depot dosage (i.e., Risperdal Consta, Rykindo)

NOTE: Establish tolerability with oral risperidone prior to starting IM therapy.

Adults

Usual dose: 25 mg deep IM once every 2 weeks. Risperdal Consta is given as a deep gluteal or deltoid injection; Rykindo is for deep gluteal injection only. Supplement with oral risperidone for 3 weeks after first injection of Risperdal Consta to maintain adequate plasma concentrations during initiation; Rykindo use requires a 7-day overlap with oral risperidone. Doses above 25 mg IM every 2 weeks do not appear to provide greater efficacy; however, some patients may benefit from 37.5 mg or 50 mg IM once every 2 weeks. Titrate at intervals of at least 4 weeks; response following titration should not be expected earlier than 3 weeks. Max: 50 mg IM once every 2 weeks. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Subcutaneous depot once-monthly dosage (Perseris only)

NOTE: Establish tolerability with oral risperidone before starting subcutaneous therapy.

Adults

90 mg or 120 mg subcutaneously once monthly. Max: 120 mg/month. Perseris may be given 1 day after the last oral risperidone dose; overlap of dosing is not required or recommended. SWITCHING FROM ORAL RISPERIDONE: Perseris 90 mg once monthly corresponds to 3 mg/day PO; Perseris 120 mg once monthly corresponds to 4 mg/day PO. Those taking oral risperidone less than 3 mg/day or more than 4 mg/day may not be candidates for Perseris. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. MISSED DOSE: Administer as soon as possible.

Subcutaneous depot once-monthly or every 2-month dosage (Uzedy only)

NOTE: Establish tolerability with oral risperidone before starting subcutaneous therapy.

Adults

Initiate the day after the last dose of oral therapy with a once monthly or every 2-month subcutaneous injection corresponding to the amount of oral risperidone taken daily. Overlap of dosing is not required or recommended. CONVERSION FROM ORAL RISPERIDONE: 2 mg/day PO corresponds to Uzedy 50 mg subcutaneously once monthly or 100 mg every 2 months; 3 mg/day PO corresponds to Uzedy 75 mg/month or 150 mg every 2 months; 4 mg/day PO corresponds to Uzedy 100 mg/month or 200 mg every 2 months; 5 mg/day PO corresponds to 125 mg/month or 250 mg every 2 months. Max: 125 mg once monthly or 250 mg every 2 months. SWITCHING FREQUENCY OF ADMINISTRATION: May switch between monthly and every 2-month doses by administering the first dose of the new regimen on the next scheduled date when an injection is due. MISSED DOSES: If a dose is missed, administer as soon as possible.

For the treatment of bipolar disorder. For the treatment of acute mania or mixed episodes associated with bipolar I disorder. Oral dosage Adults

2 to 3 mg PO once daily, initially, as monotherapy or adjunct therapy with lithium or valproate. Adjust dose by 1 mg/day every 24 hours or more based on clinical response and tolerability. Usual dose: 1 to 6 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Risperidone is FDA-approved in this population as monotherapy or as adjunct therapy with lithium and valproate.

Older Adults

0.5 mg PO once daily, initially. Adjust dose by 1 mg/day every 24 hours or more based on clinical response and tolerability. Usual dose: 1 to 6 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

0.5 mg PO once daily, initially. Adjust dose by 0.5 to 1 mg/day every 24 hours or more based on clinical response and tolerability. Children experiencing persistent somnolence may benefit from administering half the daily dose twice daily. Usual dose: 1 to 2.5 mg/day. Max: 6 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Risperidone is FDA-approved in this population as monotherapy.

For the maintenance treatment of bipolar I disorder as monotherapy or adjunct therapy to lithium or valproate. Intramuscular depot dosage (i.e., Risperdal Consta, Rykindo)

NOTE: Establish tolerability with oral risperidone prior to converting to IM therapy.

Adults

25 mg IM every 2 weeks. Supplement with oral risperidone after first injection for 3 weeks with Risperdal Consta and 1 week with Rykindo to maintain adequate plasma concentrations during initiation. Some persons may benefit from doses of 37.5 to 50 mg IM every 2 weeks. Adjust dose every 4 weeks or more based on clinical response and tolerability. Max: 50 mg IM every 2 weeks. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For the treatment of irritability associated with autistic disorder. Oral dosage Children and Adolescents 5 to 17 years and weighing 20 kg or more

0.5 mg PO once daily, initially, for at least 4 days. Then may increase to recommended dose of 1 mg PO daily. May administer in divided doses to increase tolerability. Maintain this dose for at least 14 days. Thereafter, adjust as clinically necessary at intervals of at least 2 weeks and increments of 0.5 mg/day PO. Effective dose range: 0.5 mg to 3 mg/day PO. Once sufficient clinical response has been achieved and maintained, consider gradually lowering the dose to achieve the optimal balance of safety and efficacy, and periodically re-assess during long-term treatment. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Children and Adolescents 5 to 17 years and weighing 15 to 19 kg

0.25 mg PO once daily, initially, for at least 4 days. Then may increase to recommended dose of 0.5 mg PO daily. May administer in divided doses to increase tolerability. Maintain this dose for at least 14 days. Thereafter, adjust as clinically necessary at intervals of at least 2 weeks and increments of 0.25 mg/day PO. Effective dose range: 0.5 mg to 3 mg/day PO. Once sufficient clinical response has been achieved and maintained, consider gradually lowering the dose to achieve the optimal balance of safety and efficacy, and periodically re-assess during long-term treatment. No dosing data are available for autistic disorder in pediatric patients weighing less than 15 kg. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For the treatment of moderate to severe tics associated with Tourette's syndrome† or chronic tic disorders†. Oral dosage Adults

A dosage range of 0.25 mg to 6 mg per day PO is recommended in evidence-based guidelines for the treatment of tic disorders. Initiate at the low end of the dosage range and titrate to response and tolerability. Results from small randomized studies suggest that the mean effective dose is approximately 2.5 to 4 mg/day. In one study, a mean risperidone dose of 3.8 mg/day (range: 0.5 mg/day to 6 mg/day) was similar in efficacy to a mean pimozide dose of 2.9 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. The American Academy of Neurology (AAN) practice guideline states that risperidone 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 risperidone relative to other antipsychotics used to treat tics.

Children and Adolescents 7 to 17 years

Low initial doses are suggested (e.g., 0.25 to 0.5 mg/day PO); the usual effective dose range is 1 to 4 mg/day. Results from small randomized studies suggest the mean effective dose is approximately 2.5 mg/day. A separate study that included adolescents 14 years and older used a maximum of 6 mg/day PO; a median dose of 2.5 mg/day (range 1 to 6 mg/day) was superior to placebo. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. The American Academy of Child and Adolescent Psychiatry (AACAP) recommends atypical antipsychotics as a treatment option for patients with moderate to severe tics and in patients with tics with other comorbidities suitable for treatment with an antipsychotic. The American Academy of Neurology (AAN) practice guideline states that risperidone 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 risperidone relative to other antipsychotics used to treat tics.

For the treatment of moderate to severe disruptive behaviors† (e.g., aggression) associated with oppositional defiant disorder† or other disruptive behavioral disorders†. Oral dosage Adolescents

In one study, body weight was used to determine dosage. Those weighing less than 50 kg received 0.25 mg/day PO initially; if weight 50 kg or more, 0.5 mg/day PO was given initially. Thereafter, the dose was increased gradually by 0.25 mg for patients less than 50 kg or 0.50 mg for those weighing 50 kg or more to a maximum daily dose of 0.75 mg/day PO for patients less than 50 kg or 1.5 mg/day PO for those 50 kg or more. The mean risperidone dosage was approximately 0.02 mg/kg/day.] Doses have varied among studies. In a comprehensive review, the mean risperidone dose ranged from 0.98 to 1.5 mg/day at study end for all studies evaluated. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Children 5 to 12 years

0.01 mg/kg/day PO for at least 2 days is a suggested initial weight-based dose. Then, may titrate to 0.02 mg/kg/day for 5 days, and subsequently adjust weekly as clinically indicated by 0.02 mg/kg/day. Max: 0.06 mg/kg/day PO. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In one study, body weight was used to determine dosage. Those weighing less than 50 kg received 0.25 mg/day PO initially; if weight was 50 kg or more, 0.5 mg/day PO was given initially. Thereafter, the dose was increased gradually by 0.25 mg for patients less than 50 kg or 0.5 mg for those weighing 50 kg or more to a maximum daily dose of 0.75 mg/day PO for patients less than 50 kg or 1.5 mg/day PO for those 50 kg or more. The mean risperidone dosage was approximately 0.02 mg/kg/day.] Doses have varied among studies, with mean risperidone doses ranging from 0.98 to 1.7 mg/day at the end of the studies. In a double-blind, placebo-controlled study of 110 children with a disruptive behavior disorder (DBD) and subaverage IQ, the decline in symptom ratings was 47.3% in the risperidone group vs. 20.9% in the placebo group. At study end, 25% of children in the placebo group were rated by the investigator as improved to some degree compared to 77% of children in the risperidone group. Some data have demonstrated sustained long-term improvement. In a 9-week randomized trial of 168 children (age: 6 to 12 years) with attention-deficit/hyperactivity disorder (ADHD) and a DBD (ODD or conduct disorder), the addition of risperidone to a psychostimulant and parent training showed significant improvements in measures of aggression and serious behavioral problems compared to those receiving stimulant and parent training only. Risperidone therapy (mean dose: 1.7 +/- 0.75 mg/day) was added at weeks 4 to 6 only if there was a need for improvement. For children weighing less than 25 kg, risperidone 0.5 to 2.5 mg/day was given; for children 25 kg or more, doses ranged from 0.5 to 3.5 mg/day. In a post-hoc analysis of children with ADHD and a DBD, risperidone-treated children had clinically and statistically significant reductions in disruptive behavior and hyperactivity subscale scores compared to placebo, regardless of concomitant stimulant use. However, further study is needed on the use of risperidone in the treatment of ADHD. Efficacy in children with ADHD alone or in long term settings has not been established, and the drug is not without adverse effects.

For the treatment of delirium† in the pediatric intensive care unit (PICU). Oral dosage Children and Adolescents

Limited data available, particularly in young children. Maintenance doses ranging from 0.2 to 2 mg/day PO have been reported as efficacious with no adverse events noted (n = 30; age range: 4 months to 17 years). One small case series (n = 11; age range: 4 months to 16 years) used a loading dose of 0.1 to 0.2 mg PO. Begin at the lower end of the dosing range for younger, smaller patients. A mode individual dose of 0.5 mg has been reported in a small case series of older children and adolescents (n = 6; age range: 5 to 15 years). Some experts have suggested 0.5 to 2.5 mg/day PO given in 2 to 4 divided doses for patients 5 to 16 years of age. Max dosing is based on weight: less than 20 kg = 1 mg/day; 20 to 45 kg = 2.5 mg/day; more than 45 kg = 3 mg/day. In a review of data from 110 seriously-ill patients with delirium who were treated with atypical antipsychotics, a limited number of the same or lower doses were used as needed to control persistent symptoms and a routine daily dose was established based on the total amount needed to gain control of symptoms. Of those receiving risperidone (n = 13; mean age: 8.6 years; range: 1 to 16 years), a mean starting dose of 0.6 mg/day (range: 0.25 to 1 mg/day), mean ending dose of 0.7 mg/day (range: 0.25 to 2 mg/day), mean maximum dose of 1 mg/day (range: 0.25 to 2 mg/day), and average dose of 1.3 mg/day (range: 0.375 to 4 mg/day) was used. Antipsychotic was discontinued as soon as possible; mean length of therapy was 17.5 days (range: 2 to 54 days). Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

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

0.25 mg PO once or twice daily is a common initial dose. Study results indicate that risperidone 1 mg/day to 2 mg/day PO, given in divided doses, is more efficacious than placebo in improving dementia-related behavioral symptoms, especially psychosis and aggression. Suggested Max: 2 mg/day PO. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. According to the Agency for Healthcare Research and Quality efficacy review, risperidone is efficacious for behavioral symptoms of dementia. Risperidone is the only atypical antipsychotic with moderate to high quality in strength of efficacy evidence in all 3 dementia categories reviewed: dementia-overall behavioral symptoms, dementia-psychosis symptoms, and dementia-agitation symptoms. According to the European Academy of Neurology (EAN) dementia treatment guidelines, risperidone may be considered as first-line treatment if an antipsychotic is necessary in dementia patients with agitation or aggressive behavior. 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. Additionally, patients with dementia with Lewy bodies are thought to experience increased sensitivity to antipsychotics. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of antipsychotics in long-term care facility residents with dementia-related behavioral symptoms. The OBRA maximum recommended dose for risperidone is 2 mg/day PO unless there is documentation of necessity for higher doses. Tapering attempts or documentation of medical necessity are required in residents of long-term care facilities according to OBRA guidelines.

†Indicates off-label use

Hepatic Impairment

Oral formulations: In adult patients with a Child Pugh score of 10 to 15, the recommended initial starting dose is 0.5 mg PO twice daily; titrate in increments of 0.5 mg or less. For doses more than 1.5 mg PO twice daily, titrate in weekly intervals. Specific guidelines for pediatric patients are not available.
 
Intramuscular depot injection (Risperdal Consta, Rykindo): Adult patients with hepatic impairment should be treated with titrated doses of oral risperidone prior to initiating treatment with IM depot risperidone. In adults, the recommended oral titration starting dose is 0.5 mg PO twice a day during week 1; increase to 1 mg PO twice a day or 2 mg PO once daily during week 2. If at least 2 mg/day PO is well tolerated, 25 mg IM every 2 weeks may be considered; higher dosages are not recommended. Continue oral risperidone for 3 weeks after the first depot injection of Risperdal Consta, then discontinue. Oral risperidone should be continued for 7 days after the first depot injection of Rykindo before discontinuing. A slower titration beginning with 12.5 mg IM may be more appropriate for some patients. Efficacy of the 12.5 mg dose has not been evaluated in clinical trials.
 
Subcutaneous depot injection once-monthly (Perseris): Prior to initiating treatment, it is advisable that adult patients with hepatic impairment be carefully titrated up to at least 3 mg/day PO risperidone. If the 3 mg/day dose is tolerable and efficacious, a dose of 90 mg subcutaneously once monthly may be considered. The subcutaneous depot injection has not been studied in patients with hepatic impairment.
 
Subcutaneous depot injection once-monthly or every 2 months (Uzedy): Prior to initiating treatment, it is advisable that adult patients with hepatic impairment be carefully titrated up to at least 2 mg/day PO risperidone. If the 2 mg/day dose is tolerable and efficacious, a dose of 50 mg subcutaneously once monthly may be considered. The subcutaneous depot injection has not been studied in patients with hepatic impairment.

Renal Impairment

Oral formulations: In adult patients with a CrCl less than 30 mL/minute, the recommended initial starting dose is 0.5 mg PO twice daily; titrate in increments of 0.5 mg or less. For doses more than 1.5 mg PO twice daily, titrate in weekly intervals. Specific guidelines for pediatric patients are not available.
 
Intramuscular depot injection (Risperdal Consta, Rykindo): Adult patients with renal impairment should be treated with titrated doses of oral risperidone prior to initiating treatment with IM depot risperidone. In adults, the recommended oral titration starting dose is 0.5 mg PO twice a day during week 1; increase to 1 mg PO twice a day or 2 mg PO once daily during week 2. If at least 2 mg/day PO is well tolerated, 25 mg IM every 2 weeks of the depot injection may be considered. Continue oral risperidone for 3 weeks after the first depot injection of Risperdal Consta, then discontinue. Oral risperidone should be continued for 7 days after the first depot injection of Rykindo before discontinuing. A slower titration beginning with 12.5 mg IM may be more appropriate for some patients. Efficacy of the 12.5 mg dose has not been evaluated in clinical trials.
 
Subcutaneous depot injection once-monthly (Perseris): Prior to initiating treatment, it is advisable that adult patients with renal impairment be carefully titrated up to at least 3 mg/day PO risperidone. If the 3 mg/day dose is tolerable and efficacious, a dose of 90 mg subcutaneously once monthly may be considered. The subcutaneous depot injection has not been studied in patients with renal impairment.
 
Subcutaneous depot injection once-monthly or every 2 months (Uzedy): Prior to initiating treatment, it is advisable that adult patients with hepatic impairment be carefully titrated up to at least 2 mg/day PO risperidone. If the 2 mg/day dose is tolerable and efficacious, a dose of 50 mg subcutaneously once monthly may be considered. The subcutaneous depot injection has not been studied in patients with hepatic impairment.

Abarelix: (Major) Since abarelix can cause QT prolongation, abarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation including risperidone. Prescribers need to weigh the potential benefits and risks of abarelix use in patients that are taking drugs that can cause QT prolongation.
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: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of acebutolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving acebutolol concomitantly.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as diphenhydramine. This combination is commonly used in clinical practice; however, additive drowsiness or other CNS effects may occur. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of dihydrocodeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of dihydrocodeine 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of dihydrocodeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Acetaminophen; Chlorpheniramine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
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) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as diphenhydramine. This combination is commonly used in clinical practice; however, additive drowsiness or other CNS effects may occur. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
Acetaminophen; Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as risperidone, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking risperidone, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider using a lower risperidone dose. Monitor patients for sedation and respiratory depression.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone 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 risperidone, caution should be used when risperidone 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 adagrasib and risperidone 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.
Aldesleukin, IL-2: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psyhcotropic activity. Use with caution.
Alfentanil: (Moderate) Due to the sedative effects of risperidone, caution should be used when risperidone is given in combination with other centrally-acting medications including opiate agonists such as alfentanil.
Alfuzosin: (Moderate) Use risperidone and alfuzosin together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Alfuzosin may prolong the QT interval in a dose-dependent manner.
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) 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 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) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
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.
Amiodarone: (Major) Concomitant use of risperidone 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. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation.
Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with risperidone. Amisulpride causes dose- and concentration- dependent QT prolongation. Risperidone has been associated with a possible risk for QT prolongation and/or TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Amitriptyline: (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Amlodipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Amlodipine; Atorvastatin: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Amlodipine; Benazepril: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Amlodipine; Celecoxib: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Amlodipine; Olmesartan: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Amlodipine; Valsartan: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Amobarbital: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and barbiturates and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Additionally, monitor for unusual drowsiness and sedation during coadministration due to the risk for additive CNS depression. Concomitant use may decrease risperidone exposure and increase the risk for CNS depression. Risperidone is a CYP3A substrate, and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Amoxapine: (Moderate) Use caution during co-administration of amoxapine and risperidone. 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) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with risperidone. If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. Clarithromycin is associated with an established risk for QT prolongation and TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include risperidone.
Angiotensin II receptor antagonists: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of angiotensin II receptor antagonists. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving angiotensin II receptor antagonists concomitantly.
Angiotensin-converting enzyme inhibitors: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Apalutamide: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and apalutamide and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Concomitant use may decrease risperidone exposure. Risperidone is a CYP3A substrate and apalutamide is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Apomorphine: (Moderate) Use risperidone and apomorphine together with caution due to a potential for additive QT prolongation and sedation. Also, risperidone and apomorphine may reduce 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. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. 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.
Aripiprazole: (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.
Arsenic Trioxide: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with risperidone include arsenic trioxide.
Artemether; Lumefantrine: (Major) Concomitant use of drugs with a possible risk of QT prolongation and torsade de pointes, including artemether; lumefantrine and risperidone, should be avoided if possible. Consider ECG monitoring if risperidone must be used with artemether; lumefantrine.
Articaine; Epinephrine: (Major) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of risperidone. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal'. The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of risperidone. The use of other agents for vascular support is recommended when needed.
Asenapine: (Major) Avoid coadministration of risperidone and asenapine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may also 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. Asenapine has also been associated with QT prolongation.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and barbiturates and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Additionally, monitor for unusual drowsiness and sedation during coadministration due to the risk for additive CNS depression. Concomitant use may decrease risperidone exposure and increase the risk for CNS depression. Risperidone is a CYP3A substrate, and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
Aspirin, ASA; Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as risperidone, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking risperidone, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider using a lower risperidone dose. Monitor patients for sedation and respiratory depression.
Atazanavir: (Major) Avoid coadministration of atazanavir and risperidone when possible. Caution should be used in patients receiving atazanavir concurrently with drugs metabolized via CYP3A4 and known to cause QT prolongation. Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of risperidone and an increased potential for QT prolongation or other adverse effects. Serious and/or life-threatening drug interactions could potentially occur between atazanavir and risperidone.
Atazanavir; Cobicistat: (Major) Avoid coadministration of atazanavir and risperidone when possible. Caution should be used in patients receiving atazanavir concurrently with drugs metabolized via CYP3A4 and known to cause QT prolongation. Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of risperidone and an increased potential for QT prolongation or other adverse effects. Serious and/or life-threatening drug interactions could potentially occur between atazanavir and risperidone. (Major) Coadministration of risperidone, a CYP2D6 substrate, and cobicistat, a potent CYP2D6 inhibitor, may increase plasma concentrations of risperidone. When oral risperidone is given with a potent CYP2D6 inhibitor, the dose of risperidone should not exceed 8 mg/day PO in adults. When initiating therapy, titrate risperidone slowly. Upon discontinuation of the CYP2D6 inhibitor, the risperidone dose should be re-evaluated and increased if necessary. For the long-acting risperidone injection, the current adult dosage should be closely monitored when a potent CYP2D6 inhibitor is initiated or discontinued. An adjustment of the dose may be required.
Atenolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of atenolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving atenolol concomitantly.
Atenolol; Chlorthalidone: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of atenolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving atenolol concomitantly.
Atomoxetine: (Moderate) Concomitant use of atomoxetine and risperidone 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 risperidone can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Azithromycin: (Major) Concomitant use of risperidone and azithromycin 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: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and barbiturates and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Additionally, monitor for unusual drowsiness and sedation during coadministration due to the risk for additive CNS depression. Concomitant use may decrease risperidone exposure and increase the risk for CNS depression. Risperidone is a CYP3A substrate, and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with risperidone. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. 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. Risperidone has also been associated with a possible risk for QT prolongation and/or TdP; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Belladonna; Opium: (Moderate) Additive CNS depression may occur if opiate agonists are used concomitantly with risperidone. The dose of one or both drugs should be reduced.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with risperidone may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with risperidone 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. If benzhydrocodone is initiated in a patient taking risperidone, reduce initial dosage and titrate to clinical response. If risperidone is initiated a patient taking an opioid agonist, use a lower initial dose of risperidone and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Benzodiazepines: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Betaxolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of betaxolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving betaxolol concomitantly.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and risperidone 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 risperidone 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: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of bisoprolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving bisoprolol concomitantly.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of bisoprolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving bisoprolol concomitantly.
Brexpiprazole: (Major) Caution is advisable during concurrent use of brexpiprazole with other antipsychotics such as risperidone. 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.
Brimonidine; Timolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of timolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving timolol concomitantly.
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 risperidone, caution should be used when risperidone 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 risperidone, caution should be used when risperidone 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 risperidone, caution should be used when risperidone 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 risperidone, caution should be used when risperidone 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 risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Bumetanide: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Bupivacaine; Epinephrine: (Major) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of risperidone. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal'. The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of risperidone. The use of other agents for vascular support is recommended when needed.
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 risperidone and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Risperidone has a possible risk for QT prolongation and TdP. 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 risperidone 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 risperidone and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Risperidone has a possible risk for QT prolongation and TdP. 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 risperidone 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: (Moderate) Monitor for an increase in risperidone-related adverse effects if concomitant use with bupropion is necessary and reduce risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, an anticipatory dosage decrease may be considered prior to initiation of bupropion. Concomitant use may increase risperidone exposure. Additionally, bupropion is associated with a dose-related increase in seizures; antipsychotics may increase this risk. Risperidone is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. Concomitant use with other strong CYP2D6 inhibitors increased risperidone overall exposure by 2.5- to 9-fold.
Bupropion; Naltrexone: (Moderate) Monitor for an increase in risperidone-related adverse effects if concomitant use with bupropion is necessary and reduce risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, an anticipatory dosage decrease may be considered prior to initiation of bupropion. Concomitant use may increase risperidone exposure. Additionally, bupropion is associated with a dose-related increase in seizures; antipsychotics may increase this risk. Risperidone is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. Concomitant use with other strong CYP2D6 inhibitors increased risperidone overall exposure by 2.5- to 9-fold.
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: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and barbiturates and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Additionally, monitor for unusual drowsiness and sedation during coadministration due to the risk for additive CNS depression. Concomitant use may decrease risperidone exposure and increase the risk for CNS depression. Risperidone is a CYP3A substrate, and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Butalbital; Acetaminophen: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and barbiturates and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Additionally, monitor for unusual drowsiness and sedation during coadministration due to the risk for additive CNS depression. Concomitant use may decrease risperidone exposure and increase the risk for CNS depression. Risperidone is a CYP3A substrate, and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Butalbital; Acetaminophen; Caffeine: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and barbiturates and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Additionally, monitor for unusual drowsiness and sedation during coadministration due to the risk for additive CNS depression. Concomitant use may decrease risperidone exposure and increase the risk for CNS depression. Risperidone is a CYP3A substrate, and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and barbiturates and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Additionally, monitor for unusual drowsiness and sedation during coadministration due to the risk for additive CNS depression. Concomitant use may decrease risperidone exposure and increase the risk for CNS depression. Risperidone is a CYP3A substrate, and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and barbiturates and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Additionally, monitor for unusual drowsiness and sedation during coadministration due to the risk for additive CNS depression. Concomitant use may decrease risperidone exposure and increase the risk for CNS depression. Risperidone is a CYP3A substrate, and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Butorphanol: (Moderate) Concomitant use of butorphanol with risperidone can potentiate the effects of butorphanol on respiratory depression, CNS depression (e.g., dizziness, impaired mental function), and sedation. Use together with caution. If a centrally acting medication needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Cabergoline: (Moderate) Cabergoline should not be coadministered with risperidone due to mutually antagonistic effects on dopaminergic function. The dopamine antagonist action of risperidone 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 risperidone.
Cabotegravir; Rilpivirine: (Moderate) Use risperidone and rilpivirine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Calcium-channel blockers: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
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 risperidone. Concurrent use may result in additive CNS depression.
Carbamazepine: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and carbamazepine and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Additionally, monitor for unusual drowsiness and sedation during coadministration due to the risk for additive CNS depression. Concomitant use may decrease risperidone exposure and increase the risk for CNS depression. Risperidone is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. Concomitant use reduced risperidone overall exposure by 50%.
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 risperidone, caution should be used when risperidone 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 risperidone. 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: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of carteolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving carteolol concomitantly.
Carvedilol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of carvedilol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving carvedilol concomitantly.
Celecoxib; Tramadol: (Major) Concurrent use of tramadol and risperidone should be avoided if possible due to a possible increased risk of seizures. Seizures have been reported in patients receiving monotherapy with tramadol or antipsychotics at recommended doses. In addition, due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally-acting medications such as tramadol.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and risperidone. Concurrent use may result in additive CNS depression.
Central-acting adrenergic agents: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Ceritinib: (Major) Avoid coadministration of ceritinib with risperidone if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Reports of QT prolongation and torsade de pointes (TdP) during risperidone therapy are also noted by the manufacturer, primarily in the overdose setting.
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.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Chlorcyclizine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Chlordiazepoxide: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Chlordiazepoxide; Amitriptyline: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics. (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Chlordiazepoxide; Clidinium: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Chloroquine: (Major) Avoid coadministration of chloroquine with risperidone 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. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Chlorpheniramine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Chlorpheniramine; Dextromethorphan:

> (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of dihydrocodeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of dihydrocodeine 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of dihydrocodeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone. (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Chlorpheniramine; Phenylephrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Chlorpheniramine; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Chlorpromazine: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with risperidone include chlorpromazine. 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. 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.
Ciprofloxacin: (Moderate) Concomitant use of ciprofloxacin and risperidone 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.
Cisapride: (Contraindicated) Risperidone has been associated with a possible risk for QT prolongation and torsade de pointes (TdP); however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Because of the potential for TdP, use of cisapride with risperidone is contraindicated.
Citalopram: (Major) Concomitant use of risperidone and citalopram 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.
Clarithromycin: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with risperidone. If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. Clarithromycin is associated with an established risk for QT prolongation and TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Clemastine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Clevidipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
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) Concomitant use of clofazimine and risperidone 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.
Clomipramine: (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Clonazepam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Clorazepate: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Clozapine: (Moderate) Because both clozapine and risperidone have a possible risk for QT prolongation and/or torsade de pointes (TdP), caution is advisable during concurrent use. Reports of QT prolongation and TdP during risperidone therapy are noted primarily in the overdosage setting. Treatment with clozapine has been associated with QT prolongation, TdP, cardiac arrest, and sudden death. If coadministration is required, the patient's underlying medical conditions and additional potential risk factors should be considered. Patients with known risk factors for cardiac disease or arrhythmia should be closely monitored. In addition, coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, or seizures. Chronic administration of clozapine and risperidone may decrease the clearance of risperidone.
Cobicistat: (Major) Coadministration of risperidone, a CYP2D6 substrate, and cobicistat, a potent CYP2D6 inhibitor, may increase plasma concentrations of risperidone. When oral risperidone is given with a potent CYP2D6 inhibitor, the dose of risperidone should not exceed 8 mg/day PO in adults. When initiating therapy, titrate risperidone slowly. Upon discontinuation of the CYP2D6 inhibitor, the risperidone dose should be re-evaluated and increased if necessary. For the long-acting risperidone injection, the current adult dosage should be closely monitored when a potent CYP2D6 inhibitor is initiated or discontinued. An adjustment of the dose may be required.
Cocaine: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsades de pointes and should be used cautiously in combination with other drugs that also prolong the QT interval, including local anesthetics.
Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) Use risperidone and promethazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also 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. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) Use risperidone and promethazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also 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. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
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.
Crizotinib: (Major) Avoid coadministration of crizotinib with risperidone due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Risperidone has also been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP), primarily in the overdose setting.
Cyclizine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Cyproheptadine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Dacomitinib: (Moderate) Monitor for an increase in risperidone-related adverse effects if concomitant use with dacomitinib is necessary and reduce risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, an anticipatory dosage decrease may be considered prior to initiation of dacomitinib. Concomitant use may increase risperidone exposure. Risperidone is a CYP2D6 substrate and dacomitinib is a strong CYP2D6 inhibitor. Concomitant use with other strong CYP2D6 inhibitors increased risperidone overall exposure by 2.5- to 9-fold.
Dantrolene: (Moderate) Simultaneous use of skeletal muscle relaxants and other CNS depressants, such as antipsychotics, can increase CNS depression.
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.
Darunavir: (Major) Decreased risperidone doses may be required when coadministered with darunavir/ritonavir. Darunavir/ritonavir is expected to decrease the hepatic metabolism of the risperidone, resulting in increased risperidone concentrations. If coadministration of these drugs is warranted, do so with caution and careful monitoring.
Darunavir; Cobicistat: (Major) Coadministration of risperidone, a CYP2D6 substrate, and cobicistat, a potent CYP2D6 inhibitor, may increase plasma concentrations of risperidone. When oral risperidone is given with a potent CYP2D6 inhibitor, the dose of risperidone should not exceed 8 mg/day PO in adults. When initiating therapy, titrate risperidone slowly. Upon discontinuation of the CYP2D6 inhibitor, the risperidone dose should be re-evaluated and increased if necessary. For the long-acting risperidone injection, the current adult dosage should be closely monitored when a potent CYP2D6 inhibitor is initiated or discontinued. An adjustment of the dose may be required. (Major) Decreased risperidone doses may be required when coadministered with darunavir/ritonavir. Darunavir/ritonavir is expected to decrease the hepatic metabolism of the risperidone, resulting in increased risperidone concentrations. If coadministration of these drugs is warranted, do so with caution and careful monitoring.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Coadministration of risperidone, a CYP2D6 substrate, and cobicistat, a potent CYP2D6 inhibitor, may increase plasma concentrations of risperidone. When oral risperidone is given with a potent CYP2D6 inhibitor, the dose of risperidone should not exceed 8 mg/day PO in adults. When initiating therapy, titrate risperidone slowly. Upon discontinuation of the CYP2D6 inhibitor, the risperidone dose should be re-evaluated and increased if necessary. For the long-acting risperidone injection, the current adult dosage should be closely monitored when a potent CYP2D6 inhibitor is initiated or discontinued. An adjustment of the dose may be required. (Major) Decreased risperidone doses may be required when coadministered with darunavir/ritonavir. Darunavir/ritonavir is expected to decrease the hepatic metabolism of the risperidone, resulting in increased risperidone concentrations. If coadministration of these drugs is warranted, do so with caution and careful monitoring.
Dasatinib: (Moderate) Use dasatinib with caution in combination with risperidone as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes. Reports of QT prolongation and torsade de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Degarelix: (Major) Avoid coadministration of degarelix with risperidone due to the risk of reduced efficacy of degarelix; QT prolongation may also occur. Risperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; degarelix is a GnRH analog. Additionally, risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP), primarily in the overdose setting. Androgen deprivation therapy (i.e., degarelix) may also prolong the QT/QTc interval.
Desipramine: (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Desvenlafaxine: (Major) Coadministration of risperidone, a CYP2D6 substrate, and desvenlafaxine, a CYP2D6 inhibitor, may increase plasma concentrations of risperidone. Clinical studies have shown desvenlafaxine does not have a clinically relevant effect on CYP2D6 metabolism at doses less than 100 mg/day; hence, per desvenlafaxine product labeling, CYP2D6 substrates can be dosed at the original level when desvenlafaxine doses are 100 mg or less or when desvenlafaxine is discontinued. For desvenlafaxine doses more than 400 mg, product labeling recommends to reduce the risperidone dose by one-half.
Deutetrabenazine: (Moderate) Use risperidone and deutetrabenazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. 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 excessive sedation and somnolence during coadministration of risperidone and deutetrabenazine. Concurrent use may result in additive CNS depression.
Dexchlorpheniramine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone 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 risperidone, caution should be used when risperidone 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 risperidone 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: (Moderate) Monitor for an increase in risperidone-related adverse effects if concomitant use with bupropion is necessary and reduce risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, an anticipatory dosage decrease may be considered prior to initiation of bupropion. Concomitant use may increase risperidone exposure. Additionally, bupropion is associated with a dose-related increase in seizures; antipsychotics may increase this risk. Risperidone is a CYP2D6 substrate and bupropion is a strong CYP2D6 inhibitor. Concomitant use with other strong CYP2D6 inhibitors increased risperidone overall exposure by 2.5- to 9-fold.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as diphenhydramine. This combination is commonly used in clinical practice; however, additive drowsiness or other CNS effects may occur. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Dextromethorphan; Quinidine: (Major) Concomitant use of risperidone and fixed-dose combination quinidine; dextromethorphan is contraindicated. Avoid concomitant use of risperidone and quinidine alone if possible; use increases the risk for QT/QTc prolongation and torsade de pointes (TdP) and is expected to increase risperidone exposure. 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 an increase in risperidone-related adverse effects and reduce risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, an anticipatory dosage decrease may be considered prior to initiation of quinidine. Risperidone is a CYP2D6 substrate, and quinidine is a strong CYP2D6 inhibitor. Concomitant use with other strong CYP2D6 inhibitors increased risperidone overall exposure by 2.5- to 9-fold.
Diazepam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
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) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Dimenhydrinate: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
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) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as diphenhydramine. This combination is commonly used in clinical practice; however, additive drowsiness or other CNS effects may occur. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Diphenhydramine; Ibuprofen: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as diphenhydramine. This combination is commonly used in clinical practice; however, additive drowsiness or other CNS effects may occur. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Diphenhydramine; Naproxen: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as diphenhydramine. This combination is commonly used in clinical practice; however, additive drowsiness or other CNS effects may occur. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Diphenhydramine; Phenylephrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as diphenhydramine. This combination is commonly used in clinical practice; however, additive drowsiness or other CNS effects may occur. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
Diphenoxylate; Atropine: (Moderate) Concurrent administration of diphenoxylate/difenoxin with risperidone can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Disopyramide: (Major) Risperidone should be used cautiously and with close monitoring with disopyramide. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically.
Dofetilide: (Major) Coadministration of dofetilide and risperidone is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Dolasetron: (Moderate) Administer dolasetron with caution in combination with risperidone. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Dolutegravir; Rilpivirine: (Moderate) Use risperidone and rilpivirine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Donepezil: (Moderate) Use donepezil with caution in combination with risperidone as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Donepezil; Memantine: (Moderate) Use donepezil with caution in combination with risperidone as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Dopamine: (Minor) The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of risperidone.
Dorzolamide; Timolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of timolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving timolol concomitantly.
Doxazosin: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Doxepin: (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Doxylamine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Doxylamine; Pyridoxine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
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) Concomitant use of dronedarone with risperidone is contraindicated due to the potential risk of QT prolongation and torsade de pointes (TdP). Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1,600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Risperidone has been associated with a possible risk of QT prolongation and/or TdP, primarily in the overdose setting. In addition, dronedarone is an inhibitor of CYP2D6. Risperidone is a substrate for CYP2D6. Concomitant use of dronedarone with risperidone may increase risperidone concentration and further increase the risk for adverse cardiac effects.
Droperidol: (Major) Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). Any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with droperidol include risperidone. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically.
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.
Efavirenz: (Major) Coadministration of efavirenz and risperidone may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. In addition, efavirenz may induce the CYP3A4 metabolism of risperidone, potentially reducing the efficacy of risperidone by decreasing its systemic exposure.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of efavirenz and risperidone may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. In addition, efavirenz may induce the CYP3A4 metabolism of risperidone, potentially reducing the efficacy of risperidone by decreasing its systemic exposure.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of efavirenz and risperidone may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. In addition, efavirenz may induce the CYP3A4 metabolism of risperidone, potentially reducing the efficacy of risperidone by decreasing its systemic exposure.
Elbasvir; Grazoprevir: (Moderate) Administering risperidone with elbasvir; grazoprevir may result in elevated risperidone plasma concentrations. Risperidone is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Eliglustat: (Moderate) Use risperidone and eliglustat together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Coadministration of risperidone, a CYP2D6 substrate, and cobicistat, a potent CYP2D6 inhibitor, may increase plasma concentrations of risperidone. When oral risperidone is given with a potent CYP2D6 inhibitor, the dose of risperidone should not exceed 8 mg/day PO in adults. When initiating therapy, titrate risperidone slowly. Upon discontinuation of the CYP2D6 inhibitor, the risperidone dose should be re-evaluated and increased if necessary. For the long-acting risperidone injection, the current adult dosage should be closely monitored when a potent CYP2D6 inhibitor is initiated or discontinued. An adjustment of the dose may be required.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of risperidone, a CYP2D6 substrate, and cobicistat, a potent CYP2D6 inhibitor, may increase plasma concentrations of risperidone. When oral risperidone is given with a potent CYP2D6 inhibitor, the dose of risperidone should not exceed 8 mg/day PO in adults. When initiating therapy, titrate risperidone slowly. Upon discontinuation of the CYP2D6 inhibitor, the risperidone dose should be re-evaluated and increased if necessary. For the long-acting risperidone injection, the current adult dosage should be closely monitored when a potent CYP2D6 inhibitor is initiated or discontinued. An adjustment of the dose may be required.
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) Use risperidone and rilpivirine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Use risperidone and rilpivirine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Encorafenib: (Major) Avoid coadministration of encorafenib and risperidone due to the potential for additive QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes. Reports of QT prolongation and torsade de pointes during risperidone therapy have been reported, primarily in the overdosage setting.
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) Avoid coadministration of entrectinib with risperidone due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Enzalutamide: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and enzalutamide and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Concomitant use may decrease risperidone exposure. Risperidone is a CYP3A substrate and enzalutamide is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Epinephrine: (Major) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of risperidone. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal'. The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of risperidone. The use of other agents for vascular support is recommended when needed.
Eplerenone: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Epoprostenol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Eribulin: (Moderate) Monitor ECG if risperidone is coadministered with eribulin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Eribulin has also been associated with QT prolongation.
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) Concomitant use of risperidone and erythromycin 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.
Escitalopram: (Moderate) Concomitant use of escitalopram and risperidone 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.
Esketamine: (Major) Closely monitor patients receiving esketamine and risperidone 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.
Esmolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of esmolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving esmolol concomitantly.
Estazolam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
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).
Ethacrynic Acid: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Ethotoin: (Major) Because antipsychotics such as risperidone can lower the seizure threshold, the effectiveness of ethotoin as an anticonvulsant may be reduced. In addition, inducers of CYP3A4, such as ethotoin, may decrease plasma concentrations of risperidone and its active metabolite. Therefore, the manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a 3A4 inducer. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting an inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials.
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.
Felodipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhan ce the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and risperidone. Concurrent use may result in additive CNS depression.
Fentanyl: (Moderate) Concomitant use of fentanyl with other central nervous system (CNS) depressants such as risperidone can potentiate the effects of fentanyl and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of fentanyl 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. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of fentanyl and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
Fingolimod: (Moderate) Monitor ECG continuously overnight in a medical facility after the first fingolimod dose if risperidone is coadministered due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
Flecainide: (Major) Concomitant use of risperidone 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: (Moderate) Concomitant use of fluconazole and risperidone 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.
Fluoxetine: (Moderate) Monitor for an increase in risperidone-related adverse effects if concomitant use with fluoxetine is necessary and reduce risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, an anticipatory dosage decrease may be considered prior to initiation of fluoxetine. Concomitant use may increase risperidone exposure. 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. Risperidone is a CYP2D6 substrate and fluoxetine is a strong CYP2D6 inhibitor. Concomitant use has been observed to increase risperidone overall exposure by 2.5- to 2.8-fold.
Fluphenazine: (Moderate) Use risperidone and fluphenazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also 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. Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Flurazepam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Fluvoxamine: (Moderate) Use risperidone and fluvoxamine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine.
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: (Major) Concomitant use of risperidone and fosamprenavir may result in altered risperidone plasma concentrations. Risperidone is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is an inducer of P-gp and a potent inhibitor and moderate inducer of CYP3A4.
Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as risperidone. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Risperidone has also been associated with a possible risk for QT prolongation and TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
Fosphenytoin: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and fosphenytoin and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Concomitant use may decrease risperidone exposure. Risperidone is a CYP3A substrate and fosphenytoin is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Fostemsavir: (Moderate) Use risperidone and fostemsavir together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Furosemide: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly. Furthermore, two of four placebo-controlled trials showed that elderly patients with dementia-related psychosis receiving the combination of risperidone and furosemide had a higher incidence of mortality than those receiving either agent alone. The mechanism for this adverse association is unknown. Caution should be exercised when the combined use of risperidone and furosemide is necessary in those with dementia-related psychosis.
Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and risperidone. Concomitant use of gabapentin with risperidone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive 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.
Gemifloxacin: (Moderate) Use risperidone and gemifloxacin together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and risperidone together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Gilteritinib: (Moderate) Use caution and closely monitor for additive QT prolongation if concurrent use of gilteritinib and risperidone is necessary. Gilteritinib has been associated with QT prolongation. QT prolongation and torsade de pointes (TdP) during risperidone therapy have primarily occurred in the overdosage setting.
Glasdegib: (Major) Avoid coadministration of glasdegib with risperidone due to the potential for additive QT prolongation. If coadministration cannot be avoided, consider the patient's underlying disease state(s) and additional potential risk factors. 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. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes. Reports of QT prolongation and torsade de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
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: (Major) Avoid coadministration of goserelin with risperidone due to the risk of reduced efficacy of goserelin; QT prolongation may also occur. Risperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; goserelin is a GnRH analog. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Androgen deprivation therapy (i.e., goserelin) may also prolong the QT/QTc interval.
Granisetron: (Moderate) Use risperidone and granisetron together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with risperidone. Halogenated anesthetics can prolong the QT interval. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors.
Haloperidol: (Major) Caution is advisable when coadministering medications that have a possible risk of QT prolongation and torsade de pointes (TdP), including risperidone and haloperidol. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation than with routine oral dosing. Coadministration of haloperidol with risperidone may also 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.
Histrelin: (Major) Avoid coadministration of histrelin with risperidone due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Risperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval.
Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
Hydromorphone: (Moderate) Concomitant use of hydromorphone with other central nervous system (CNS) depressants can potentiate the effects of hydromorphone and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include risperidone. Prior to concurrent use of hydromorphone 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. Consider the patient's use of alcohol or illicit drugs. If hydromorphone is used concurrently with a CNS depressant, a reduced dosage of hydromorphone and/or the CNS depressant is recommended; start with one-third to one-half of the estimated hydromorphone starting dose when using hydromorphone extended-release tablets. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
Hydroxychloroquine: (Major) Concomitant use of risperidone and hydroxychloroquine 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) Use risperidone and hydroxyzine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including risperidone. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
Ibuprofen; Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as risperidone, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking risperidone, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider using a lower risperidone dose. Monitor patients for sedation and respiratory depression.
Ibutilide: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval, such as risperidone. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically.
Iloperidone: (Major) Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as risperidone. 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. 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.
Imipramine: (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
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.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with risperidone 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. Risperidone has been associated with a possible risk for QT prolongation and/or TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
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.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and rifampin and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Concomitant use may decrease risperidone exposure. Risperidone is a CYP3A substrate and rifampin is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Isoniazid, INH; Rifampin: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and rifampin and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Concomitant use may decrease risperidone exposure. Risperidone is a CYP3A substrate and rifampin is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Isradipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Itraconazole: (Moderate) Use risperidone and itraconazole together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Itraconazole has also been associated with prolongation of the QT interval.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with risperidone 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. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes. Reports of QT prolongation and torsade de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and risperidone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Labetalol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of labetalol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving labetalol concomitantly.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with risperidone. If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. Clarithromycin is associated with an established risk for QT prolongation and TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Lapatinib: (Moderate) Monitor for evidence of QT prolongation if lapatinib is administered with risperidone. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and risperidone. Concurrent use may result in additive CNS depression.
Lefamulin: (Major) Avoid coadministration of lefamulin with risperidone as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
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.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with risperidone due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Risperidone has also been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP), primarily in the overdose setting.
Leuprolide: (Major) Avoid coadministration of leuprolide with risperidone due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Risperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Leuprolide; Norethindrone: (Major) Avoid coadministration of leuprolide with risperidone due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Risperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Levamlodipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
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) Concomitant use of levofloxacin and risperidone 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.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and risperidone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Levorphanol: (Moderate) Concomitant use of levorphanol with other CNS depressants such as risperidone can potentiate the effects of levorphanol on respiration, blood pressure, and alertness. Severe hypotension, respiratory depression, profound sedation, or coma may occur. Prior to concurrent use of levorphanol 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. Consider the patient's use of alcohol or illicit drugs. When concomitant treatment with levorphanol with another CNS depressant is necessary, reduce the dose of 1 or both drugs. The initial dose of levorphanol should be reduced by approximately 50% or more when levorphanol is used with another drug that may depress respiration.
Lidocaine; Epinephrine: (Major) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of risperidone. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal'. The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of risperidone. The use of other agents for vascular support is recommended when needed.
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) Use risperidone and lithium together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, it is advisable to monitor patients for neurotoxicity. Neuroleptic malignant syndrome (NMS) has been observed occasionally during concurrent use of lithium and either atypical or conventional antipsychotics. Additive extrapyramidal effects have also been noted. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Lithium has also been associated with QT prolongation.
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: (Major) Monitor ECG if lofexidine is coadministered with risperidone due to the potential for additive QT prolongation and torsade de pointes (TdP). Additionally, monitor for excessive hypotension and sedation during coadministration as lofexidine can potentiate the effects of CNS depressants. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Loperamide: (Moderate) Use risperidone and loperamide together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, TdP, and cardiac arrest.
Loperamide; Simethicone: (Moderate) Use risperidone and loperamide together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, TdP, and cardiac arrest.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with risperidone due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP), primarily in the overdose setting. (Moderate) Ritonavir may increase risperidone exposure; use together with caution and monitor for adverse effects of risperidone, including QT prolongation or other risperidone side effects. A decreased dosage of risperidone may be required. Risperidone is primarily metabolized by CYP2D6 and is also partially metabolized by CYP3A4; ritonavir inhibits both CYP2D6 and CYP3A4.
Lorazepam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Loxapine: (Major) Caution is advisable during concurrent use of loxapine and risperidone. Loxapine use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of loxapine and risperidone. 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: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and lumacaftor; ivacaftor and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Concomitant use may decrease risperidone exposure. Risperidone is a CYP3A substrate and combination lumacaftor; ivacaftor is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Lumacaftor; Ivacaftor: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and lumacaftor; ivacaftor and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Concomitant use may decrease risperidone exposure. Risperidone is a CYP3A substrate and combination lumacaftor; ivacaftor is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Lumateperone: (Moderate) Coadministration of antipsychotics, such as lumateperone and risperidone, 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) Co-administration of risperidone with lurasidone 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.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as risperidone. 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. Risperidone has been associated with a possible risk for QT prolongation and torsade de pointes. Reports of QT prolongation and torsade de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Maprotiline: (Moderate) Use risperidone and maprotiline together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. 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 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.
Mecamylamine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Meclizine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including meclizine. Additive drowsiness or other CNS effects may occur.
Mefloquine: (Moderate) Use risperidone and mefloquine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
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) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including meperidine. Hypotension, respiratory and/or CNS depression can be additive if meperidine is used concomitantly with risperidone.
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) Methadone has a known risk of QT prolongation and torsade de pointes (TdP) and a careful assessment of risks versus benefits should be performed before coadministration with drugs having a possible risk of QT prolongation and TdP such as risperidone. Methadone is particularly associated with an increased risk for QT prolongation and TdP at higher doses (e.g., 400 mg/day in adults). Concomitant use of CNS depressants, such as risperidone and methadone, can lead to additive CNS depression, hypotension, or coma. Prior to the use of methadone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, the patient's overall response to treatment, and the patient's use of alcohol or illicit drugs. In opioid-naive adults, initiate methadone at a dose of 2.5 mg every 12 hours in patients receiving other CNS depressants. Also consider using a lower dose of the CNS depressant.
Methohexital: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and barbiturates and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Additionally, monitor for unusual drowsiness and sedation during coadministration due to the risk for additive CNS depression. Concomitant use may decrease risperidone exposure and increase the risk for CNS depression. Risperidone is a CYP3A substrate, and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Methylphenidate Derivatives: (Moderate) Monitor for extrapyramidal symptoms (EPS) with concomitant use of risperidone and methylphenidate derivatives. Postmarketing cases of extrapyramidal symptoms (dystonia and dyskinesia) have been reported in patients when there was a change in dosage of either medication (increase or decrease in dosage) as well as with the initiation or discontinuation of either or both medications.
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: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of metoprolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving metoprolol concomitantly.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of metoprolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving metoprolol concomitantly.
Metronidazole: (Moderate) Concomitant use of metronidazole and risperidone 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) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Midostaurin: (Major) The concomitant use of midostaurin and risperidone may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram (ECG) monitoring. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Pooled data from controlled trials indicate there are no statistically significant differences in mean changes from baseline in ECG parameters including QT, QTc, and PR intervals when risperidone is compared to placebo. However, post-marketing reports of overdose indicate that QT prolongation and torsade de pointes have occurred.
Mifepristone: (Major) Concomitant use of risperidone and mifepristone 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.
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.
Mirtazapine: (Moderate) Concomitant use of mirtazapine and risperidone 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.
Mitotane: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and mitotane and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Concomitant use may decrease risperidone exposure. Risperidone is a CYP3A substrate and mitotane is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Mobocertinib: (Major) Concomitant use of mobocertinib and risperidone 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.
Molindone: (Major) Co-administration of risperidone with molindone 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.
Monoamine oxidase inhibitors: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of monoamine oxidase inhibitors (MAOIs) and risperidone due to the risk for additive hypotension and CNS depression.
Morphine: (Moderate) Concomitant use of morphine with other CNS depressants can potentiate the effects of morphine on respiration, blood pressure, and alertness; examples of other CNS depressants include risperidone. Prior to concurrent use of morphine 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. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with morphine, a reduced dosage of morphine and/or the CNS depressant is recommended; for extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours, extended-release capsules). Monitor patients for sedation and respiratory depression.
Morphine; Naltrexone: (Moderate) Concomitant use of morphine with other CNS depressants can potentiate the effects of morphine on respiration, blood pressure, and alertness; examples of other CNS depressants include risperidone. Prior to concurrent use of morphine 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. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with morphine, a reduced dosage of morphine and/or the CNS depressant is recommended; for extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours, extended-release capsules). Monitor patients for sedation and respiratory depression.
Moxifloxacin:< /strong> (Major) Concurrent use of risperidone and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Moxifloxacin has been associated with prolongation of the QT interval. Additionally, post-marketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded. Risperidone has also been associated with a possible risk for QT prolongation and/or TdP; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
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: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of nadolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving nadolol concomitantly.
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: (Moderate) Risperidone may cause orthostatic hypotension and thus enhance the hypotensive effects of nebivolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving nebivolol.
Nebivolol; Valsartan: (Moderate) Risperidone may cause orthostatic hypotension and thus enhance the hypotensive effects of nebivolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving nebivolol.
Nicardipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Nifedipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Nilotinib: (Major) Avoid the concomitant use of nilotinib and risperidone; significant prolongation of the QT interval may occur. If coadministration is required and the patient has risk factors for cardiac disease or arrhythmias, careful monitoring is recommended. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy. Risperidone has been associated with a possible risk for QT prolongation and/or TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Nimodipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Nirmatrelvir; Ritonavir: (Moderate) Ritonavir may increase risperidone exposure; use together with caution and monitor for adverse effects of risperidone, including QT prolongation or other risperidone side effects. A decreased dosage of risperidone may be required. Risperidone is primarily metabolized by CYP2D6 and is also partially metabolized by CYP3A4; ritonavir inhibits both CYP2D6 and CYP3A4.
Nisoldipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Non-Ionic Contrast Media: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents. Antipsychotics should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Nortriptyline: (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Ofloxacin: (Moderate) Concomitant use of ofloxacin and risperidone 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.
Olanzapine: (Moderate) Use risperidone and olanzapine 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. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Olanzapine; Fluoxetine: (Moderate) Monitor for an increase in risperidone-related adverse effects if concomitant use with fluoxetine is necessary and reduce risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, an anticipatory dosage decrease may be considered prior to initiation of fluoxetine. Concomitant use may increase risperidone exposure. 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. Risperidone is a CYP2D6 substrate and fluoxetine is a strong CYP2D6 inhibitor. Concomitant use has been observed to increase risperidone overall exposure by 2.5- to 2.8-fold. (Moderate) Use risperidone and olanzapine 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. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Olanzapine; Samidorphan: (Moderate) Use risperidone and olanzapine 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. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Oliceridine: (Major) Concomitant use of oliceridine with risperidone may cause excessive sedation and somnolence. Limit the use of oliceridine with risperidone 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) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Ondansetron: (Major) Concomitant use of risperidone and ondansetron 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. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose.
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.
Osilodrostat: (Moderate) Monitor ECGs in patients receiving osilodrostat with risperidone. Osilodrostat is associated with dose-dependent QT prolongation. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Osimertinib: (Major) Avoid coadministration of risperidone with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor for an increase in risperidone-related adverse reactions, periodically monitor ECGs for QT prolongation, and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Oxaliplatin: (Major) Closely monitor electrolytes and ECGs for QT prolongation if coadministration of risperidone with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP), primarily in the overdose setting. QT prolongation and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
Oxazepam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as risperidone, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking risperidone, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider using a lower risperidone dose. Monitor patients for sedation and respiratory depression.
Oxymorphone: (Moderate) Concomitant use of oxymorphone with other CNS depressants may produce additive CNS depressant effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur; examples of other CNS depressants include risperidone. Prior to concurrent use of oxymorphone 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. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with oxymorphone, a reduced dosage of oxymorphone (1/3 to 1/2 of the usual dose) and/or the CNS depressant is recommended. If the extended-release oxymorphone tablets are used concurrently with a CNS depressant, it is recommended to use an initial dosage of 5 mg PO every 12 hours. Monitor for sedation or respiratory depression.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking risperidone 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. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Pacritinib: (Major) Concomitant use of pacritinib and risperidone 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.
Paliperidone: (Major) Because paliperidone is the major active metabolite of risperidone, excessive paliperidone exposure is possible during concurrent use of the two drugs and coadministration is generally avoided. In addition, 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, such as risperidone. Coadministration of antipsychotics may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, or seizures.
Panobinostat: (Major) The coadministration of panobinostat with risperidone should be avoided if possible; both agents have a possible risk for QT prolongation and torsade de pointes. If coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is recommended.
Paroxetine: (Moderate) Monitor for an increase in risperidone-related adverse effects if concomitant use with paroxetine is necessary and reduce risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, an anticipatory dosage decrease may be considered prior to initiation of paroxetine. Concomitant use may increase risperidone exposure. Risperidone is a CYP2D6 substrate and paroxetine is a strong CYP2D6 inhibitor. Concomitant use has been observed to increase risperidone overall exposure by 3- to 9-fold.
Pasireotide: (Moderate) Use risperidone and pasireotide together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Pazopanib: (Major) Both risperidone and pazopanib have been associated with a possible risk for QT prolongation and torsade de pointes; therefore, caution is advisable during coadministration. If concurrent treatment is required and the patient has risk factors for cardiac disease or arrhythmias, close monitoring is recommended.
Pentamidine: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with risperidone include pentamidine.
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: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and barbiturates and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Additionally, monitor for unusual drowsiness and sedation during coadministration due to the risk for additive CNS depression. Concomitant use may decrease risperidone exposure and increase the risk for CNS depression. Risperidone is a CYP3A substrate, and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Perampanel: (Moderate) Co-administration of perampanel with CNS depressants, including ethanol, may increase CNS depression. The combination of perampanel (particularly at high doses) with ethanol has led to decreased mental alertness and ability to perform complex tasks (such as driving), as well as increased levels of anger, confusion, and depression; similar reactions should be expected with concomitant use of other CNS depressants, such as risperidone.
Perindopril; Amlodipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Perphenazine: (Moderate) Use risperidone and perphenazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also 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. Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Perphenazine; Amitriptyline: (Moderate) Use risperidone and perphenazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also 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. Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Phenobarbital: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and barbiturates and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Additionally, monitor for unusual drowsiness and sedation during coadministration due to the risk for additive CNS depression. Concomitant use may decrease risperidone exposure and increase the risk for CNS depression. Risperidone is a CYP3A substrate, and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and barbiturates and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Additionally, monitor for unusual drowsiness and sedation during coadministration due to the risk for additive CNS depression. Concomitant use may decrease risperidone exposure and increase the risk for CNS depression. Risperidone is a CYP3A substrate, and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Phenoxybenzamine: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Phentolamine: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Phenytoin: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and phenytoin and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Concomitant use may decrease risperidone exposure. Risperidone is a CYP3A substrate and phenytoin is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Consider the patient's underlying disease state(s) and additional potential risk factors if pimavanserin and risperidone coadministration cannot be avoided. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically.
Pimozide: (Contraindicated) Risperidone has a risk of QT prolongation and is contraindicated with pimozide. Concurrent use of pimozide with atypical agents may increase the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, 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.
Pindolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of pindolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving pindolol concomitantly.
Pioglitazone: (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.
Pioglitazone; Glimepiride: (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.
Pioglitazone; Metformin: (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.
Pitolisant: (Major) Avoid coadministration of pitolisant with risperidone as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking risperidone 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. Risperidone has been associated with a possible risk for QT prolongation and TdP, primarily in the overdose setting.
Posaconazole: (Moderate) Use risperidone and posaconazole together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Posaconazole has also been associated with QT prolongation and rare cases of TdP.
Potassium-sparing diuretics: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
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: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and risperidone. Concomitant use of pregabalin with risperidone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
Prilocaine; Epinephrine: (Major) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of risperidone. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal'. The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of risperidone. The use of other agents for vascular support is recommended when needed.
Primaquine: (Moderate) Use risperidone and primaquine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Primaquine has also been associated with QT prolongation.
Primidone: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and barbiturates and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Additionally, monitor for unusual drowsiness and sedation during coadministration due to the risk for additive CNS depression. Concomitant use may decrease risperidone exposure and increase the risk for CNS depression. Risperidone is a CYP3A substrate, and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Procainamide: (Major) Risperidone should be used cautiously and with close monitoring with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically.
Prochlorperazine: (Moderate) Use risperidone and prochlorperazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also 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. Prochlorperazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Promethazine: (Moderate) Use risperidone and promethazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also 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. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Promethazine; Dextromethorphan: (Moderate) Use risperidone and promethazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also 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. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Promethazine; Phenylephrine: (Moderate) Use risperidone and promethazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also 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. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Propafenone: (Major) Concomitant use of risperidone and propafenone 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.
Propranolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of propranolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving propranolol concomitantly.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of propranolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving propranolol concomitantly.
Protriptyline: (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Pseudoephedrine; Triprolidine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone 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 risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Quazepam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Quetiapine: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with risperidone include quetiapine. Quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Additionally, according to the manufacturer, no significant kinetic drug interactions were identified when quetiapine was coadministered with haloperidol or risperidone.
Quinidine: (Major) Concomitant use of risperidone and fixed-dose combination quinidine; dextromethorphan is contraindicated. Avoid concomitant use of risperidone and quinidine alone if possible; use increases the risk for QT/QTc prolongation and torsade de pointes (TdP) and is expected to increase risperidone exposure. 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 an increase in risperidone-related adverse effects and reduce risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, an anticipatory dosage decrease may be considered prior to initiation of quinidine. Risperidone is a CYP2D6 substrate, and quinidine is a strong CYP2D6 inhibitor. Concomitant use with other strong CYP2D6 inhibitors increased risperidone overall exposure by 2.5- to 9-fold.
Quinine: (Major) Concurrent use of quinine and risperidone should be avoided if possible due to an increased risk for QT prolongation and torsade de pointes (TdP). If coadministration is required and the patient has risk factors for cardiac disease or arrhythmias, close monitoring is recommended.
Quizartinib: (Major) Concomitant use of quizartinib and risperidone 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.
Ranitidine: (Moderate) Although dosage adjustments are not necessary, patients receiving concurrent treatment with risperidone and ranitidine should be monitored for risperidone-induced side effects or extrapyramidal symptoms. Pharmacokinetic data indicate that increased exposure to risperidone and its active metabolite occurs during use of ranitidine. This interaction is thought to be the result of inhibition of CYP3A4, one of the isoenzymes responsible for the metabolism of risperidone.
Ranolazine: (Moderate) Use risperidone and ranolazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs concurrent use may result in additive QT prolongation.
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) Use risperidone and relugolix together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) Use risperidone and relugolix together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Remifentanil: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including remifentanil.
Remimazolam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
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) Avoid coadministration of ribociclib with risperidone if possible due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner and risperidone has also been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with risperidone if possible due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner and risperidone has also been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Rifampin: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and rifampin and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Concomitant use may decrease risperidone exposure. Risperidone is a CYP3A substrate and rifampin is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Rifapentine: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and rifapentine and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Concomitant use may decrease risperidone exposure. Risperidone is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
Rilpivirine: (Moderate) Use risperidone and rilpivirine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Ritonavir: (Moderate) Ritonavir may increase risperidone exposure; use together with caution and monitor for adverse effects of risperidone, including QT prolongation or other risperidone side effects. A decreased dosage of risperidone may be required. Risperidone is primarily metabolized by CYP2D6 and is also partially metabolized by CYP3A4; ritonavir inhibits both CYP2D6 and CYP3A4.
Rolapitant: (Major) Coadministration of risperidone, a CYP2D6 substrate, and rolapitant, a CYP2D6 inhibitor, may increase plasma concentrations of risperidone. The inhibitory effect of rolapitant is expected to persist beyond 28 days for an unknown duration. When oral risperidone is given with a CYP2D6 inhibitor, the dose of risperidone should be reduced; do not exceed 8 mg/day PO in adults. When initiating therapy, titrate risperidone slowly. Upon discontinuation of the CYP2D6 inhibitor, the risperidone dose should be re-evaluated and increased if necessary. For the long-acting injection, the current adult dosage should be re-evaluated when a CYP2D6 inhibitor is initiated or discontinued. When initiation of a CYP2D6 inhibitor is considered, patients may be placed on a lower dose of injectable risperidone 2 to 4 weeks prior to initiation to adjust for the expected increase in risperidone plasma concentrations. For patients receiving a 25 mg dose, it is recommended to maintain the 25 mg dose upon initiation of the CYP2D6 inhibitor unless clinical judgment warrants lowering the dose to 12.5 mg or interrupting risperidone therapy. The efficacy of the 12.5 mg dose has not been evaluated in clinical trials. When injectable risperidone is initiated in patients already receiving a CYP2D6 inhibitor, a starting dose of 12.5 mg can be considered. Exposure to another CYP2D6 substrate, following a single dose of rolapitant increased about 3-fold on Days 8 and Day 22. The inhibition of CYP2D6 persisted on Day 28 with a 2.3-fold increase in the CYP2D6 substrate concentrations, the last time point measured.
Romidepsin: (Moderate) Monitor ECG and electrolytes if risperidone is coadministered with romidepsin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Romidepsin has also been reported to prolong the QT interval.
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.
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) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as TdP. Avoid coadministration. If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations.
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: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and barbiturates and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Additionally, monitor for unusual drowsiness and sedation during coadministration due to the risk for additive CNS depression. Concomitant use may decrease risperidone exposure and increase the risk for CNS depression. Risperidone is a CYP3A substrate, and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
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) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with risperidone is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
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) Concomitant use of sertraline and risperidone 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 sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
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) In general, do not initiate treatment with siponimod in patients receiving risperidone due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP). Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
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 risperidone 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) Use risperidone and solifenacin together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined.
Sorafenib: (Major) Avoid coadministration of sorafenib with risperidone due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Sorafenib is also associated with QTc prolongation.
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 sotalol and risperidone 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.
St. John's Wort, Hypericum perforatum: (Moderate) Monitor for a decrease in risperidone efficacy during concomitant use of risperidone and St. John's Wort and increase risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, supplemental oral risperidone may be required. Concomitant use may decrease risperidone exposure. Risperidone is a CYP3A substrate and St. John's Wort is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced risperidone overall exposure by 50%.
S tiripentol: (Major) Monitor for excessive sedation and somnolence during coadministration of stiripentol and risperidone. CNS depressants can potentiate the effects of stiripentol.
Sufentanil: (Moderate) Concomitant use of sufentanil with other CNS depressant, such as risperidone, can potentiate sufentanil-induced CNS and cardiovascular effects and the duration of these effects. A dose reduction of one or both drugs may be warranted.
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) Use risperidone and sunitinib together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Sunitinib can also prolong the QT interval.
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) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with risperidone. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes. Reports of QT prolongation and torsade de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Tamoxifen: (Moderate) Concomitant use of tamoxifen and risperidone 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) Additive CNS depressive effects are expected if tapentadol is used in conjunction with other CNS depressants. Severe hypotension, profound sedation, coma, or respiratory depression may occur. Prior to concurrent use of tapentadol 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. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with tapentadol, a reduced dosage of tapentadol and/or the CNS depressant is recommended. If the extended-release tapentadol tablets are used concurrently with a CNS depressant, it is recommended to use an initial tapentadol dose of 50 mg PO every 12 hours. Monitor patients for sedation and respiratory depression.
Telavancin: (Moderate) Use risperidone and telavancin together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Telavancin has also been associated with QT prolongation.
Telmisartan; Amlodipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Temazepam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Terazosin: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Terbinafine: (Moderate) Monitor for an increase in risperidone-related adverse effects if concomitant use with terbinafine is necessary and reduce risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, an anticipatory dosage decrease may be considered prior to initiation of terbinafine. Concomitant use may increase risperidone exposure. Risperidone is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with other strong CYP2D6 inhibitors increased risperidone overall exposure by 2.5- to 9-fold.
Tetrabenazine: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc such as risperidone. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. In addition, the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
Thiazide diuretics: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Thioridazine: (Contraindicated) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer primarily in the overdosage setting. However, due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of risperidone and thioridazine is considered contraindicated.
Thiothixene: (Major) Co-administration of risperidone with thiothixene 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.
Timolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of timolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving timolol concomitantly.
Tipranavir: (Moderate) Monitor for an increase in risperidone-related adverse effects if concomitant use with tipranavir is necessary and reduce risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, an anticipatory dosage decrease may be considered prior to initiation of tipranavir. Concomitant use may increase risperidone exposure. Risperidone is a CYP2D6 substrate and tipranavir is a strong CYP2D6 inhibitor. Concomitant use with other strong CYP2D6 inhibitors increased risperidone overall exposure by 2.5- to 9-fold.
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.
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) Use risperidone and tolterodine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers.
Toremifene: (Major) Avoid coadministration of risperidone with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Risperidone has also been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP), primarily in the setting of overdose.
Torsemide: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Tramadol: (Major) Concurrent use of tramadol and risperidone should be avoided if possible due to a possible increased risk of seizures. Seizures have been reported in patients receiving monotherapy with tramadol or antipsychotics at recommended doses. In addition, due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally-acting medications such as tramadol.
Tramadol; Acetaminophen: (Major) Concurrent use of tramadol and risperidone should be avoided if possible due to a possible increased risk of seizures. Seizures have been reported in patients receiving monotherapy with tramadol or antipsychotics at recommended doses. In addition, due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally-acting medications such as tramadol.
Trandolapril; Verapamil: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Trazodone: (Major) Concomitant use of trazodone and risperidone 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.
Treprostinil: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Triazolam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
Triclabendazole: (Moderate) Concomitant use of triclabendazole and risperidone 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) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Trifluoperazine: (Moderate) Use risperidone and trifluoperazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also 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. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Trimipramine: (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Triprolidine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Triptorelin: (Major) Avoid coadministration of triptorelin with risperidone due to the risk of reduced efficacy of triptorelin; QT prolongation may also occur. Risperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
Valproic Acid, Divalproex Sodium: (Minor) Coadministration of risperidone and valproate may result in a minor increase in peak plasma concentrations of valproic acid; however, dosage adjustments of valproic acid are not recommended. In one evaluation, concomitant administration of risperidone 4 mg/day and valproate 1,000 mg/day resulted in a 20% increase in valproate peak plasma concentration (Cmax) and there was no effect on the pre-dose or average plasma concentrations and exposure (AUC) of valproate. The mechanism of this interaction is not known.
Vandetanib: (Major) Avoid coadministration of vandetanib with risperidone due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Vardenafil: (Moderate) Concomitant use of vardenafil and risperidone 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.
Vasodilators: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Vemurafenib: (Major) Vemurafenib and risperidone have been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP). Additionally, coadministration of risperidone, a CYP2D6 substrate, with CYP2D6 inhibitors may increase plasma concentrations of risperidone; however, a clinically significant kinetic interaction with vemurafenib is unlikely because vemurafenib is only a mild inhibitor of CYP2D6.
Venlafaxine: (Moderate) Concomitant use of venlafaxine and risperidone 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.
Verapamil: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Viloxazine: (Moderate) Monitor for an increase in risperidone-related adverse effects if concomitant use of viloxazine is necessary. Concomitant use may increase risperidone exposure. Viloxazine is a weak CYP2D6 inhibitor and risperidone is a CYP2D6 substrate.
Voclosporin: (Moderate) Concomitant use of voclosporin and risperidone may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with risperidone. If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. Clarithromycin is associated with an established risk for QT prolongation and TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Voriconazole: (Moderate) Use risperidone and voriconazole together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Voriconazole has also been associated with QT prolongation and rare cases of TdP.
Vorinostat: (Moderate) Use risperidone and vorinostat together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Vorinostat therapy is also associated with a risk of QT prolongation.
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.
Ziconotide: (Moderate) Risperidone is a CNS depressant medication that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Ziprasidone: (Major) The benefits and risks of combining antipsychotics should be considered prior to treatment initiation. Both ziprasidone and risperidone have been associated with a possible risk for QT prolongation and torsade de pointes. In addition, coadministration of antipsychotics may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited.
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.

PERSERIS/UZEDY Subcutaneous Inj Susp ER: 0.14mL, 0.21mL, 0.28mL, 0.35mL, 0.42mL, 0.56mL, 0.7mL, 50mg, 75mg, 90mg, 100mg, 120mg, 125mg, 150mg, 200mg, 250mg
Risperdal Consta/Rykindo Intramuscular Inj Pwd F/Susp ER: 12.5mg, 25mg, 37.5mg, 50mg
Risperdal M-Tab/Risperidone Oral Tab Orally Dis: 0.25mg, 0.5mg, 1mg, 2mg, 3mg, 4mg
Risperdal/Risperidone Oral Sol: 1mg, 1mL
Risperdal/Risperidone Oral Tab: 0.25mg, 0.5mg, 1mg, 2mg, 3mg, 4mg

Adults

Oral dosage forms: 16 mg/day PO for schizophrenia; 6 mg/day PO for bipolar disorder. Risperdal Consta or Rykindo: 50 mg depot IM every 2 weeks for schizophrenia or bipolar disorder. Perseris: 120 mg depot subcutaneously once monthly for schizophrenia. Uzedy: 125 mg depot subcutaneously once monthly or 250 mg depot subcutaneously once every 2 months for schizophrenia.

Geriatric

Oral dosage forms: 16 mg/day PO for schizophrenia; 6 mg/day PO for bipolar disorder. Risperdal Consta or Rykindo: 50 mg depot IM every 2 weeks for schizophrenia or bipolar disorder. Perseris: 120 mg depot subcutaneously once monthly for schizophrenia. Uzedy: 125 mg depot subcutaneously once monthly or 250 mg depot subcutaneously once every 2 months for schizophrenia.

Adolescents

6 mg/day PO for schizophrenia or bipolar I disorder; 3 mg/day PO for autistic disorder; 0.06 mg/kg/day PO has been suggested for the treatment of tics or severe behavior disorders associated with Tourette's or ADHD; safety and efficacy of injectables have not been established.

Children

10 to 12 years: 6 mg/day PO for bipolar I disorder; 3 mg/day PO for autistic disorder; 0.06 mg/kg/day PO has been suggested in developmental disability with severe disruptive behaviors; safety and efficacy of injectables have not been established.
5 to 9 years: 3 mg/day PO for autistic disorder; 0.06 mg/kg/day PO has been suggested in developmental disability with severe disruptive behaviors; safety and efficacy of injectables have not been established.
1 to 4 years: Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Although the exact mechanism of action of antipsychotics is unknown, it has been proposed that central blockade of dopamine D2 in the mesolimbic pathway targets the positive symptoms of schizophrenia (e.g., hallucinations, delusions). Optimal blockade is within the range of 65% to 75% of D2 receptors, leading to effectiveness while preserving safety. The receptor binding profile of many conventional antipsychotics (e.g., haloperidol, fluphenazine) involves a preferred affinity for D2 receptors over serotonin receptors, whereas the receptor binding profile of some atypical antipsychotics (such as risperidone) involves a high affinity for 5-HT2A receptor blockade. It has been theorized that antagonism of serotonin in the prefrontal cortex leads to an increase in dopamine release thereby creating the potential for improvement in the negative symptoms (e.g., blunted affect, social withdrawal) and cognitive deficits observed in schizophrenia. It should be noted that modulation of serotonin receptors alone does not have an antipsychotic effect. Antipsychotic drugs appear to have neuroplastic effects, including synaptic plasticity (remodeling of synapses and development of new neuron connections) and neurogenesis (new neuron development), which may partially explain the delay in some therapeutic effects of antipsychotics.
 
Dopamine blockade by antipsychotics in the nigrostriatal pathway of the brain is thought to cause extrapyramidal symptoms (EPS) such as pseudoparkinsonism, dystonic reactions, and akathisia. It has been suggested that blockade of 5-HT2A receptors leads to increased output of dopaminergic neurons into the striatum, decreasing the likelihood of extrapyramidal reactions. Dopamine receptor blockade in the tuberoinfundibular tract results in prolactin release, with the potential for hyperprolactinemia and its adverse clinical effects. The likelihood of developing hyperprolactinemia is generally related to the potency of the individual antipsychotic to block D2 receptors. Thus, based on its D2 receptor binding profile, risperidone has a higher propensity for causing prolactin elevations than most other atypical antipsychotics.
 
Risperidone exhibits strong antagonist activity at alpha-1 receptors, which likely contributes to adverse cardiovascular effects such as orthostatic hypotension, which may be associated with dizziness, syncope, and reflex tachycardia. The alpha-1 blocking effect is also thought to be responsible for priapism, a potentially severe adverse reaction which has occurred during post-marketing use of the drug. High affinity at H-1 histamine receptors has also been demonstrated, which partially accounts for adverse effects such as sedation and weight gain. Risperidone has low to moderate affinity for serotonin 5-HT1A, 5-HT1C, and 5-HT1D receptors and a weak affinity for dopamine D1 receptors and haloperidol-sensitive sigma binding sites. There is no affinity for cholinergic or beta-adrenergic receptors.

Risperidone is administered orally, as an extended-release intramuscular injection (Risperdal Consta or Rykindo), and as an extended-release subcutaneous injection (Perseris or Uzedy). The main metabolic pathway is through hydroxylation of risperidone to 9-hydroxyrisperidone by the enzyme CYP2D6. A minor metabolic pathway is through N-dealkylation. The clinical effect results from the combined concentrations of the total active moiety, risperidone plus 9-hydroxyrisperidone; both forms are equally active. Risperidone is highly protein bound (90%) and its major active metabolite, 9-hydroxyrisperidone, is 77% protein bound. Risperidone and 9-hydroxyrisperidone are preferentially distributed to the frontal cortex and striatum in the brain, where tissue half-lives are longer than in the plasma. The oral half-life is approximately 3 hours in normal (extensive) CYP2D6 metabolizers. Excretion of metabolites is mainly renal, with a small amount excreted in the feces; about 70% of an oral dose is eliminated in the urine. Intramuscular and subcutaneous formulations of risperidone have large volumes of distribution because they are depot extended-release injections; each injection type displays unique pharmacokinetic characteristics.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP2D6, CYP3A4, P-glycoprotein (P-gp)
Risperidone is metabolized to an equally active metabolite, 9-hydroxyrisperidone. Risperidone is a primary substrate of CYP2D6. Drug CYP2D6 inhibitors may produce interactions that reduce the metabolism of risperidone to 9-hydroxyrisperidone would increase the plasma concentrations of risperidone and lower the concentrations of 9-hydroxyrisperidone. These types of interactions have not been specifically studied with the depot injectable dosage forms. With oral risperidone, the concomitant use of a potent CYP2D6 results in a reduced maximal daily oral risperidone dose limit. Risperidone is also a substrate of CYP3A4, but to a lesser degree than CYP2D6. Potent CYP3A inducers cause a decrease in the combined plasma concentrations of risperidone and 9-hydroxyrisperidone, which could lead to decreased efficacy and which may necessitate risperidone dose adjustments. Inhibitors of CYP3A do not result in risperidone pharmacokinetic changes that are clinically significant. Risperidone is a weak inhibitor of CYP2D6 in vitro; but studies have determined that risperidone is not expected to substantially inhibit the clearance of drugs that are metabolized by CYP2D6. Risperidone has a strong affinity for P-gp.

Oral Route

Risperidone is administered orally as tablets, orally disintegrating tablets, or as an oral solution. Dosages of the orally disintegrating tablets and oral solution are bioequivalent to comparable dosages of the original-formulation tablets. Absorption is complete; these dosage forms of risperidone can be administered without regard to meals. Peak plasma concentrations are achieved within 1 to 2 hours. Plasma concentrations are dose-proportional for risperidone and its active metabolite.

Intramuscular Route

Risperdal Consta (risperidone) extended-release intramuscular injection: Risperdal Consta may be injected into the gluteal or deltoid muscle. These routes of administration are considered bioequivalent and interchangeable. After a single IM (gluteal) depot injection of risperidone, the main release of the drug starts from 3 weeks onward, is maintained from 4 to 6 weeks, and subsides by 7 weeks after the IM injection. Therefore, oral antipsychotic supplementation should be given during the first 3 weeks of treatment with risperidone to maintain therapeutic concentrations until the main release of risperidone has begun. The combination of the release profile and the dosage regimen (IM depot injections every 2 weeks) of risperidone results in sustained therapeutic concentrations. Steady-state plasma concentrations are reached after 4 injections and are maintained for 4 to 6 weeks after the last injection. Plasma concentrations of risperidone, 9-hydroxyrisperidone (the major metabolite), and risperidone plus 9-hydroxyrisperidone are linear over the dosing range of 25 mg to 50 mg. The apparent half-life of risperidone plus 9-hydroxyrisperidone after Risperdal Consta administration is 3 to 6 days and is related to the erosion of the microspheres and subsequent absorption of risperidone; no accumulation occurs with chronic use and the elimination phase is complete approximately 7 to 8 weeks after the last IM depot injection.
Rykindo (risperidone) extended-release intramuscular injection: Rykindo is injected into gluteal muscle only. After a single IM injection, the release profile consists of an initial release of risperidone followed by a stable release phase of 2 to 4 weeks. The median time to peak concentration (Tmax) of risperidone and 9-hydroxyrisperidone combined are 14 and 17 days after administration of 25 mg and 50 mg doses of Rykindo, respectively. Systemic exposures (AUC and Cmax) of the active moiety increase in a dose proportional manner across the dosing range from 12.5 mg to 50 mg. The combination of the release profile and dosing regimen (IM injection every 2 weeks) results in sustained concentrations within the dosing interval (every 2 weeks). Steady-state plasma concentration levels are reached after 2 injections and can be maintained for 2 to 3 weeks after the last injection. The apparent half-life of active moiety following Rykindo administration is 3 to 6 days and associated with a monoexponential decline in plasma concentrations after a single dose. This half-life is related to the erosion of the sterile powder and subsequent absorption of risperidone after Rykindo IM administration.

Subcutaneous Route

Perseris (risperidone) extended-release injectable suspension: Perseris may be injected into the abdomen or back of the upper arm. Perseris contains risperidone in a liquid delivery system. Following subcutaneous injection, it forms a depot that provides sustained plasma concentrations of risperidone over the monthly dosing interval. After a single dose injection, Perseris shows 2 absorption peaks, 4 to 6 hours post-injection and 10 to 14 days post-injection, representing the initial release of the drug during the depot formation process and the second peak associated with the slow release of risperidone from the subcutaneous depot. For both 9-hydroxyrisperidone and total active moiety (risperidone + 9-hydroxyrisperidone), the median time to maximum concentrations (Tmax) of the first peak ranged from 4 to 48 hours and the second peak ranged from 7 to 11 days. After a single-dose injection, maximum plasma concentrations of risperidone were reached in 4 to 6 hours and approached steady-state concentrations. After repeated doses separated by 28 days for up to 4 injections following oral risperidone, steady-state concentrations were reached by the end of the second injection for risperidone, 9-hydroxyrisperidone, and total active moiety, and were maintained for 4 weeks after the last Perseris injection. Total active moiety concentrations reached clinically relevant levels after the first injection without use of a loading dose or any supplemental oral risperidone. Following multiple doses, plasma exposure of risperidone, 9-hydroxyrisperidone, and the total active moiety increased in a dose proportional manner over the dose range of 60 to 120 mg. When plasma exposures at steady-state were compared, 90 mg once monthly of the subcutaneous depot injection corresponded to 3 mg/day of oral risperidone and 120 mg of the subcutaneous depot injection corresponded to 4 mg/day of oral risperidone. Following a single Perseris injection, the apparent terminal half-life of risperidone ranges between 9 and 11 days on average. This half-life is related to the slow release of risperidone from the subcutaneous depot and subsequent absorption of risperidone into the systemic circulation. The mean apparent terminal half-life ranges between 8 and 9 days for both 9-hydroxyrisperidone and total active moiety.
Uzedy (risperidone) extended-release injectable suspension: Uzedy may be injected into the abdomen or back of the upper arm. Steady-state levels of risperidone and 9-hydroxyrisperidone were approached within 2 months of Uzedy initiation for all doses. Steady-state plasma exposure values of risperidone, 9-hydroxyrisperidone, and the combination following once monthly administration of Uzedy are approximately 2 to 2.5-fold higher than single dose exposure, while values for Uzedy administered once every 2 months are about 1.5-fold higher than the respective single dose exposure. After administration of Uzedy, plasma levels of risperidone, 9-hydroxyrisperidone, and the combination increase in a dose-proportional manner. The average exposure values over the dosing period are comparable for Uzedy administered once monthly and once every 2 months at corresponding doses. Following both once monthly (doses of 50 mg to 125 mg) and once every 2 month dosing (doses 100 mg to 250 mg), the mean exposure of risperidone and 9-hydroxyrisperidone combined of Uzedy corresponds to that of oral risperidone (2 to 5 mg per day) administered over an equivalent dosing period. The mean apparent half-life of UZEDY ranges between 14 and 22 days for risperidone, 9-hydroxyrisperidone, and risperidone and 9- hydroxyrisperidone combined.

Pregnancy

When considering the use of risperidone during pregnancy, the possibility of risperidone-related adverse outcomes in the fetus or neonate should be weighed against the risks of an untreated maternal psychiatric condition, which may include hospitalization, relapse, suicide, and increased adverse perinatal outcomes (e.g., pre-term birth). A prospective observational study of women (n = 6) treated with risperidone demonstrated placental passage of risperidone and its metabolite paliperidone. A retrospective cohort study from a Medicaid database of 9,258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects. There was a small increase in major birth defects and cardiac malformations in a subgroup of 1,566 women exposed to risperidone during their first trimester of pregnancy; however, there is no mechanism of action to explain the increased malformation rate, and the overall available data from published epidemiologic studies of pregnant women exposed to atypical antipsychotics have not established a drug-associated risk of birth defects, miscarriages, or adverse maternal or fetal outcomes. There is a human case report of agenesis of the corpus callosum occurring in utero. Neonates exposed to antipsychotics during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity and have ranged from self-limited to those requiring intensive care unit support and prolonged hospitalization. Neonates exhibiting signs or symptoms of extrapyramidal effects or withdrawal should be carefully monitored. The knowledge about long-term neurobehavioral effects in offspring is limited for all antipsychotic agents and requires further investigation. According to the American Psychiatric Association treatment guidelines for schizophrenia, consider pregnancy testing in women of childbearing potential prior to initiation of an antipsychotic. It is not known if antipsychotics, through their effect on prolactin, would affect labor or delivery. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to risperidone; information about the registry can be obtained at womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry or by calling 1-866-961-2388.