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Haldol
Classes
First Generation Antipsychotics
Administration
May administer with food to minimize GI irritation.
Oral concentrate solution:
The concentrate can be administered directly from the calibrated pipette, or the solution can be mixed with a beverage or food prior to administration. However, the concentrate may precipitate if mixed with coffee or tea.
Avoid skin contact with solution during administration as contact dermatitis may occur.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Verify selection of proper injectable product prior to administration.
Instructions for opening injection ampules:
Before breaking the ampule, lightly tap the top of the ampule with your finger until all fluid moves to the bottom of the ampule.
Hold the ampule between index finger and thumb with colored point (located at the base of the neck of the ampule) facing you.
Position index finger of the other hand to support the neck of the ampule. Position the thumb so that it covers the colored point and is parallel to the colored ring (located above the colored point).
Keeping the thumb on the colored point and with the index fingers close together, apply firm pressure on the colored point in the direction of the arrow to snap the ampule open.
IV Push (haloperidol lactate immediate-release injection solution only):
NOTE: IV administration of the lactate injection is not approved by the FDA in any population. Therefore, benefit to risk should be carefully assessed. Higher than recommended doses of any haloperidol formulation and IV administration appear to be associated with a higher risk of QT prolongation and torsade de pointes.
If haloperidol is administered IV, the ECG should be closely monitored for QT prolongation and arrhythmias.
SLOW IV push/infusion over several minutes is recommended to decrease the risk of hypotension, oversedation, extrapyramidal effects, and other adverse effects. Slow IV infusion over 30 to 45 minutes has also been reported for loading dose administration.
Carefully monitor efficacy and tolerability (sedation or other adverse effects) periodically for the first several days.
Switch to oral therapy, if needed, as soon as practical. When switching parenteral therapy to oral therapy, and depending on the patient's clinical status, the first oral dose should be given within 12 to 24 hours following the last parenteral dose.
Haloperidol lactate immediate-release injection solution:
Administer by intramuscular (IM) injection.
Carefully monitor efficacy and tolerability (sedation or other adverse effects) periodically for the first several days.
The parenteral dose administered in the preceding 24 hours may be used to approximate the total daily dose required for subsequent parenteral treatment.
Switch to oral therapy, if needed, as soon as practical. When switching parenteral therapy to oral therapy, and depending on the patient's clinical status, the first oral dose should be given within 12 to 24 hours following the last parenteral dose.
Haloperidol decanoate depot injection in oil:
Do NOT administer intravenously. Administer by deep intramuscular (IM) injection ONLY.
The volume per injection site should not exceed 3 mL.
A 21-gauge needle is recommended.
Adverse Reactions
seizures / Delayed / 0-1.0
akinesia / Delayed / 2.8
torticollis / Delayed / Incidence not known
tardive dyskinesia / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
aplastic anemia / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
retinopathy / Delayed / Incidence not known
visual impairment / Early / Incidence not known
hepatic failure / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
vasculitis / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
bronchospasm / Rapid / Incidence not known
laryngeal edema / Rapid / Incidence not known
laryngospasm / Rapid / Incidence not known
stroke / Early / Incidence not known
torsade de pointes / Rapid / Incidence not known
ventricular tachycardia / Early / Incidence not known
cardiac arrest / Early / Incidence not known
ventricular fibrillation / Early / Incidence not known
SIADH / Delayed / Incidence not known
water intoxication / Delayed / Incidence not known
neuroleptic malignant syndrome / Delayed / Incidence not known
rhabdomyolysis / Delayed / Incidence not known
neonatal abstinence syndrome / Early / Incidence not known
constipation / Delayed / 1.0-10.0
hallucinations / Early / 0-1.0
akathisia / Delayed / 10.0
dystonic reaction / Delayed / 10.0
pseudoparkinsonism / Delayed / 10.0
hypertonia / Delayed / 10.0
dyskinesia / Delayed / Incidence not known
nystagmus / Delayed / Incidence not known
trismus / Delayed / Incidence not known
confusion / Early / Incidence not known
euphoria / Early / Incidence not known
depression / Delayed / Incidence not known
anemia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
neutropenia / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
ejaculation dysfunction / Delayed / Incidence not known
galactorrhea / Delayed / Incidence not known
hyperprolactinemia / Delayed / Incidence not known
impotence (erectile dysfunction) / Delayed / Incidence not known
infertility / Delayed / Incidence not known
priapism / Early / Incidence not known
urinary retention / Early / Incidence not known
osteopenia / Delayed / Incidence not known
blurred vision / Early / Incidence not known
cataracts / Delayed / Incidence not known
dysphagia / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
cholestasis / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
hypotension / Rapid / Incidence not known
QT prolongation / Rapid / Incidence not known
sinus tachycardia / Rapid / Incidence not known
edema / Delayed / Incidence not known
orthostatic hypotension / Delayed / Incidence not known
dyspnea / Early / Incidence not known
hyponatremia / Delayed / Incidence not known
hyperthermia / Delayed / Incidence not known
heat intolerance / Early / Incidence not known
withdrawal / Early / Incidence not known
hyperammonemia / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
hypoglycemia / Early / Incidence not known
contact dermatitis / Delayed / Incidence not known
xerostomia / Early / 1.0-10.0
drowsiness / Early / 5.3-5.3
headache / Early / 2.8-2.8
abdominal pain / Early / 2.8-2.8
hypersalivation / Early / 1.2-1.2
tremor / Early / 10.0
hyperkinesis / Delayed / 10.0
lethargy / Early / 10.0
restlessness / Early / 10.0
weight gain / Delayed / 10.0
agitation / Early / Incidence not known
anxiety / Delayed / Incidence not known
insomnia / Early / Incidence not known
vertigo / Early / Incidence not known
purpura / Delayed / Incidence not known
fever / Early / Incidence not known
infection / Delayed / Incidence not known
mastalgia / Delayed / Incidence not known
menstrual irregularity / Delayed / Incidence not known
gynecomastia / Delayed / Incidence not known
libido decrease / Delayed / Incidence not known
amenorrhea / Delayed / Incidence not known
dysmenorrhea / Delayed / Incidence not known
menorrhagia / Delayed / Incidence not known
retinal pigment changes / Delayed / Incidence not known
nausea / Early / Incidence not known
vomiting / Early / Incidence not known
weight loss / Delayed / Incidence not known
rash / Early / Incidence not known
urticaria / Rapid / Incidence not known
injection site reaction / Rapid / Incidence not known
polydipsia / Early / Incidence not known
hypothermia / Delayed / Incidence not known
acneiform rash / Delayed / Incidence not known
photosensitivity / Delayed / Incidence not known
alopecia / Delayed / Incidence not known
diaphoresis / Early / Incidence not known
maculopapular rash / Early / Incidence not known
Boxed Warning
Geriatric patients may be more susceptible than younger adults to the adverse effects of haloperidol, including tardive dyskinesia, dystonias, orthostatic hypotension, prolonged QT interval, and falls and fractures. Initiate treatment with lower doses followed by careful dosage titration and close monitoring. Antipsychotics are not approved for the treatment of dementia-related psychosis in geriatric patients and use of haloperidol in this population should be avoided if possible due to an increase in morbidity and mortality in geriatric patients with dementia receiving some 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. Haloperidol should be used with caution in any patient with risk factors for cerebrovascular adverse reactions, such as those with cerebrovascular disease. The Beers Criteria consider antipsychotics to be potentially inappropriate medications 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 haloperidol 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 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, or rationale for continued use. Refer to the OBRA guidelines for complete information.
Common Brand Names
Haldol, Haldol Decanoate
Dea Class
Rx
Description
High-potency oral and parenteral conventional antipsychotic structurally related to droperidol
Oral formulation and immediate-release intramuscular injection FDA-approved for treating schizophrenia and Tourette's Disorder; immediate-release IM formulation is effective for acute agitation in hospitalized settings
An intramuscular depot injection is available for schizophrenic patients requiring prolonged antipsychotic therapy
As with all antipsychotics, there is an increased risk of death in elderly patients treated for dementia-related psychosis; IV administration is not FDA-approved and is associated with an increased risk of QT prolongation and torsade de pointes (TdP)
Dosage And Indications
Initially, 0.5 mg to 2 mg PO given 2 to 3 times per day in patients with moderate symptomatology or in debilitated patients. For severe, chronic, or refractory target symptoms, initiate with 3 to 5 mg PO given 2 to 3 times per day. Optimal response in geriatric patients is usually obtained with more gradual dosage adjustments and at lower dosages than what is required for younger adults. Adjust the dose based on response and tolerability. After the initial therapeutic response is achieved, slowly reduce to the lowest effective maintenance dose. The Patient Outcome Research Team (PORT) consensus guidelines recommend a dosage range for acute therapy of 6 mg/day to 20 mg/day and for maintenance therapy the PORT guidelines recommend a dosage range of 6 mg/day to 12 mg/day. Max: 100 mg/day PO.
0.5 to 5 mg/day PO; may administer in 2 or 3 divided doses. Although a pediatric dose for children and adolescents weighing more than 40 kg is not specified, FDA-approved labeling recommends 0.5 to 2 mg PO 2 to 3 times per day as an initial dose for adult patients with moderate symptomatology, or 3 to 5 mg PO 2 to 3 times per day for adult patients with severe, chronic, or treatment-resistant symptoms. Higher doses may be required in some cases to achieve prompt control. Patients who remain severely disturbed or inadequately controlled may require dosage adjustment. Max: 100 mg/day PO for severe refractory cases. After a therapeutic response is achieved, the dosage should be slowly reduced to the lowest effective maintenance dose.
0.5 mg/day PO initially; may administer in 2 or 3 divided doses. If clinically warranted, the dose may be increased by 0.5 mg increments at 5 to 7 day intervals until the desired therapeutic effect is obtained. The usual dose range is 0.05 mg/kg/day to 0.15 mg/kg/day PO; severe cases may require higher doses. A maximum effective dose has not been established; however, there is little evidence that behavior improvement is further enhanced with dosages above 6 mg/day PO. After a therapeutic response is achieved, the dosage should be slowly reduced to the lowest effective maintenance dose.
Patients should be stabilized on an immediate-release antipsychotic before considering a conversion to haloperidol decanoate for treating schizophrenic patients who require prolonged parenteral therapy. In order to reduce the possibility of an unexpected adverse reaction to haloperidol decanoate, it is recommended that patients be treated with and tolerate short-acting haloperidol. ADULTS PREVIOUSLY MAINTAINED ON LOW ORAL DOSES OF ANTIPSYCHOTICS (E.G., UP TO THE EQUIVALENT OF 10 MG/DAY OF ORAL HALOPERIDOL) OR DEBILITATED ADULTS: The initial recommended IM depot dose is 10 to 15 times the previous antipsychotic dose in oral haloperidol equivalents, with subsequent adjustments based on response and tolerability. ADULTS PREVIOUSLY MAINTAINED ON HIGH ORAL DOSES OF ANTIPSYCHOTICS (E.G., GREATER THAN THE EQUIVALENT OF 10 MG/DAY OF HALOPERIDOL) FOR WHOM A LOW DOSE APPROACH RISKS DECOMPENSATION OR IN PATIENTS WHOSE LONG-TERM HALOPERIDOL USE HAS RESULTED IN TOLERANCE TO THE DRUG: The initial suggested IM depot dose is 20 times the previous antipsychotic dose in oral haloperidol equivalents, with downward titration on subsequent monthly doses. For all patients, the initial injection should not exceed 100 mg regardless of the previous antipsychotic dose requirements. If conversion requires an initial dose of more than 100 mg, the dose should be divided into 2 injections consisting of an initial injection not to exceed 100 mg followed by the balance in 3 to 7 days. The usual monthly maintenance range is 10 to 15 times the previous daily oral dose; however, the maintenance dosage should be titrated upward or downward based upon response and tolerability to reach the optimal regimen for each patient. The Patient Outcome Research Team (PORT) consensus guidelines recommend a maintenance dosage range of 50 mg to 200 mg every 4 weeks. With careful monitoring, haloperidol decanoate can be supplemented with oral haloperidol during dosage adjustments or symptom exacerbation. Usual Max: Clinical experience at doses greater than 450 mg/month IM has been limited.
Patients should be stabilized on an immediate-release antipsychotic before considering a conversion to haloperidol decanoate for treating schizophrenic patients who require prolonged parenteral therapy. In order to reduce the possibility of an unexpected adverse reaction to haloperidol decanoate, it is recommended that patients be treated with and tolerate short-acting haloperidol. The initial and usual monthly IM maintenance dose range in geriatric patients is 10 to 15 times the previous antipsychotic dose in oral haloperidol equivalents, with titration upward or downward based on response and tolerability. The initial injection should not exceed 100 mg regardless of the previous antipsychotic dose requirements. If conversion requires an initial dose of more than 100 mg, the dose should be divided into 2 injections consisting of an initial injection not to exceed 100 mg followed by the balance in 3 to 7 days. The Patient Outcome Research Team (PORT) consensus guidelines recommend a maintenance dosage range of 50 mg to 200 mg every 4 weeks. With careful monitoring, haloperidol decanoate can be supplemented with oral haloperidol during dosage adjustments or symptom exacerbation. Usual Max: Clinical experience at doses greater than 450 mg/month IM has been limited.
0.5 mg/day PO initially; may administer in 2 or 3 divided doses. If clinically warranted, the dose may be increased by 0.5 mg increments at 5 to 7 day intervals until the desired therapeutic effect is obtained. The usual dose range is 0.05 to 0.075 mg/kg/day PO. A maximum effective dose has not been established; however, there is little evidence that behavior improvement is further enhanced with dosages above 6 mg/day PO. Patients should be assessed periodically to determine the need for continued therapy; short-term treatment may be sufficient in some patients.
0.5 to 2 mg PO 2 to 3 times per day initially for adults with moderate symptoms, or 3 to 5 mg PO 2 to 3 times per day for adults with severe, chronic, or treatment-resistant symptoms. Titrate to effectiveness and tolerance. After a therapeutic response is achieved, gradually reduce to the lowest effective maintenance dose. Usual average dose: 15 mg/day PO. Max: 100 mg/day PO. The American Academy of Neurology practice guideline states that haloperidol is probably more likely than placebo to reduce tic severity; however, there is insufficient evidence to determine the efficacy of haloperidol relative to other antipsychotics used to treat tics.
0.25 to 0.5 mg/day PO initially, slowly titrated by 0.25 to 0.5 mg increments at 5 to 7-day intervals until the desired therapeutic effect is obtained. The daily dosage may be given in 2 or 3 divided doses. Clinical guidelines suggest the usual dosage range is 1 to 4 mg/day PO. Max if weight 40 kg or less: 15 mg/day PO. Although a dose for adolescents weighing more than 40 kg is not specified, FDA-approved labeling recommends 0.5 to 2 mg PO 2 to 3 times per day initially for adults with moderate symptoms, or 3 to 5 mg PO 2 to 3 times per day for adults with severe, chronic, or treatment-resistant symptoms. After a therapeutic response is achieved, gradually reduce to the lowest effective maintenance dose. The American Academy of Neurology practice guideline states that haloperidol is probably more likely than placebo to reduce tic severity; however, there is insufficient evidence to determine the efficacy of haloperidol relative to other antipsychotics used to treat tics.
0.25 to 0.5 mg/day PO initially, slowly titrated by 0.25 to 0.5 mg increments at 5 to 7-day intervals until the desired therapeutic effect is obtained. The daily dosage may be given in 2 or 3 divided doses. FDA approved labeling states the usual dose range is 0.05 to 0.075 mg/kg/day PO; this coincides closely with the usual dose range of 1 to 4 mg/day PO that clinical guidelines suggest. Max: 15 mg/day PO. After a therapeutic response is achieved, gradually reduce to the lowest effective maintenance dose. The American Academy of Neurology practice guideline states that haloperidol is probably more likely than placebo to reduce tic severity; however, there is insufficient evidence to determine the efficacy of haloperidol relative to other antipsychotics used to treat tics.
2 to 10 mg IM every 20 to 30 minutes as needed. The FDA-approved dose is 2 to 5 mg IM every hour as needed, although every 4 to 8 hours as needed may be satisfactory. Max: 20 mg/day.
0.025 to 0.075 mg/kg/dose (Usual dose: 2 to 5 mg/dose) IM every 20 to 30 minutes as needed. Consider one-fourth to one-half of the usual daily dose if the child is currently taking haloperidol and it is not the usual dose time. Max: 15 mg/day.
0.025 to 0.075 mg/kg/dose (Usual dose: 0.5 to 2 mg/dose) IM every 20 to 30 minutes as needed. Consider one-fourth to one-half of the usual daily dose if the child is currently taking haloperidol and it is not the usual dose time. Max: 6 mg/day.
5 to 10 mg PO every hour as needed. Max: 20 mg/day.
0.025 to 0.075 mg/kg/dose (Usual dose: 2 to 5 mg/dose) PO every hour as needed. Consider one-fourth to one-half of the usual daily dose if the child is currently taking haloperidol and it is not the usual dose time. Max: 15 mg/day.
0.025 to 0.075 mg/kg/dose (Usual dose: 0.5 to 2 mg/dose) PO every hour as needed. Consider one-fourth to one-half of the usual daily dose if the child is currently taking haloperidol and it is not the usual dose time. Max: 6 mg/day.
Data are limited. In one small study of children 10 years and older, haloperidol was initiated at 0.25 mg/day PO at bedtime and titrated over 1 week to 0.5 mg twice daily. Thereafter, the dose was adjusted as clinically indicated. The mean daily dose was 1.3 mg and the range was 1 to 1.5 mg/day PO. In a separate study enrolling children 2.6 to 7.2 years of age, the optimal dose was 1.7 mg/day PO. Haloperidol was associated with significant improvement in withdrawal and stereotypy in children 4.5 years and older. Data from clinical trials assessing dyskinesias in young children (2 to 8 years of age) receiving long-term treatment (e.g., 6 months) with haloperidol indicate that tardive dyskinesia or withdrawal dyskinesias have occurred in approximately 20% to 34% of patients. The majority of cases have been withdrawal dyskinesias which were reversible. Due to the risk of extrapyramidal effects, haloperidol is generally reserved for children who have not responded to or are intolerant to therapy with an atypical antipsychotic.
2 mg to 5 mg IM every 4 to 6 hours has been used as rescue treatment. Haldol is not a preferred agent due to the side effect profile; guidelines specify the use of olanzapine as a preferred alternative for breakthrough nausea/vomiting due to chemotherapy.
The following have been recommended in the literature for adults. MILD AGITATION: Single doses of 0.5 to 2 mg PO or IM. Repeat doses should be based on clinical response. MODERATE AGITATION: Single doses of 5 to 10 mg PO or IM. Repeat doses are based on clinical response. SEVERE AGITATION: Single doses of 10 mg or more PO or IM. Repeat doses are based on clinical response.
The IV route has been used in critically ill patients; the best quality consensus reviews available recommend intermittent dosing; well controlled clinical trials are lacking. The usual initial dose is 2 mg to 10 mg IV. Many experts begin with a loading regimen of 2 mg IV, followed by repeat doses every 15 to 20 minutes while agitation persists. Thereafter once delirium is controlled, may repeat a dose every 4 to 6 hours, as needed, for a few days. Dosage reductions can be attempted, with tapering doses over several days. A typical taper regimen for the first day is one-half of the previous 24-hour total dose, given in divided doses. Haloperidol has been given occasionally as a continuous IV infusion (3 to 25 mg/hour IV); there are limited data to support infusions. Haloperidol lactate injection is not FDA-approved for intravenous (IV) administration. Cases of QT prolongation and torsade de pointes (TdP) have occurred, including fatalities, during IV use. ECG monitoring is recommended during IV administration. The risk increases with higher dosages (e.g., 20 mg/dose or more).
Limited data available, particularly in young children. A loading dose of 0.15 to 0.25 mg IV given slowly over 30 to 45 minutes, followed by a maintenance dose of 0.05 to 0.5 mg/kg/24 hours IV (divided and given every 8 hours) has been described in several case reports/series (n = 39; age range: 3 months to 17 years). One small case series (n = 6; age range: 9 to 15 years) reported no loading dose but a modal individual maintenance dose of 0.5 mg IV. Maximum dose is unclear in pediatric patients; do not exceed 20 mg/day, the FDA-approved maximum parenteral dose in adults. Treatment of delirium often consisted of psychosocial, environmental, and, if warranted, pharmaceutical intervention. In general, IV haloperidol was reserved for patients with psychomotor agitation that was acutely threatening to their health. Pharmaceutical intervention lasted from a few hours to days and, in most cases, was stopped or tapered off during hospitalization or subsequently in an outpatient setting. Discontinue pharmacotherapy as soon as the acute phase of delirium has resolved. Haloperidol lactate injection is not FDA-approved for intravenous (IV) administration. Cases of QT prolongation and torsade de pointes (TdP) have occurred, including fatalities, during IV use. ECG monitoring is recommended during IV administration.
2 mg to 5 mg IM has been effective in treating intractable hiccups from various causes. Haloperidol has less potential for producing hypotension as compared to chlorpromazine.
Initially, 0.25 mg or 0.5 mg PO 1 to 2 times per day. Increase by no more than 0.5 mg every 4 to 7 days if needed, in divided doses as necessary. Sedative effects may be minimized in some patients by using a single daily dose at bedtime. Antipsychotics are not FDA-approved for this indication and the labeling of all antipsychotics contains a boxed warning noting an increased risk of death in geriatric patients being treated for behavioral problems associated with dementia. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of antipsychotics in long-term care facility (LTCF) residents with dementia-related behavioral symptoms. OBRA Max: 2 mg/day PO in residents meeting OBRA criteria for treatment, except when documentation is provided showing that higher doses are necessary to maintain or improve the resident's functional status. In addition, the facility must attempt a gradual dose reduction (GDR) in 2 separate quarters, at least 1 month apart, within the first year of admission to the facility or after the facility has initiated an antipsychotic, unless clinically contraindicated. After the first year, a GDR must be attempted annually unless clinically contraindicated. The GDR may be considered clinically contraindicated if the target symptoms returned or worsened after the most recent GDR attempt within the facility and the physician has documented justification for why attempting additional dose reductions at that time would likely impair the resident's function or increase distressed behavior.
†Indicates off-label use
Dosing Considerations
Specific guidelines for dosage adjustments in hepatic impairment are not available; however, reduced dosages or avoidance is advisable in patients with significant liver dysfunction. Haloperidol is extensively metabolized in the liver.
Renal ImpairmentSpecific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
Drug Interactions
Abarelix: (Contraindicated) Since abarelix can cause QT prolongation, abarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation including haloperidol. Prescribers need to weigh the potential benefits and risks of abarelix use in patients that are taking drugs that can cause QT prolongation.
Abiraterone: (Moderate) Monitor for an increase in haloperidol-related adverse reactions if coadministration with abiraterone is necessary. Haloperidol is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. In pharmacokinetic studies, mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with drugs characterized as inhibitors of CYP2D6.
Acebutolol: (Moderate) Haloperidol should be used cautiously with acebutolol due to the possibility of additive hypotension.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as diphenhydramine, a sedating H1-blocker. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with haloperidol may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of haloperidol could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If haloperidol is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Haloperidol is a moderate inhibitor of CYP2D6.
Acetaminophen; Chlorpheniramine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with haloperidol may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of haloperidol could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If haloperidol is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Haloperidol is a moderate inhibitor of CYP2D6.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Acetaminophen; Diphenhydramine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as diphenhydramine, a sedating H1-blocker. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with haloperidol may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of haloperidol could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If haloperidol is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Haloperidol is a moderate inhibitor of CYP2D6.
Acetaminophen; Oxycodone: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as opiate agonists. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Acetaminophen; Phenylephrine: (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Acetaminophen; Pseudoephedrine: (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Acetazolamide: (Moderate) Caution is advisable during concurrent use of haloperidol and acetazolamide as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol.
Acrivastine; Pseudoephedrine: (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Adagrasib: (Major) Avoid concomitant use of adagrasib and haloperidol due to the potential for increased haloperidol exposure, haloperidol-related side effects, and additive risk for QT/QTc prolongation and torsade de pointes (TdP). If use is necessary, monitor for haloperidol-related adverse effects and consider taking additional steps to minimize the risk for QT prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Haloperidol is a CYP3A substrate, adagrasib is a strong CYP3A inhibitor, and both medications have been associated with QT interval prolongation. The intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
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: (Minor) Haloperidol can potentiate the actions of other CNS depressants, such as opiate agonists, Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Alfuzosin: (Moderate) Caution is advisable when combining haloperidol concurrently with alfuzosin. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Alfuzosin may also prolong the QT interval in a dose-depndent manner.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension.
Alprazolam: (Moderate) Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and CYP3A4 substrates such as alprazolam. Until more data are available, it is advisable to closely monitor for adverse events when alprazolam is coadministered with haloperidol. Concomitant administration of alprazolam with CNS-depressant drugs including antipsychotics can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.
Amantadine: (Moderate) Although the mechanism of amantadine is not clear, it may potentiate the actions of dopamine. Since haloperidol is a dopamine antagonist, this drug is best avoided when possible in patients with Parkinson's disease who require amantadine therapy.
Amifampridine: (Major) Carefully consider the need for concomitant treatment with haloperidol 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. Haloperidol may increase the risk of seizures.
Amiloride: (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension. (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Amiodarone: (Major) QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval. In addition, haloperidol is a substrate for CYP3A4 and CYP2D6. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and inhibitors of CYP3A4 or CYP2D6. Therefore, it is advisable to closely monitor for adverse events when haloperidol is co-administered with drugs that inhibit CYP3A4 and CYP2D6 and prolong the QT interval, such as amiodarone. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with haloperidol. Amisulpride causes dose- and concentration- dependent QT prolongation. QT prolongation and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Amlodipine: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Amlodipine; Atorvastatin: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Amlodipine; Benazepril: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Amlodipine; Celecoxib: (Moderate) A dosage adjustment may be warranted for haloperidol if coadministered with celecoxib due to the potential for celecoxib to enhance the exposure and toxicity of haloperidol. Celecoxib is a CYP2D6 inhibitor, and haloperidol is a CYP2D6 substrate. (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Amlodipine; Olmesartan: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension. (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Amlodipine; Valsartan: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension. (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension. (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension. (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Amobarbital: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as barbiturates. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Amoxapine: (Moderate) Use caution during co-administration of amoxapine and antipsychotics. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. Clinically significant anticholinergic activity may also be seen with loxapine, olanzapine, and clozapine. In addition, amoxapine is metabolized by CYP2D6. Haloperidol is an inhibitor of hepatic CYP2D6, and coadministration with amoxapine may lead to elevated amoxapine serum concentrations.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Concurrent use of clarithromycin and haloperidol should be avoided if possible. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval. Because clarithromycin is also associated with an increased risk for QT prolongation and TdP, the need to coadminister clarithromycin with drugs known to prolong the QT interval should be done with a careful assessment of risks versus benefits. Clarithromycin is an inhibitor of CYP3A4. Elevated haloperidol concentrations occurring through inhibition of CYP3A4 or CYP2D6 may increase the risk of adverse effects, including QT prolongation.
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 haloperidol.
Angiotensin II receptor antagonists: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Angiotensin-converting enzyme inhibitors: (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as anxiolytics, sedatives, and hypnotics, and they should be used cautiously in combination.
Apalutamide: (Moderate) Monitor for decreased efficacy of haloperidol if coadministration with apalutamide is necessary. Haloperidol is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased haloperidol plasma concentrations by a mean of 70% and increased mean scores on the Brief Psychiatric Rating Scale from baseline.
Apomorphine: (Major) Avoid use of haloperidol with apomorphine when possible. Concurrent use may result in additive CNS depression and QT prolongation. The effectiveness of either agent may be decreased due to opposing effects on dopamine; consider if an atypical antipsychotic would be a suitable alternative to haloperidol. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. 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 if coadministration cannot be avoided.
Aprepitant, Fosaprepitant: (Major) Use caution if haloperidol and aprepitant, fosaprepitant are used concurrently and monitor for an increase in haloperidol-related adverse effects, including QT prolongation and torsade de pointes (TdP), for several days after administration of a multi-day aprepitant regimen. Haloperidol is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of haloperidol. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Aripiprazole: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of haloperidol. Patients receiving both a CYP3A inhibitor plus haloperidol may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Additionally, consider taking steps to minimize the risk of QT/QTc interval prolongation and torsade de pointes (TdP), such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Concomitant use may increase the risk for CNS depression, QT prolongation and torsade de pointes (TdP), and may increase aripiprazole exposure and the risk for other aripiprazole-related adverse effects. Aripiprazole is a CYP2D6 and CYP3A substrate; haloperidol is a weak CYP2D6 inhibitor. Both medications have been associated with QT prolongation. The intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Arsenic Trioxide: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include haloperidol.
Artemether; Lumefantrine: (Major) Artemether; lumefantrine is an inhibitor of and haloperidol is partially metabolized by the CYP2D6 isoenzyme; therefore, coadministration may lead to increased haloperidol concentrations. Furthermore, although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Concomitant use of artemether; lumefantrine with drugs that may prolong the QT interval, such as haloperidol, should be avoided. Consider ECG monitoring if haloperidol must be used with or after artemether; lumefantrine treatment.
Articaine; Epinephrine: (Major) Use of epinephrine to treat droperidol or haloperidol -induced hypotension can result in a paradoxical lowering of blood pressure due to droperidol's alpha-blocking effects. Avoid using epinephrine concurrently with droperidol and haloperidol.
Asenapine: (Major) Asenapine has been associated with QT prolongation. According to the manufacturer, asenapine should not be used with other agents also known to have this effect (e.g., haloperidol).
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as barbiturates. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Orphenadrine has mild anticholinergic activity. Concomitant use of orphenadrine and haloperidol may worsen schizophrenic symptoms. Tardive dyskinesia may also develop.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with haloperidol may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of haloperidol could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If haloperidol is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Haloperidol is a moderate inhibitor of CYP2D6.
Aspirin, ASA; Oxycodone: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as opiate agonists. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Atazanavir: (Moderate) 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 the listed drugs and an increased potential for QT prolongation or other adverse effects. Serious and/or life-threatening drug interactions could potentially occur between atazanavir and these drugs. Haloperidol is metabolized by CYP3A4 and with the potential to cause QT prolongation. Avoid use of atazanavir with haloperidol when possible. Downward dosage adjustment of haloperidol may be necessary.
Atazanavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with haloperidol as there is a potential for elevated haloperidol concentrations. Haloperidol is a CYP3A4 substrate and CYP2D6 substrate. Cobicistat is a strong inhibitor of CYP3A4 and an inhibitor of CYP2D6. (Moderate) 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 the listed drugs and an increased potential for QT prolongation or other adverse effects. Serious and/or life-threatening drug interactions could potentially occur between atazanavir and these drugs. Haloperidol is metabolized by CYP3A4 and with the potential to cause QT prolongation. Avoid use of atazanavir with haloperidol when possible. Downward dosage adjustment of haloperidol may be necessary.
Atenolol: (Moderate) Haloperidol should be used cautiously with atenolol due to the possibility of additive hypotension.
Atenolol; Chlorthalidone: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension. (Moderate) Haloperidol should be used cautiously with atenolol due to the possibility of additive hypotension.
Atomoxetine: (Moderate) Concomitant use of atomoxetine and haloperidol 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 intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Atropine; Difenoxin: (Moderate) Haloperidol can potentiate the actions of other CNS depressants, such as opiate agonists, Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Azilsartan: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Azilsartan; Chlorthalidone: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension. (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Azithromycin: (Major) Avoid coadministration of azithromycin with haloperidol 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. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Barbiturates: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as barbiturates. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with haloperidol. 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. QT prolongation and TdP have also been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Belladonna; Opium: (Moderate) Haloperidol can potentiate the actions of other CNS depressants, such as opiate agonists, Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with haloperidol may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with haloperidol 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 haloperidol, reduce initial dosage and titrate to clinical response. If haloperidol is initiated a patient taking an opioid agonist, use a lower initial dose of haloperidol and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Additive adverse effects resulting from cholinergic blockade may occur when hyoscyamine is administered concomitantly with haloperidol.
Benztropine: (Moderate) Advise patients to promptly report gastrointestinal complaints, fever, or heat intolerance when benztropine is used with drugs with either anticholinergic activity or antidopaminergic activity (example is haloperidol). Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
Betaxolol: (Moderate) Haloperidol should be used cautiously with betaxolol due to the possibility of additive hypotension.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and haloperidol 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 intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and haloperidol 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 intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Bisoprolol: (Moderate) Haloperidol should be used cautiously with bisoprolol due to the possibility of additive hypotension.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension. (Moderate) Haloperidol should be used cautiously with bisoprolol due to the possibility of additive hypotension.
Brexpiprazole: (Major) Caution is advisable during concurrent use of brexpiprazole with other antipsychotics such as haloperidol. Brexpiprazole is partially metabolized by CYP2D6 and haloperidol is a moderate inhibitor of CYP2D6. The manufacturer of brexpiprazole recommends that the brexpiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving a moderate to strong inhibitor of CYP3A4 in combination with a moderate to strong inhibitor of CYP2D6. Therefore, if haloperidol is used in combination with brexpiprazole and a moderate to strong CYP3A4 inhibitor, the brexpiprazole dose should be adjusted and the patient should be carefully monitored for brexpiprazole-related adverse reactions. The risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, or seizures may be increased during combined use of haloperidol and brexpiprazole; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is deemed necessary. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Brimonidine; Timolol: (Moderate) Haloperidol should be used cautiously with timolol due to the possibility of additive hypotension.
Bromocriptine: (Major) Avoid concurrent use of haloperidol and bromocriptine when possible. Haloperidol results in a decreased efficacy of bromocriptine. The prolactin-lowering effect of bromocriptine is antagonized; the elevation in prolactin levels produced by haloperidol persists with chronic administration. Until more data are available, it is advisable to closely monitor for adverse events when these medications must be co-administered.
Brompheniramine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Brompheniramine; Phenylephrine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Brompheniramine; Pseudoephedrine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Coadministration of glycopyrrolate with haloperidol may decrease haloperidol serum concentrations, which may lead to worsening of psychiatric symptoms and the development of tardive dyskinesia. If coadministration is necessary, closely monitor patient.
Bumetanide: (Moderate) Caution is advisable during concurrent use of haloperidol and loop diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension.
Bupivacaine; Epinephrine: (Major) Use of epinephrine to treat droperidol or haloperidol -induced hypotension can result in a paradoxical lowering of blood pressure due to droperidol's alpha-blocking effects. Avoid using epinephrine concurrently with droperidol and haloperidol.
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 haloperidol and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Haloperidol 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 haloperidol 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 haloperidol and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Haloperidol 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 haloperidol and buprenorphine is necessary, consider a dose reduction of one or both drugs. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Bupropion: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. In addition, bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Coadministration of bupropion with medications that are metabolized by the CYP2D6 isoenzyme, such as haloperidol, should be approached with caution. Dosage reductions of haloperidol may be needed. Conversely, if bupropion therapy is discontinued, the antipsychotic dosage may need to be increased in some patients.
Bupropion; Naltrexone: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. In addition, bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Coadministration of bupropion with medications that are metabolized by the CYP2D6 isoenzyme, such as haloperidol, should be approached with caution. Dosage reductions of haloperidol may be needed. Conversely, if bupropion therapy is discontinued, the antipsychotic dosage may need to be increased in some patients.
Buspirone: (Moderate) Monitor for adverse effects, such as excess sedation and QT prolongation, during coadministration of buspirone and haloperidol. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and buspirone. Elevated haloperidol concentrations may increase the risk of adverse effects, including QT prolongation.
Butabarbital: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as barbiturates. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Butalbital; Acetaminophen: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as barbiturates. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Butalbital; Acetaminophen; Caffeine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as barbiturates. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with haloperidol may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of haloperidol could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If haloperidol is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Haloperidol is a moderate inhibitor of CYP2D6. (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as barbiturates. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with haloperidol may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of haloperidol could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If haloperidol is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Haloperidol is a moderate inhibitor of CYP2D6. (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as barbiturates. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Butorphanol: (Moderate) Concomitant use of butorphanol with other CNS depressants can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation. If a CNS depressant 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 haloperidol due to mutually antagonistic effects on dopaminergic function. The dopamine antagonist action of haloperidol 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 haloperidol.
Cabotegravir; Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with haloperidol as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Candesartan: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension. (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and haloperidol. CNS depressants can potentiate the effects of cannabidiol.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension.
Carbamazepine: (Major) Carbamazepine may potentially accelerate the hepatic metabolism of haloperidol. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with haloperidol.
Carbidopa; Levodopa: (Major) Due to opposing effects on central dopaminergic activity, haloperidol and levodopa may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to haloperidol. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Carbidopa; Levodopa; Entacapone: (Major) Due to opposing effects on central dopaminergic activity, haloperidol and COMT inhibitors may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to haloperidol. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. (Major) Due to opposing effects on central dopaminergic activity, haloperidol and levodopa may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to haloperidol. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Carbinoxamine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Cariprazine: (Major) Avoid use of these drugs together due to duplicative therapeutic effects and additive risks for drowsiness, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. Cariprazine, like other antipsychotics, has the potential to impair judgment, thinking, or motor skills. The use of cariprazine with other antipsychotic agents, such as haloperidol, would be expected to have additive risks for pharmacologic effects and adverse reactions. 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 combined use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Carteolol: (Moderate) Haloperidol should be used cautiously with carteolol due to the possibility of additive hypotension.
Carvedilol: (Moderate) Haloperidol should be used cautiously with carvedilol due to the possibility of additive hypotension. In addition, haloperidol inhibits CYP 2D6 and may increase plasma concentrations of carvedilol.
Celecoxib: (Moderate) A dosage adjustment may be warranted for haloperidol if coadministered with celecoxib due to the potential for celecoxib to enhance the exposure and toxicity of haloperidol. Celecoxib is a CYP2D6 inhibitor, and haloperidol is a CYP2D6 substrate.
Celecoxib; Tramadol: (Major) Haloperidol can competitively inhibit the metabolism of tramadol by CYP2D6. Concurrent use of haloperidol and tramadol increases plasma levels of tramadol and decreases the concentration of the active tramadol metabolite. This may lead to decreased analgesic effects of tramadol and possibly increased tramadol-induced side effects, including seizures, due to increased tramadol concentrations and the decrease in seizure threshold caused by haloperidol. Additive CNS depression may also be seen with the concomitant use of tramadol and haloperidol. (Moderate) A dosage adjustment may be warranted for haloperidol if coadministered with celecoxib due to the potential for celecoxib to enhance the exposure and toxicity of haloperidol. Celecoxib is a CYP2D6 inhibitor, and haloperidol is a CYP2D6 substrate.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and haloperidol. Concurrent use may result in additive CNS depression.
Central-acting adrenergic agents: (Moderate) Disturbances of orthostatic regulation (e.g., orthostatic hypotension, dizziness, fatigue) and additive sedation may occur in patients receiving concomitant clonidine and antipsychotics. Also, based on observations in patients in a state of alcoholic delirium, high intravenous doses of clonidine may increase the arrhythmogenic potential (QT prolongation, ventricular fibrillation) of high intravenous doses of haloperidol. A causal relationship and relevance for clonidine oral tablets have not been established.
Ceritinib: (Major) Avoid coadministration of ceritinib with haloperidol if possible due to the risk of QT prolongation; plasma concentrations of haloperidol may also increase. 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. Monitor for haloperidol-related adverse reactions. Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent prolongation of the QT interval. Haloperidol is a CYP3A4 substrate that has caused QT prolongation and torsade de pointes (TdP) during treatment; excessive doses (particularly in the overdose setting) or IV administration may be associated with a higher risk. In clinical trials, mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with CYP3A4 inhibitors.
Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with haloperidol should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with haloperidol should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Cetrorelix: (Moderate) Antipsychotics cause hyperprolactinemia and should not be administered concomitantly with cetrorelix since hyperprolactinemia downregulates the number of pituitary GnRH receptors.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Chloramphenicol: (Moderate) Chloramphenicol is an inhibitor of CYP3A4, one of the isoenzymes responsible for the metabolism of haloperidol. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and inhibitors of CYP3A4. Until more data are available, it is advisable to closely monitor for adverse events when these medications are co-administered.
Chlorcyclizine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Chlordiazepoxide: (Moderate) Haloperidol can potentiate the actions of other CNS depressants, such as benzodiazepines, Caution should be exercised with simultaneou
Chlordiazepoxide; Amitriptyline: (Moderate) Haloperidol can potentiate the actions of other CNS depressants, such as benzodiazepines, Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Chlordiazepoxide; Clidinium: (Moderate) Haloperidol can potentiate the actions of other CNS depressants, such as benzodiazepines, Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Chloroquine: (Major) Avoid coadministration of chloroquine with haloperidol due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. QT prolongation and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Chlorothiazide: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension.
Chlorpheniramine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with haloperidol may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of haloperidol could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If haloperidol is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Haloperidol is a moderate inhibitor of CYP2D6. (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Chlorpheniramine; Dextromethorphan: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with haloperidol may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of haloperidol could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If haloperidol is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Haloperidol is a moderate inhibitor of CYP2D6. (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with haloperidol may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of haloperidol could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If haloperidol is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Haloperidol is a moderate inhibitor of CYP2D6. (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Chlorpheniramine; Phenylephrine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Chlorpheniramine; Pseudoephedrine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Chlorpromazine: (Major) Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). Other antipsychotics associated with a possible risk for QT prolongation and TdP which should be avoided during treatment with chlorpromazine include haloperidol. 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.
Chlorthalidone: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension.
Chlorthalidone; Clonidine: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension. (Moderate) Disturbances of orthostatic regulation (e.g., orthostatic hypotension, dizziness, fatigue) and additive sedation may occur in patients receiving concomitant clonidine and antipsychotics. Also, based on observations in patients in a state of alcoholic delirium, high intravenous doses of clonidine may increase the arrhythmogenic potential (QT prolongation, ventricular fibrillation) of high intravenous doses of haloperidol. A causal relationship and relevance for clonidine oral tablets have not been established.
Ciprofloxacin: (Moderate) Concomitant use of ciprofloxacin and haloperidol 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 intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Cisapride: (Contraindicated) Cisapride is associated with QT prolongation and torsade de pointes (TdP) and cisapride is contraindicated for use in patients taking other drugs known to prolong the QT interval. Both QT prolongation and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Because of the potential for torsade de pointes (TdP), use of cisapride with haloperidol is contraindicated.
Citalopram: (Major) Coadministration of citalopram and haloperidol should be avoided. Citalopram causes dose-dependent QT interval prolongation, and haloperidol is associated with a possible risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. In addition, because of the potential risk and severity of serotonin syndrome or neuroleptic malignant syndrome-like reactions, caution should be observed when administering citalopram with drugs that are dopamine antagonists such as haloperidol. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. In addition, citalopram mildly inhibits the CYP2D6. This can result in increased concentrations of some drugs metabolized via the same pathway, including haloperidol. Patients receiving these combinations should be monitored for the emergence of serotonin syndrome, neuroleptic malignant syndrome-like reactions, or other adverse effects.
Clarithromycin: (Major) Concurrent use of clarithromycin and haloperidol should be avoided if possible. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval. Because clarithromycin is also associated with an increased risk for QT prolongation and TdP, the need to coadminister clarithromycin with drugs known to prolong the QT interval should be done with a careful assessment of risks versus benefits. Clarithromycin is an inhibitor of CYP3A4. Elevated haloperidol concentrations occurring through inhibition of CYP3A4 or CYP2D6 may increase the risk of adverse effects, including QT prolongation.
Clemastine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Clobazam: (Major) A dosage reduction of CYP2D6 substrates, such as haloperidol, may be necessary during co-administration of clobazam. Limited in vivo data suggest that clobazam is an inhibitor of CYP2D6. Elevated concentrations of haloperidol occurring through inhibition of CYP2D6 may increase the risk of adverse effects, including QT prolongation and torsade de pointes. Clobazam, a benzodiazepine, may cause drowsiness or other CNS effects which may be potentiated during concurrent use of conventional antipsychotics including phenothiazines, haloperidol, loxapine, thiothixene, or molindone. Antipsychotics may lower the seizure threshold and reduce the effectiveness of clobazam as an anticonvulsant.
Clofazimine: (Moderate) Concomitant use of clofazimine and haloperidol 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 intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Clonazepam: (Moderate) Haloperidol can potentiate the actions of other CNS depressants, such as benzodiazepines, Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Clonidine: (Moderate) Disturbances of orthostatic regulation (e.g., orthostatic hypotension, dizziness, fatigue) and additive sedation may occur in patients receiving concomitant clonidine and antipsychotics. Also, based on observations in patients in a state of alcoholic delirium, high intravenous doses of clonidine may increase the arrhythmogenic potential (QT prolongation, ventricular fibrillation) of high intravenous doses of haloperidol. A causal relationship and relevance for clonidine oral tablets have not been established.
Clorazepate: (Moderate) Haloperidol can potentiate the actions of other CNS depressants, such as benzodiazepines, Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Clozapine: (Moderate) Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Haloperidol is also associated with a possible risk for QT prolongation and 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. 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. Clozapine is metabolized by CYP1A2, CYP3A4, and CYP2D6. Antipsychotic drugs known to inhibit the activity of CYP2D6 include haloperidol. Elevated plasma concentrations of clozapine occurring through inhibition of CYP1A2, CYP3A4, or CYP2D6 may potentially increase the risk of life-threatening arrhythmias, sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. According to the manufacturer, patients receiving clozapine in combination with an inhibitor of CYP2D6 should be monitored for adverse reactions. Consideration should be given to reducing the clozapine dose if necessary. If the inhibitor is discontinued after dose adjustments are made, monitor for lack of clozapine effectiveness and consider increasing the clozapine dose if necessary.
Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with haloperidol as there is a potential for elevated haloperidol concentrations. Haloperidol is a CYP3A4 substrate and CYP2D6 substrate. Cobicistat is a strong inhibitor of CYP3A4 and an inhibitor of CYP2D6.
Codeine: (Moderate) Concomitant use of codeine with haloperidol may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of haloperidol could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If haloperidol is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Haloperidol is a moderate inhibitor of CYP2D6.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with haloperidol may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of haloperidol could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If haloperidol is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Haloperidol is a moderate inhibitor of CYP2D6.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with haloperidol may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of haloperidol could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If haloperidol is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Haloperidol is a moderate inhibitor of CYP2D6. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Codeine; Phenylephrine; Promethazine: (Moderate) Caution is advisable when combining haloperidol concurrently with promethazine as concurrent use may increase the risk of QT prolongation and other antipsychotic-related adverse effects including drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Mild to moderately increased haloperidol concentrations have also been reported when haloperidol was given concomitantly with promethazine. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, promethazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation, such as haloperidol. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the coadministered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. (Moderate) Concomitant use of codeine with haloperidol may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of haloperidol could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If haloperidol is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Haloperidol is a moderate inhibitor of CYP2D6. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Codeine; Promethazine: (Moderate) Caution is advisable when combining haloperidol concurrently with promethazine as concurrent use may increase the risk of QT prolongation and other antipsychotic-related adverse effects including drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Mild to moderately increased haloperidol concentrations have also been reported when haloperidol was given concomitantly with promethazine. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, promethazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation, such as haloperidol. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the coadministered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. (Moderate) Concomitant use of codeine with haloperidol may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of haloperidol could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If haloperidol is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Haloperidol is a moderate inhibitor of CYP2D6.
COMT inhibitors: (Major) Due to opposing effects on central dopaminergic activity, haloperidol and COMT inhibitors may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to haloperidol. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Corticosteroids: (Moderate) Caution is advisable during concurrent use of haloperidol and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with haloperidol.
Crizotinib: (Major) Avoid coadministration of crizotinib with haloperidol due to the risk of QT prolongation; haloperidol plasma concentrations may also increase. If concomitant use is unavoidable, monitor for an increase in haloperidol-related adverse reactions; also 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 is a moderate CYP3A inhibitor that has been associated with concentration-dependent QT prolongation. Haloperidol is a CYP3A4 substrate that has had reports of QT prolongation and torsade de pointes (TdP) during treatment; excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk. In clinical trials, mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with CYP3A4 inhibitors.
Cyproheptadine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Dacomitinib: (Moderate) Monitor for increased toxicity of haloperidol, such as extrapyramidal symptoms or QT prolongation, if coadministered with dacomitinib. Coadministration may increase serum concentrations of haloperidol. Haloperidol is a CYP2D6 substrate; dacomitinib is a strong CYP2D6 inhibitor.
Danazol: (Moderate) Danazol is an inhibitor of CYP3A4, one of the isoenzymes responsible for the metabolism of haloperidol. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and inhibitors of CYP3A4. Until more data are available, it is advisable to closely monitor for adverse events when these medications are co-administered.
Dantrolene: (Moderate) Simultaneous use of skeletal muscle relaxants and other CNS depressants, such as antipsychotics, can increase CNS depression.
Darifenacin: (Moderate) Haloperidol inhibits CYP2D6. Serum concentrations of darifenacin, a CYP2D6 substrate, may increase when used in combination with haloperidol. Patients should be monitored for increased anticholinergic side effects if these drugs are coadministered.
Darunavir: (Moderate) Darunavir is a substrate and inhibitor of CYP3A4, one of the isoenzymes responsible for the metabolism of haloperidol. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and substrates or inhibitors of CYP3A4. Until more data are available, it is advisable to closely monitor for adverse events when these medications are co-administered.
Darunavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with haloperidol as there is a potential for elevated haloperidol concentrations. Haloperidol is a CYP3A4 substrate and CYP2D6 substrate. Cobicistat is a strong inhibitor of CYP3A4 and an inhibitor of CYP2D6. (Moderate) Darunavir is a substrate and inhibitor of CYP3A4, one of the isoenzymes responsible for the metabolism of haloperidol. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and substrates or inhibitors of CYP3A4. Until more data are available, it is advisable to closely monitor for adverse events when these medications are co-administered.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Caution is warranted when cobicistat is administered with haloperidol as there is a potential for elevated haloperidol concentrations. Haloperidol is a CYP3A4 substrate and CYP2D6 substrate. Cobicistat is a strong inhibitor of CYP3A4 and an inhibitor of CYP2D6. (Moderate) Darunavir is a substrate and inhibitor of CYP3A4, one of the isoenzymes responsible for the metabolism of haloperidol. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and substrates or inhibitors of CYP3A4. Until more data are available, it is advisable to closely monitor for adverse events when these medications are co-administered.
Dasatinib: (Moderate) Monitor for evidence of QT prolongation and torsade de pointes (TdP) if dasatinib and haloperidol are coadministered. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. QT prolongation and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Degarelix: (Major) Avoid coadministration of degarelix with haloperidol due to the risk of reduced efficacy of degarelix; QT prolongation may also occur. Haloperidol can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; degarelix is a GnRH analog. Additionally, androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval. QT prolongation and torsade de pointes (TdP) have also been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Delavirdine: (Moderate) Delavirdine is an inhibitor of CYP2D6. Coadministration may result in decreased haloperidol metabolism and increased toxicity with concurrent use. Neurologic side effects have been noted clinically in some patients as a result of impaired haloperidol elimination.
Desflurane: (Major) QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with haloperidol include halogenated anesthetics.
Desloratadine; Pseudoephedrine: (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Desvenlafaxine: (Major) Although clinical studies have shown that desvenlafaxine does not have a clinically relevant effect on CYP2D6 inhibition at doses of 100 mg/day, the manufacturer recommends that primary substrates of CYP2D6, such as haloperidol, be dosed at the original level when co-administered with desvenlafaxine 100 mg or lower or when desvenlafaxine is discontinued. The dose of these CYP2D6 substrates should be reduced by up to one-half if co-administered with desvenlafaxine 400 mg/day.
Deutetrabenazine: (Moderate) Caution is advisable when combining haloperidol concurrently with deutetrabenazine. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and haloperidol is a dopamine antagonist. Monitor for excessive sedation and somnolence during coadministration of haloperidol and deutetrabenazine. Concurrent use may result in additive CNS depression.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Dexchlorpheniramine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Dexmedetomidine: (Moderate) Concomitant use of dexmedetomidine and haloperidol 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 intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Dextromethorphan; Bupropion: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored. In addition, bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Coadministration of bupropion with medications that are metabolized by the CYP2D6 isoenzyme, such as haloperidol, should be approached with caution. Dosage reductions of haloperidol may be needed. Conversely, if bupropion therapy is discontinued, the antipsychotic dosage may need to be increased in some patients.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as diphenhydramine, a sedating H1-blocker. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Dextromethorphan; Quinidine: (Contraindicated) Quinidine should be considered contraindicated with haloperidol. QT prolongation and torsade de pointes (TdP) have been observed during both haloperidol and quinidine treatment. Excessive doses (particularly in the overdose setting) of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval; however, quinidine is contraindicated for use with drugs that are CYP2D6 substrates that prolong the QT interval. Pretreatment with quinidine caused peak haloperidol serum concentrations and haloperidol AUC to increase.
Diazepam: (Moderate) Haloperidol can potentiate the actions of other CNS depressants, such as benzodiazepines, Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
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) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension. Diltiazem and verapamil are substrates and inhibitors of CYP3A4. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and substrates or inhibitors of CYP3A4 or CYP2D6. Elevated haloperidol concentrations occurring through inhibition of CYP2D6 or CYP3A4 may increase the risk of adverse effects, including QT prolongation.
Dimenhydrinate: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Diphenhydramine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as diphenhydramine, a sedating H1-blocker. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Diphenhydramine; Ibuprofen: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as diphenhydramine, a sedating H1-blocker. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Diphenhydramine; Naproxen: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as diphenhydramine, a sedating H1-blocker. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Diphenhydramine; Phenylephrine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as diphenhydramine, a sedating H1-blocker. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Diphenoxylate; Atropine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants, such as opiate agonists, Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Disopyramide: (Major) Haloperidol should be used cautiously and with close monitoring with disopyramide. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Dofetilide: (Major) Coadministration of dofetilide and haloperidol 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). QT prolongation and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Dolasetron: (Moderate) Administer dolasetron with caution in combination with haloperidol as concurrent use may increase the risk of QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Dolutegravir; Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with haloperidol as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Donepezil: (Moderate) Use donepezil with caution in combination with haloperidol as concurrent use may increase the risk of QT prolongation and torsade de pointes. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol and donepezil treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Donepezil; Memantine: (Moderate) Use donepezil with caution in combination with haloperidol as concurrent use may increase the risk of QT prolongation and torsade de pointes. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol and donepezil treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Dopamine: (Minor) Dopamine infusions intended to improve renal perfusion can be ineffective due to haloperidol's dopamine receptor blockade.
Dorzolamide; Timolol: (Moderate) Haloperidol should be used cautiously with timolol due to the possibility of additive hypotension.
Doxazosin: (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Doxercalciferol: (Moderate) Cytochrome P450 enzyme inhibitors, such as haloperidol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
Doxylamine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Doxylamine; Pyridoxine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Dronabinol: (Moderate) Use caution if the use of haloperidol is necessary with dronabinol, and monitor for additive dizziness, confusion, somnolence, and other CNS effects.
Dronedarone: (Contraindicated) The concomitant use of dronedarone and haloperidol is contraindicated. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. 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 1600 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.
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 haloperidol.
Duloxetine: (Moderate) Duloxetine is a moderate inhibitor of CYP2D6. Substantial increases in concentrations of antipsychotics primarily metabolized via CYP2D6, such as haloperidol may also occur. Haloperidol is associated with a possible risk of QT prolongation and should be used cautiously with CYP2D6 inhibitors such as duloxetine.
Dutasteride; Tamsulosin: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as haloperidol. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
Efavirenz: (Moderate) Consider alternatives to efavirenz when coadministering with haloperidol as concurrent use may increase the risk of QT prolongation and reduce haloperidol efficacy. Efavirenz is a moderate CYP3A4 inducer that has been associated with QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Haloperidol plasma concentration is significantly reduced when prolonged treatment (1 to 2 weeks) with enzyme-inducing drugs is added to therapy.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with haloperidol as concurrent use may increase the risk of QT prolongation and reduce haloperidol efficacy. Efavirenz is a moderate CYP3A4 inducer that has been associated with QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Haloperidol plasma concentration is significantly reduced when prolonged treatment (1 to 2 weeks) with enzyme-inducing drugs is added to therapy.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with haloperidol as concurrent use may increase the risk of QT prolongation and reduce haloperidol efficacy. Efavirenz is a moderate CYP3A4 inducer that has been associated with QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Haloperidol plasma concentration is significantly reduced when prolonged treatment (1 to 2 weeks) with enzyme-inducing drugs is added to therapy.
Elbasvir; Grazoprevir: (Moderate) Administering haloperidol with elbasvir; grazoprevir may result in elevated haloperidol plasma concentrations. Haloperidol 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: (Major) Use great caution when coadministering haloperidol and eliglustat due to the risk of serious adverse events such as QT prolongation and cardiac arrhythmias. If concurrent use is necessary, consider reducing the dosage of haloperidol and titrating to clinical effect. Although haloperidol's impact on eliglustat is unclear, it may be prudent to reduce the eliglustat dosage to 84 mg PO once daily in extensive or intermediate CYP2D6 metabolizers (EMs or IMs). If eliglustat and haloperidol are taken together, concurrent use of a strong or moderate CYP3A inhibitor should be avoided. Eliglustat is a CYP2D6 and CYP3A substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations; it is also a CYP2D6 inhibitor. Haloperidol is primarily metabolized by CYP2D6; however, its inhibitory effects are unclear. Some pharmacokinetic data suggests that haloperidol may inhibit CYP2D6 and CYP3A4, while other data suggests the risk of clinically significant inhibition is low. Regardless, haloperidol has been associated with QT prolongation and torsade de pointes (TdP). Coadministration of haloperidol and eliglustat may result in additive effects on the QT interval and, potentially, increased plasma concentrations of one or both drugs, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias).
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is warranted when cobicistat is administered with haloperidol as there is a potential for elevated haloperidol concentrations. Haloperidol is a CYP3A4 substrate and CYP2D6 substrate. Cobicistat is a strong inhibitor of CYP3A4 and an inhibitor of CYP2D6.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is warranted when cobicistat is administered with haloperidol as there is a potential for elevated haloperidol concentrations. Haloperidol is a CYP3A4 substrate and CYP2D6 substrate. Cobicistat is a strong inhibitor of CYP3A4 and an inhibitor of CYP2D6.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Caution is advised when administering rilpivirine with haloperidol as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering rilpivirine with haloperidol as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension.
Encorafenib: (Major) Avoid coadministration of encorafenib and haloperidol due to 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. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Entacapone: (Major) Due to opposing effects on central dopaminergic activity, haloperidol and COMT inhibitors may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to haloperidol. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Entrectinib: (Major) Avoid coadministration of entrectinib with haloperidol due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Enzalutamide: (Moderate) Monitor for decreased efficacy of haloperidol if coadministration with enzalutamide is necessary. Haloperidol is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased haloperidol plasma concentrations by a mean of 70% and increased mean scores on the Brief Psychiatric Rating Scale from baseline.
Epinephrine: (Major) Use of epinephrine to treat droperidol or haloperidol -induced hypotension can result in a paradoxical lowering of blood pressure due to droperidol's alpha-blocking effects. Avoid using epinephrine concurrently with droperidol and haloperidol.
Eplerenone: (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Epoprostenol: (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Eprosartan: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension. (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Eribulin: (Major) QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval, including eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
Erythromycin: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering erythromycin with haloperidol. It is prudent to use caution and carefully weighing the risks and benefits of these agents versus alternative treatment options. Erythromycin has an established risk for QT prolongation and TdP. QT prolongation and TdP have also been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) of haloperidol may be associated with a higher risk of QT prolongation. In addition, inhibition of CYP3A4 by eythromycin may result in elevated haloperidol concentrations, thereby increasing the risk of adverse effects, including QT prolongation.
Escitalopram: (Moderate) Use escitalopram with caution in combination with haloperidol as concurrent use may increase the risk of QT prolongation and haloperidol-related adverse effects. Escitalopram is a moderate CYP2D6 inhibitor that has been associated with a risk of QT prolongation and torsade de pointes (TdP). Haloperidol is a CYP2D6 substrate; QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with CYP2D6 inhi bitors.
Esketamine: (Major) Closely monitor patients receiving esketamine and haloperidol 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) Haloperidol should be used cautiously with esmolol due to the possibility of additive hypotension.
Estazolam: (Moderate) Haloperidol can potentiate the actions of other CNS depressants, such as benzodiazepines, Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Eszopiclone: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as anxiolytics, sedatives, and hypnotics, and they should be used cautiously in combination.
Ethacrynic Acid: (Moderate) Caution is advisable during concurrent use of haloperidol and loop diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension.
Ethanol: (Major) Advise patients to avoid alcohol during haloperidol treatment. Haloperidol may impair alertness, mental and/or physical abilities, and cause hypotension. These effects may be potentiated by alcohol.
Ethosuximide: (Moderate) Concomitant use of ethosuximide with haloperidol can lower the seizure threshold and reduce the effectiveness of ethosuximide as an anticonvulsant. Additive CNS effects, such as drowsiness, may also occur.
Etomidate: (Major) Haloperidol can potentiate the actions of other CNS depressants such as sedatives and hypnotics. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Fedratinib: (Moderate) Monitor for an increase in haloperidol-related adverse reactions if coadministration with fedratinib is necessary. Haloperidol is a CYP2D6 substrate and fedratinib is a moderate CYP2D6 inhibitor. In pharmacokinetic studies, mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with drugs characterized as inhibitors of CYP2D6.
Felodipine: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and haloperidol. Concurrent use may result in additive CNS depression.
Fentanyl: (Moderate) Concomitant use of fentanyl with other central nervous system (CNS) depressants, such as haloperidol, 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 haloperidol 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.
Fexofenadine; Pseudoephedrine: (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Fingolimod: (Moderate) Use haloperidol with caution in combination with fingolimod. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of torsade de pointes (TdP), such as haloperidol. 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. QT prolongation and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Flecainide: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering haloperidol with flecainide. QT prolongation and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Flecainide, a Class IC antiarrhythmic, is also associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias. In addition, flecainide is significantly metabolized by CYP2D6, and haloperidol is a CYP2D6 inhibitor. Coadministration may result in elevated flecainide serum concentrations.
Fluconazole: (Contraindicated) FDA-approved labeling for fluconazole contraindicates use with CYP3A4 substrates that prolong the QT interval such as haloperidol. If alternative therapy is not available and concurrent use cannot be avoided, closely monitor for evidence of QT prolongation; a haloperidol dose reduction may be necessary. Fluconazole is a moderate CYP3A4 inhibitor that has been associated with QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with CYP3A4 inhibitors.
Fluoxetine: (Moderate) Use fluoxetine with caution in combination with haloperidol as concurrent use may increase the risk of QT prolongation and haloperidol-related adverse effects. Fluoxetine is a strong CYP2D6 inhibitor that has been associated with a risk of QT prolongation and torsade de pointes (TdP). Haloperidol is a CYP2D6 substrate; QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with CYP2D6 inhibitors.
Fluphenazine: (Moderate) Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Haloperidol is associated with a possible risk for QT prolongation and TdP. 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.
Flurazepam: (Moderate) Haloperidol can potentiate the actions of other CNS depressants, such as benzodiazepines, Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Fluvoxamine: (Moderate) Use fluvoxamine with caution in combination with haloperidol as concurrent use may increase the risk of QT prolongation and haloperidol-related adverse effects. Fluvoxamine is a moderate CYP3A4 inhibitor that has been associated with a risk of QT prolongation and torsade de pointes (TdP). Haloperidol is a CYP3A4 substrate; QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with CYP3A4 inhibitors.
Fosamprenavir: (Moderate) Fosamprenavir is an inhibitor of CYP3A4. CYP3A4 is one of the isoenzymes responsible for the metabolism of haloperidol. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and inhibitors of CYP3A4. Elevated haloperidol concentrations occurring through inhibition of CYP3A4 may increase the risk of adverse effects, including QT prolongation. Until more data are available, it is advisable to closely monitor for adverse events when these medications are co-administered.
Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as haloperidol. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). QT prolongation and TdP have also been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension.
Fostemsavir: (Moderate) Caution is advised when combining haloperidol concurrently with fostemsavir. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. 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) Caution is advisable during concurrent use of haloperidol and loop diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension.
Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and haloperidol. Concomitant use of gabapentin with haloperidol may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
Ganirelix: (Moderate) In the absence of relevant data and as a precaution, drugs that cause hyperprolactinemia, such as antipsychotics, should not be administered concomitantly with gonadotropin releasing hormone analogs since hyperprolactinemia downregulates the number of pituitary GnRH receptors.
Gemifloxacin: (Moderate) Use haloperidol with caution in combination with gemifloxacin as concurrent use may increase the risk of QT prolongation. QT prolongation and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Gemifloxacin may also 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 haloperidol 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. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Gilteritinib: (Moderate) Use caution and monitor for evidence of QT prolongation if concurrent use of gilteritinib and haloperidol is necessary. Gilteritinib has been associated with QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Glasdegib: (Major) Avoid coadministration of glasdegib with haloperidol due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Glycerol Phenylbutyrate: (Moderate) Haloperidol may induce elevated blood ammonia concentrations. Use caution and monitor ammonia concentrations closely if co-administration of haloperidol and glycerol phenylbutyrate is necessary.
Glycopyrrolate: (Moderate) Coadministration of glycopyrrolate with haloperidol may decrease haloperidol serum concentrations, which may lead to worsening of psychiatric symptoms and the development of tardive dyskinesia. If coadministration is necessary, closely monitor patient.
Glycopyrrolate; Formoterol: (Moderate) Coadministration of glycopyrrolate with haloperidol may decrease haloperidol serum concentrations, which may lead to worsening of psychiatric symptoms and the development of tardive dyskinesia. If coadministration is necessary, closely monitor patient.
Goserelin: (Major) Avoid coadministration of goserelin with haloperidol due to the risk of reduced efficacy of goserelin; QT prolongation may also occur. Haloperidol can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; goserelin is a GnRH analog. Additionally, QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment; excessive doses (particularly in the overdose setting) or IV administration may be associated with a higher risk. Androgen deprivation therapy (i.e., goserelin) may prolong the QT/QTc interval.
Granisetron: (Moderate) Caution is advisable when combining haloperidol concurrently with haloperidol as concurrent use may increase the risk of QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Granisetron has been associated with QT prolongation.
Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with haloperidol may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of haloperidol could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If haloperidol is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Haloperidol is a moderate inhibitor of CYP2D6.
Guaifenesin; Phenylephrine: (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Guaifenesin; Pseudoephedrine: (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Guanfacine: (Moderate) Disturbances of orthostatic regulation (e.g., orthostatic hypotension, dizziness, fatigue) and additive sedation may occur in patients receiving concomitant clonidine and antipsychotics. Also, based on observations in patients in a state of alcoholic delirium, high intravenous doses of clonidine may increase the arrhythmogenic potential (QT prolongation, ventricular fibrillation) of high intravenous doses of haloperidol. A causal relationship and relevance for clonidine oral tablets have not been established.
Halogenated Anesthetics: (Major) QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with haloperidol include halogenated anesthetics.
Histrelin: (Major) Avoid coadministration of histrelin with haloperidol due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Haloperidol can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Additionally, QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment; excessive doses (particularly in the overdose setting) or IV administration may be associated with a higher risk. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval.
Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with haloperidol may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of haloperidol could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If haloperidol is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Haloperidol is a moderate inhibitor of CYP2D6.
Hydantoins: (Major) Haloperidol is metabolized in the liver; hydantoin anticonvulsants are known to induce certain hepatic enzymes. Clinicians should monitor for reduced haloperidol effectiveness if a hydantoin is used concurrently. Conversely, the discontinuation of these drugs may produce an increase in haloperidol concentrations. Additionally, antipsychotic use may lower the seizure threshold in patients receiving anticonvulsants, although the risk is less with haloperidol than with the phenothiazines. Additional CNS depression may occur when haloperidol is given with anticonvulsant drugs.
Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension.
Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension. (Moderate) Disturbances of orthostatic regulation (e.g., orthostatic hypotension, dizziness, fatigue) and additive sedation may occur in patients receiving concomitant clonidine and antipsychotics. Also, based on observations in patients in a state of alcoholic delirium, high intravenous doses of clonidine may increase the arrhythmogenic potential (QT prolongation, ventricular fibrillation) of high intravenous doses of haloperidol. A causal relationship and relevance for clonidine oral tablets have not been established.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension.
Hydrocodone: (Moderate) Concomitant use of hydrocodone with haloperidol may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of haloperidol could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If haloperidol is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Haloperidol is a moderate inhibitor of CYP2D6.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with haloperidol may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of haloperidol could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If haloperidol is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Haloperidol is a moderate inhibitor of CYP2D6.
Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with haloperidol may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of haloperidol could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If haloperidol is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Haloperidol is a moderate inhibitor of CYP2D6. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
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 haloperidol. 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) Avoid coadministration of haloperidol and hydroxychloroquine due to the risk of increased 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. Hydroxychloroquine prolongs the QT interval. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Hydroxyzine: (Moderate) Concomitant use of hydroxyzine and haloperidol 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 intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Hyoscyamine: (Moderate) Additive adverse effects resulting from cholinergic blockade may occur when hyoscyamine is administered concomitantly with haloperidol.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Additive adverse effects resulting from cholinergic blockade may occur when hyoscyamine is administered concomitantly with haloperidol.
Ibuprofen; Oxycodone: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as opiate agonists. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Ibuprofen; Pseudoephedrine: (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Ibutilide: (Major) QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval. 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.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with haloperidol, a CYP3A substrate, as haloperidol toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Iloperidone: (Major) Haloperidol should be avoided in combination with iloperidone, due to duplicative antipsychotic effects and the potential for additive effects on the QT interval. Haloperidol is associated with a possible risk for QT prolongation and torsade de pointes (TdP) and iloperidone has been associated with QT prolongation. Coadministration 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.
Iloprost: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Imatinib: (Moderate) Imatinib, STI-571 is an inhibitor of CYP2D6 and CYP3A4, the isoenzymes responsible for the metabolism of haloperidol. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and inhibitors of CYP3A4 or CYP2D6. Until more data are available, it is advisable to closely monitor for adverse events when these medications are co-administered.
Indacaterol; Glycopyrrolate: (Moderate) Coadministration of glycopyrrolate with haloperidol may decrease haloperidol serum concentrations, which may lead to worsening of psychiatric symptoms and the development of tardive dyskinesia. If coadministration is necessary, closely monitor patient.
Indinavir: (Moderate) Indinavir is a substrate and inhibitor of CYP3A4, one of the isoenzymes responsible for the metabolism of haloperidol. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and substrates or inhibitors of CYP3A4. Until more data are available, it is advisable to closely monitor for adverse events when these medications are co-administered.
Indocyanine Green: (Moderate) Haloperidol may increase the clearance of indocyanine green. The half-life of indocyanine green was lower in patients taking the drugs concomitantly compared to patients with normal and abnormal liver function taking no concomitant medications. The mechanism of interaction is unclear; those proposed in the medical literature include increased indocyanine green uptake by the liver cell, enhanced binding by specific hepatic carrier proteins, or more rapid excretion into bile.
Indomethacin: (Minor) In a small study, during concomitant administration of haloperidol with indomethacin, adverse reactions, such as drowsiness and other effects, to haloperidol appeared to be intensified. Although more data are needed to confirm these findings, clinicians should administer indomethacin to patients stabilized on haloperidol cautiously. The effect of other NSAIDs on haloperidol are unknown.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with haloperidol due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. QT prolongation and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Irbesartan: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension. (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with haloperidol may result in increased serum concentrations of haloperidol. Haloperidol is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Isoflurane: (Major) QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with haloperidol include halogenated anesthetics.
Isoniazid, INH: (Moderate) Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and inhibitors of CYP3A4, such as isoniazid. Elevated haloperidol concentrations occurring through inhibition of CYP3A4 may increase the risk of adverse effects, including QT prolongation. Monitor for adverse events when these medications are coadministered.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Limited data suggest that rifampin, a potent CYP inducer, can increase the metabolism and/or reduce the bioavailability of haloperidol. In one small study (n=12), plasma levels of haloperidol were decreased by a mean of 70% and mean scores on the Brief Psychiatric Rating Scale (BPRS) were increased from baseline during concurrent use of rifampin. Discontinuation of rifampin has resulted in a mean 3.3-fold increase in haloperidol concentrations in some instances. Haloperidol dosage adjustments should be made as needed when rifampin is added or discontinued. Prolonged use of CYP inducers such as rifampin in patients receiving haloperidol has resulted in significant reductions in haloperidol plasma concentrations. (Moderate) Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and inhibitors of CYP3A4, such as isoniazid. Elevated haloperidol concentrations occurring through inhibition of CYP3A4 may increase the risk of adverse effects, including QT prolongation. Monitor for adverse events when these medications are coadministered.
Isoniazid, INH; Rifampin: (Major) Limited data suggest that rifampin, a potent CYP inducer, can increase the metabolism and/or reduce the bioavailability of haloperidol. In one small study (n=12), plasma levels of haloperidol were decreased by a mean of 70% and mean scores on the Brief Psychiatric Rating Scale (BPRS) were increased from baseline during concurrent use of rifampin. Discontinuation of rifampin has resulted in a mean 3.3-fold increase in haloperidol concentrations in some instances. Haloperidol dosage adjustments should be made as needed when rifampin is added or discontinued. Prolonged use of CYP inducers such as rifampin in patients receiving haloperidol has resulted in significant reductions in haloperidol plasma concentrations. (Moderate) Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and inhibitors of CYP3A4, such as isoniazid. Elevated haloperidol concentrations occurring through inhibition of CYP3A4 may increase the risk of adverse effects, including QT prolongation. Monitor for adverse events when these medications are coadministered.
Isradipine: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Itraconazole: (Moderate) Use itraconazole with caution in combination with haloperidol as concurrent use may increase the risk of QT prolongation and haloperidol-related adverse effects. A haloperidol dose reduction may be necessary. Itraconazole is a strong CYP3A4 inhibitor that has been associated with prolongation of the QT interval. Haloperidol is a CYP3A4 substrate; QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with CYP3A4 inhibitors.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with haloperidol due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Ketamine: (Major) Haloperidol can potentiate the actions of other CNS depressants such as general anesthetics. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and haloperidol due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. The intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration. Additionally, concomitant use may increase the exposure of haloperidol, further increasing the risk for adverse effects. Haloperidol is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor.
Labetalol: (Moderate) Haloperidol should be used cautiously with labetalol due to the possibility of additive hypotension.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Concurrent use of clarithromycin and haloperidol should be avoided if possible. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval. Because clarithromycin is also associated with an increased risk for QT prolongation and TdP, the need to coadminister clarithromycin with drugs known to prolong the QT interval should be done with a careful assessment of risks versus benefits. Clarithromycin is an inhibitor of CYP3A4. Elevated haloperidol concentrations occurring through inhibition of CYP3A4 or CYP2D6 may increase the risk of adverse effects, including QT prolongation.
Lapatinib: (Moderate) Monitor for evidence of QT prolongation and an increase in haloperidol-related adverse reactions if administered with lapatinib. Haloperidol is a CYP3A4 substrate that has been associated QT prolongation and torsade de pointes (TdP) during treatment; excessive doses (particularly in the overdose setting) or IV administration may be associated with a higher risk. Lapatinib is a weak CYP3A4 inhibitor that has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and TdP have been reported in postmarketing experience with lapatinib. In clinical trials, mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with CYP3A4 inhibitors.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and haloperidol. Concurrent use may result in additive CNS depression.
Lefamulin: (Major) Avoid coadministration of lefamulin with haloperidol 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. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with haloperidol due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. QT prolongation and torsade de pointes (TdP) have also been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Letermovir: (Moderate) A clinically relevant increase in the plasma concentration of haloperidol may occur if given with letermovir. Haloperidol dose reductions may be needed in patients also receiving cyclosporine, because the magnitude of the interaction may be increased. Haloperidol is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates is similar to a strong CYP3A4 inhibitor. In a drug interaction study, administration with another strong CYP3A4 inhibitor resulted in QT prolongation.
Leuprolide: (Major) Avoid coadministration of leuprolide with haloperidol due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Haloperidol can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Additionally, QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment; excessive doses (particularly in the overdose setting) or IV administration may be associated with a higher risk. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Leuprolide; Norethindrone: (Major) Avoid coadministration of leuprolide with haloperidol due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Haloperidol can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Additionally, QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment; excessive doses (particularly in the overdose setting) or IV administration may be associated with a higher risk. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Levamlodipine: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with haloperidol should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Levodopa: (Major) Due to opposing effects on central dopaminergic activity, haloperidol and levodopa may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to haloperidol. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Levofloxacin: (Moderate) Concomitant use of levofloxacin and haloperidol 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 intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and haloperidol due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. The intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration. Additionally, concomitant use may increase the exposure of haloperidol, further increasing the risk for adverse effects. Haloperidol is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor.
Levorphanol: (Moderate) Concomitant use of levorphanol with other CNS depressants such as haloperidol 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) Use of epinephrine to treat droperidol or haloperidol -induced hypotension can result in a paradoxical lowering of blood pressure due to droperidol's alpha-blocking effects. Avoid using epinephrine concurrently with droperidol and haloperidol.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension.
Lithium: (Moderate) Use lithium with caution in combination with haloperidol as concurrent use may increase the risk of QT prolongation, neuroleptic malignant syndrome (NMS), and extrapyramidal effects. Both drugs have been associated with QT prolongation. Torsade de pointes (TdP) has been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. NMS has been observed occasionally during concurrent use of lithium and either atypical or conventional antipsychotics. Early case reports described an encephalopathic syndrome consisting of delirium, tremulousness, dyskinesia, seizures, leukocytosis, weakness, hyperpyrexia, confusion, extrapyramidal symptoms, elevations in laboratory values (e.g., liver function tests, blood urea nitrogen, fasting blood sugar) and, in some cases, irreversible brain damage, during use of lithium and conventional antipsychotics, particularly haloperidol. Subsequent rare reports of NMS or NMS-like reactions have been described during co-administration of lithium and atypical antipsychotics (e.g., risperidone, olanzapine, clozapine). Following resolution of NMS, there are isolated instances of re-emergence of symptoms following re-initiation of lithium as monotherapy. Lithium may be a risk factor for antipsychotic-induced NMS; however, this hypothesis has not been confirmed. In many reported cases, confounding factors have been present (e.g., previous history of NMS, high dose therapy). The ability of antipsychotics alone to precipitate NMS and the rarity of the condition further complicate assessment of lithium as a risk factor.
Lofexidine: (Major) Monitor ECG for QT prolongation during concurrent use of lofexidine and haloperidol. Lofexidine may prolong the QT interval, torsade de pointes (TdP) has been reported during postmarketing use. Haloperidol is associated with an established risk of QT prolongation and TdP. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Lonafarnib: (Moderate) Monitor for an increase in haloperidol-related side effects, such as QT prolongation and extrapyramidal symptoms, if coadministered with lonafarnib. Coadministration may increase the exposure of haloperidol. Haloperidol is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor.
Loop diuretics: (Moderate) Caution is advisable during concurrent use of haloperidol and loop diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension.
Loperamide: (Moderate) Concomitant use of loperamide and haloperidol may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Loperamide; Simethicone: (Moderate) Concomitant use of loperamide and haloperidol may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with haloperidol 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. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. (Moderate) Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and inhibitors of CYP3A4 or CYP2D6, such as ritonavir. Elevated haloperidol concentrations may increase the risk of adverse effects. Closely monitor for adverse events when these medications are coadministered.
Loratadine; Pseudoephedrine: (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Lorazepam: (Moderate) Haloperidol can potentiate the actions of other CNS depressants, such as benzodiazepines, Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Losartan: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension. (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Loxapine: (Major) Caution is advisable during concurrent use of loxapine and other antipsychotics. 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 other antipsychotics. 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.
Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may decrease the systemic exposure and therapeutic efficacy of haloperidol with prolonged (1 to 2 weeks) coadministration. Carefully monitor clinical status when lumacaftor; ivacaftor is administered or discontinued in haloperidol-treated patients. Haloperidol may require dosage adjustment to achieve the desired clinical response. If lumacaftor; ivacaftor is subsequently discontinued, it may be necessary to reduce the haloperidol dosage. Haloperidol is a CYP3A substrate. Lumacaftor is a strong CYP3A inducer. Coadministration of haloperidol and rifampin, another strong CYP3A inducer, resulted in a 70% decrease in haloperidol plasma concentrations in 12 schizophrenic patients; correspondingly, Brief Psychiatric Rating Scale scores increased from baseline. In 5 other schizophrenic patients also treated with haloperidol and rifampin, antibiotic discontinuation resulted in a 3.3-fold increase in haloperidol concentrations.
Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may decrease the systemic exposure and therapeutic efficacy of haloperidol with prolonged (1 to 2 weeks) coadministration. Carefully monitor clinical status when lumacaftor; ivacaftor is administered or discontinued in haloperidol-treated patients. Haloperidol may require dosage adjustment to achieve the desired clinical response. If lumacaftor; ivacaftor is subsequently discontinued, it may be necessary to reduce the haloperidol dosage. Haloperidol is a CYP3A substrate. Lumacaftor is a strong CYP3A inducer. Coadministration of haloperidol and rifampin, another strong CYP3A inducer, resulted in a 70% decrease in haloperidol plasma concentrations in 12 schizophrenic patients; correspondingly, Brief Psychiatric Rating Scale scores increased from baseline. In 5 other schizophrenic patients also treated with haloperidol and rifampin, antibiotic discontinuation resulted in a 3.3-fold increase in haloperidol concentrations.
Lumateperone: (Moderate) Coadministration of antipsychotics, such as lumateperone and haloperidol, 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: (Major) Similar to other antipsychotics, lurasidone administration has been associated with drowsiness, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. The risk of these adverse effects may be increased during concurrent use of lurasidone with other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent (see separate drug monographs). 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 haloperidol. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Maprotiline: (Major) Haloperidol can potentiate the actions of other CNS depressants such as cyclic antidepressants. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects. Limited data suggest that haloperidol may inhibit the metabolism of some tricyclic antidepressants, however, the clinical significance of this interaction and the effect on maprotiline is uncertain. Haloperidol is an inhibitor of hepatic CYP2D6, and coadministration with maprotiline (CYP2D6 substrate) may lead to elevated maprotiline serum concentrations, potentiating toxicity. Haloperidol has also been associated with a possible risk for QT prolongation and/or torsades de pointes, particularly when excessive doses are used or in overdose. Haloperidol should be used cautiously with other agents that may have this effect (e.g., maprotiline).
Mecamylamine: (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Meclizine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Mefloquine: (Moderate) Mefloquine should be used with caution in patients receiving haloperidol as concurrent use may increase the risk of QT prolongation. 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. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Meperidine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as opiate agonists. Dose reduction of one or both drugs is necessary.
Meprobamate: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as anxiolytics, sedatives, and hypnotics, and they should be used cautiously in combination.
Methadone: (Major) The need to coadminister methadone with drugs known to prolong the QT interval should be done with extreme caution and a careful assessment of treatment risks versus benefits. Methadone is considered to be associated with an increased risk for QT prolongation and torsades de pointes (TdP), especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). In addition, methadone is a substrate for CYP3A4, CYP2D6, and P-glycoprotein (P-gp). Concurrent use of methadone with inhibitors of these enzymes may result in increased serum concentrations of methadone. Drugs with a possible risk for QT prolongation and TdP that inhibit CYP2D6 include haloperidol. Concomitant use of methadone with another CNS depressant, such as haloperidol, can also lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of methadone 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. Methadone should be used with caution and in reduced dosages if used concurrently with a CNS depressant; in opioid-naive adults, use an initial methadone dose of 2.5 mg every 12 hours. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
Methazolamide: (Moderate) Caution is advisable during concurrent use of haloperidol and methazolamide as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Additive adverse effects resulting from cholinergic blockade may occur when hyoscyamine is administered concomitantly with haloperidol.
Methohexital: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as barbiturates. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Methyclothiazide: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension.
Methyldopa: (Moderate) Disturbances of orthostatic regulation (e.g., orthostatic hypotension, dizziness, fatigue) and additive sedation may occur in patients receiving concomitant clonidine and antipsychotics. Also, based on observations in patients in a state of alcoholic delirium, high intravenous doses of clonidine may increase the arrhythmogenic potential (QT prolongation, ventricular fibrillation) of high intravenous doses of haloperidol. A causal relationship and relevance for clonidine oral tablets have not been established.
Metoclopramide: (Contraindicated) Avoid metoclopramide in patients receiving haloperidol. 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.
Metolazone: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension.
Metoprolol: (Moderate) Monitor for increased metoprolol adverse reactions including bradycardia and hypotension during coadministration. A dosage reduction for metoprolol may be needed based on response. Concurrent use may increase metoprolol exposure. Metoprolol is a CYP2D6 substrate; haloperidol is a moderate CYP2D6 inhibitor. In the presence of another moderate CYP2D6 inhibitor, the AUC of metoprolol was increased by 3.29-fold with no effect on the cardiovascular response to metoprolol.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension. (Moderate) Monitor for increased metoprolol adverse reactions including bradycardia and hypotension during coadministration. A dosage reduction for metoprolol may be needed based on response. Concurrent use may increase metoprolol exposure. Metoprolol is a CYP2D6 substrate; haloperidol is a moderate CYP2D6 inhibitor. In the presence of another moderate CYP2D6 inhibitor, the AUC of metoprolol was increased by 3.29-fold with no effect on the cardiovascular response to metoprolol.
Metronidazole: (Moderate) Concomitant use of metronidazole and haloperidol 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 intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Metyrapone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as haloperidol, should be used with caution. Additive drowsiness and/or dizziness is possible.
Metyrosine: (Moderate) The extrapyramidal effects of haloperidol can be increased by concomitant administration of metyrosine.
Mexiletine: (Moderate) Mexiletine is significantly metabolized by CYP2D6 isoenzymes. CYP2D6 inhibitors, such as haloperidol, could theoretically impair mexiletine metabolism; the clinical significance of such interactions is unknown.
Midazolam: (Moderate) Haloperidol can potentiate the actions of other CNS depressants, such as benzodiazepines, Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Midostaurin: (Major) The concomitant use of midostaurin and haloperidol may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram 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. QT prolongation and torsade de pointes have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Mifepristone: (Major) Avoid use together if possible due to an additive risk for QT prolongation and elevated haloperidol concentrations, which may lead to drug-related adverse events. Consider alternatives to haloperidol if possible. If use together is necessary, some patients may require haloperidol dose reduction; closely monitor for adverse events. Mifepristone inhibits CYP3A4 and has been associated with QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Mild to moderate increases in haloperidol exposure have been reported during concurrent use with inhibitors of CYP3A4.
Mirabegron: (Moderate) Mirabegron is a substrate and a moderate inhibitor of CYP2D6. Exposure of drugs metabolized by CYP2D6 such as haloperidol may be increased when co-administered with mirabegron. Haloperidol is primarily metabolized by CYP2D6. In addition, in vitro data suggest that haloperidol has CYP2D6 inhibitory effects and has the potential to decrease the metabolism of CYP2D6 substrates such as mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Mirtazapine: (Moderate) Concomitant use of mirtazapine and haloperidol 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 intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Mitotane: (Major) Use caution if mitotane and haloperidol are used concomitantly, and monitor for decreased efficacy of haloperidol and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and haloperidol is a CYP3A4 substrate in vitro; coadministration may result in decreased plasma concentrations of haloperidol. Limited data suggest that rifampin, another potent CYP inducer, can increase the metabolism and/or reduce the bioavailability of haloperidol. In one small study (n=12), plasma levels of haloperidol were decreased by a mean of 70% and mean scores on the Brief Psychiatric Rating Scale (BPRS) were increased from baseline during concurrent use of rifampin; discontinuation of rifampin resulted in a mean 3.3-fold increase in haloperidol concentrations in some instances. In another study (n = 11), patients who received increasing doses of carbamazepine had decreasing haloperidol plasma concentrations in linear proportion to the increasing carbamazepine concentrations. Careful monitoring of clinical status is warranted when CYP3A enzyme inducing drugs are administered or discontinued in haloperidol-treated patients. Additionally, mitotane can cause sedation, lethargy, vertigo, and other CNS adverse reactions; additive CNS effects may occur initially when mitotane is given concurrently with haloperidol.
Mobocertinib: (Major) Concomitant use of mobocertinib and haloperidol 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. The intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Molindone: (Major) Close monitoring is advisable during concurrent use of molindone with other antipsychotics. Because molindone shares certain pharmacological properties with other antipsychotics, additive cardiac effects (e.g., hypotension), CNS effects (e.g., drowsiness), or anticholinergic effects (e.g., constipation, xerostomia) may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
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 haloperidol. 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 haloperidol. 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: (Major) Concurrent use of haloperidol and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). 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. QT prolongation and TdP have also been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Nabilone: (Moderate) Concomitant use of nabilone with other CNS depressants can potentiate the effects of nabilone on respiratory depression.
Nadolol: (Moderate) Haloperidol should be used cautiously with nadolol due to the possibility of additive hypotension.
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) Concomitant use of nalbuphine with other CNS depressants, such as haloperidol, can potentiate the effects of nalbuphine on respiratory depression, CNS depression, and sedation.
Naproxen; Pseudoephedrine: (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Nebivolol: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with haloperidol. Nebivolol is metabolized by CYP2D6. Although data are lacking, significant CYP2D6 inhibitors, such as haloperidol, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible.
Nebivolol; Valsartan: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension. (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with haloperidol. Nebivolol is metabolized by CYP2D6. Although data are lacking, significant CYP2D6 inhibitors, such as haloperidol, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible.
Nefazodone: (Moderate) Nefazodone is an inhibitor of CYP3A4, one of the isoenzymes responsible for the metabolism of haloperidol. In one study, concurrent use of nefazodone and haloperidol resulted in a 36%, 13%, and 37% increase in mean AUC, highest concentration, and 12-h concentration values for haloperidol, respectively; however, only the increase in AUC was statistically significant. Elevated haloperidol concentrations occurring through inhibition of CYP3A4 may increase the risk of adverse effects, including QT prolongation or additive CNS effects. A lower doses of haloperidol may be required in some patients receiving this combination.
Nelfinavir: (Moderate) Nelfinavir is a substrate and inhibitor of CYP3A4, one of the isoenzymes responsible for the metabolism of haloperidol. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and substrates or inhibitors of CYP3A4. Until more data are available, it is advisable to closely monitor for adverse events when these medications are co-administered.
Neostigmine; Glycopyrrolate: (Moderate) Coadministration of glycopyrrolate with haloperidol may decrease haloperidol serum concentrations, which may lead to worsening of psychiatric symptoms and the development of tardive dyskinesia. If coadministration is necessary, closely monitor patient.
Nicardipine: (Major) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension. In addition, nicardipine is an inhibitor of CYP2D6 and CYP3A4, the isoenzymes responsible for the metabolism of haloperidol. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and substrates or inhibitors of CYP3A4 or CYP2D6. Elevated haloperidol concentrations occurring through inhibition of cytochrome P450 pathways may increase the risk of adverse effects, including QT prolongation. Until more data are available, it is advisable to closely monitor for adverse events when these medications are co-administered.
Nifedipine: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Nilotinib: (Major) Avoid administration of nilotinib with other drugs with a known potential to prolong the QT interval, such as haloperidol. Sudden death and QT interval prolongation have occurred in patients who received nilotinib therapy. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Niraparib; Abiraterone: (Moderate) Monitor for an increase in haloperidol-related adverse reactions if coadministration with abiraterone is necessary. Haloperidol is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. In pharmacokinetic studies, mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with drugs characterized as inhibitors of CYP2D6.
Nirmatrelvir; Ritonavir: (Moderate) Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and inhibitors of CYP3A4 or CYP2D6, such as ritonavir. Elevated haloperidol concentrations may increase the risk of adverse effects. Closely monitor for adverse events when these medications are coadministered.
Nisoldipine: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Non-Ionic Contrast Media: (Major) Haloperidol lowers the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ofloxacin: (Moderate) Concomitant use of ofloxacin and haloperidol 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 intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Olanzapine: (Moderate) Caution is advised when administering olanzapine with haloperidol as concurrent use may increase the risk of QT prolongation; additive antipsychotic-related adverse effects (e.g., drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures) may also occur. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. The likelihood of additive pharmacodynamic interactions varies based upon the individual properties of the coadministered 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.
Olanzapine; Fluoxetine: (Moderate) Caution is advised when administering olanzapine with haloperidol as concurrent use may increase the risk of QT prolongation; additive antipsychotic-related adverse effects (e.g., drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures) may also occur. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. The likelihood of additive pharmacodynamic interactions varies based upon the individual properties of the coadministered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. (Moderate) Use fluoxetine with caution in combination with haloperidol as concurrent use may increase the risk of QT prolongation and haloperidol-related adverse effects. Fluoxetine is a strong CYP2D6 inhibitor that has been associated with a risk of QT prolongation and torsade de pointes (TdP). Haloperidol is a CYP2D6 substrate; QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with CYP2D6 inhibitors.
Olanzapine; Samidorphan: (Moderate) Caution is advised when administering olanzapine with haloperidol as concurrent use may increase the risk of QT prolongation; additive antipsychotic-related adverse effects (e.g., drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures) may also occur. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. The likelihood of additive pharmacodynamic interactions varies based upon the individual properties of the coadministered 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.
Oliceridine: (Major) Concomitant use of oliceridine with haloperidol may cause excessive sedation and somnolence. Limit the use of oliceridine with haloperidol 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: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension. (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension. (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension. (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Omeprazole; Amoxicillin; Rifabutin: (Major) Significant reductions in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and CYP3A4 enzyme-inducing drugs such as carbamazepine or rifampin. Rifabutin is an inducer and a substrate of CYP3A4. Haloperidol dosage adjustments should be made as needed when rifabutin is added or discontinued.
Ondansetron: (Major) Concomitant use of ondansetron and haloperidol 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. The intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Opicapone: (Major) Due to opposing effects on central dopaminergic activity, haloperidol and COMT inhibitors may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to haloperidol. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Oritavancin: (Moderate) Haloperidol is metabolized by CYP3A4 and CYP2D6; oritavancin is a weak CYP3A4 and CYP2D6 inducer. Plasma concentrations and efficacy of haloperidol may be reduced if these drugs are administered concurrently.
Orphenadrine: (Moderate) Orphenadrine has mild anticholinergic activity. Concomitant use of orphenadrine and haloperidol may worsen schizophrenic symptoms. Tardive dyskinesia may also develop.
Osilodrostat: (Moderate) Monitor ECGs in patients receiving osilodrostat with haloperidol. Osilodrostat is associated with dose-dependent QT prolongation. QT prolongation and torsade de pointes have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Osimertinib: (Major) Avoid coadministration of haloperidol with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, 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. QT prolongation and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of haloperidol with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
Oxazepam: (Moderate) Haloperidol can potentiate the actions of other CNS depressants, such as benzodiazepines, Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Oxcarbazepine: (Moderate) Careful monitoring of clinical status is warranted when oxcarbazepine, an enzyme-inducing drug, is administered or discontinued in haloperidol-treated patients. Adjust the haloperidol dose as clinically necessary. After discontinuation of oxcarbazepine, it may be necessary to reduce the haloperidol dosage. Significant reductions in haloperidol plasma concentrations have been reported during concurrent use of CYP3A4 enzyme-inducing drugs. Because antipsychotics such as haloperidol may lower the seizure threshold, a reduction in anticonvulsant efficacy may also occur if oxcarbazepine is used for seizures. Additive CNS effects, such as sedation, may also occur in some patients.
Oxycodone: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as opiate agonists. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
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 haloperidol. 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 haloperidol due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. QT prolongation and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Pacritinib: (Major) Concomitant use of pacritinib and haloperidol 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. The intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Palbociclib: (Moderate) Monitor for an increase in haloperidol-related adverse reactions if coadministration with palbociclib is necessary. Haloperidol is a CYP3A4 substrate and palbociclib is a weak, time-dependent CYP3A4 inhibitor. In clinical trials, mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with CYP3A4 inhibitors.
Paliperidone: (Major) Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer of paliperidone, the drug should be avoided in combination with other agents also known to have this effect, such as haloperidol. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. If coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential. In addition, coadministration of two antipsychotics may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Panobinostat: (Major) The co-administration of panobinostat with haloperidol is not recommended; QT prolongation has been reported with both agents. If concomitant use cannot be avoided, closely monitor patients for signs and symptoms of haloperidol toxicity, including QT prolongation and cardiac arrhythmias. Panobinostat is a CYP2D6 inhibitor and haloperidol is a CYP2D6 substrate. When a single-dose of a CYP2D6-sensitive substrate was administered after 3 doses of panobinostat (20 mg given on days 3, 5, and 8), the CYP2D6 substrate Cmax increased by 20% to 200% and the AUC value increased by 20% to 130% in 14 patients with advanced cancer; exposure was highly variable (coefficient of variance > 150%).
Paroxetine: (Moderate) Monitor for an increase in haloperidol- and paroxetine-related side effects, such as QT prolongation, extrapyramidal symptoms, and serotonin syndrome, if coadministration is necessary. Coadministration may increase the exposure of both drugs. Both drugs are CYP2D6 substrates; paroxetine is a strong CYP2D6 inhibitor and haloperidol is a CYP2D6 inhibitor.
Pasireotide: (Moderate) Use caution when using pasireotide in combination with haloperidol as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. If pazopanib and haloperidol must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and haloperidol, a CYP3A4 substrate, may cause an increase in systemic concentrations of haloperidol. Use caution when concurrent administration of haloperidol and pazopanib is necessary.
Peginterferon Alfa-2b: (Moderate) Monitor for adverse effects associated with increased exposure to haloperidol if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while haloperidol is a CYP2D6 substrate.
Pentamidine: (Major) QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval, including pentamidine.
Pentazocine: (Moderate) Concomitant use of pentazocine with other CNS depressants can potentiate respiratory depression, CNS depression, and sedation. Pentazocine should be used cautiously in any patient receiving these agents, which may include haloperidol.
Pentazocine; Naloxone: (Moderate) Concomitant use of pentazocine with other CNS depressants can potentiate respiratory depression, CNS depression, and sedation. Pentazocine should be used cautiously in any patient receiving these agents, which may include haloperidol.
Pentobarbital: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as barbiturates. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
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 haloperidol.
Perindopril; Amlodipine: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Perphenazine: (Moderate) Caution is advisable when combining haloperidol concurrently with perphenazine as concurrent use may increase the risk of QT prolongation and other antipsychotic-related adverse effects including drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation, such as haloperidol. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the coadministered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Perphenazine; Amitriptyline: (Moderate) Caution is advisable when combining haloperidol concurrently with perphenazine as concurrent use may increase the risk of QT prolongation and other antipsychotic-related adverse effects including drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation, such as haloperidol. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the coadministered 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.
Phenobarbital: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as barbiturates. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Additive adverse effects resulting from cholinergic blockade may occur when hyoscyamine is administered concomitantly with haloperidol. (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as barbiturates. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Phenoxybenzamine: (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Phenylephrine: (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as haloperidol. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Coadministration may increase the risk for QT prolongation.
Pimozide: (Contraindicated) Haloperidol has a risk of QT prolongation and is contraindicated with pimozide. Concurrent use of pimozide with haloperidol 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. Haloperidol is an inhibitor of CYP2D6, one of the metabolic pathways of pimozide.
Pindolol: (Moderate) Haloperidol should be used cautiously with pindolol due to the possibility of additive hypotension.
Pitolisant: (Major) Avoid coadministration of pitolisant with haloperidol as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking haloperidol due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. QT prolongation and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Posaconazole: (Contraindicated) FDA-approved labeling for posaconazole contraindicates coadministration with CYP3A4 substrates that also cause QT prolongation such as haloperidol. If alternative therapy is not available and concurrent use cannot be avoided, closely monitor for evidence of QT prolongation; a haloperidol dose reduction may be necessary. Posaconazole is a strong CYP3A4 inhibitor that has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with CYP3A4 inhibitors.
Potassium-sparing diuretics: (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Pramipexole: (Major) Due to opposing effects on central dopaminergic activity, haloperidol and pramipexole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to haloperidol. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Additive sedation is also possible.
Prazosin: (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and haloperidol. Concomitant use of pregabalin with haloperidol may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
Prilocaine; Epinephrine: (Major) Use of epinephrine to treat droperidol or haloperidol -induced hypotension can result in a paradoxical lowering of blood pressure due to droperidol's alpha-blocking effects. Avoid using epinephrine concurrently with droperidol and haloperidol.
Primaquine: (Moderate) Due to the potential for QT interval prolongation with primaquine, caution is advised with haloperidol. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include haloperidol. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Primidone: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as barbiturates. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Procainamide: (Major) Haloperidol should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Prochlorperazine: (Minor) Caution is advisable when combining haloperidol concurrently with prochlorperazine as concurrent use may increase the risk of QT prolongation and other antipsychotic-related adverse effects including drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Prochlorperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation, such as haloperidol. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the coadministered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Promethazine: (Moderate) Caution is advisable when combining haloperidol concurrently with promethazine as concurrent use may increase the risk of QT prolongation and other antipsychotic-related adverse effects including drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Mild to moderately increased haloperidol concentrations have also been reported when haloperidol was given concomitantly with promethazine. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, promethazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation, such as haloperidol. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the coadministered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Promethazine; Dextromethorphan: (Moderate) Caution is advisable when combining haloperidol concurrently with promethazine as concurrent use may increase the risk of QT prolongation and other antipsychotic-related adverse effects including drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Mild to moderately increased haloperidol concentrations have also been reported when haloperidol was given concomitantly with promethazine. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, promethazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation, such as haloperidol. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the coadministered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Promethazine; Phenylephrine: (Moderate) Caution is advisable when combining haloperidol concurrently with promethazine as concurrent use may increase the risk of QT prolongation and other antipsychotic-related adverse effects including drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Mild to moderately increased haloperidol concentrations have also been reported when haloperidol was given concomitantly with promethazine. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, promethazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation, such as haloperidol. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the coadministered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol, directly counteract the effects of phenylephrine and can counter the desired pharmacologic effect. They also can be used to treat excessive phenylephrine-induced hypertension.
Propafenone: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering propafenone with haloperidol. Propafenone is a Class IC antiarrhythmic which increases the QT interval largely due to prolongation of the QRS interval. QT prolongation and TdP have also been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. In addition, haloperidol is a substrate for CYP2D6 and propafenone is a CYP2D6 substrate/inhibitor. Mild to moderate increases in haloperidol plasma concentrations may occur during concurrent use.
Propofol: (Major) Haloperidol can potentiate the actions of other CNS depressants such as general anesthetics. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Propranolol: (Moderate) Haloperidol should be used cautiously with propranolol due to the possibility of additive hypotension and increased concentrations of propranolol. Propranolol is significantly metabolized by CYP2D6 isoenzymes. A case report of 3 severe hypotension episodes (2 requiring cardiopulmonary resuscitation) has been reported in one 48 year old woman when propranolol and haloperidol have been coadministered. Additive hypotensive effects and haloperidol-mediated CYP2D6 inhibition may have contributed to this interaction.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension. (Moderate) Haloperidol should be used cautiously with propranolol due to the possibility of additive hypotension and increased concentrations of propranolol. Propranolol is significantly metabolized by CYP2D6 isoenzymes. A case report of 3 severe hypotension episodes (2 requiring cardiopulmonary resuscitation) has been reported in one 48 year old woman when propranolol and haloperidol have been coadministered. Additive hypotensive effects and haloperidol-mediated CYP2D6 inhibition may have contributed to this interaction.
Pseudoephedrine: (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Pseudoephedrine; Triprolidine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur. (Moderate) Non-cardiovascular drugs with alpha-blocking activity such as haloperidol directly counteract the effects of pseudoephedrine and can counter the desired pharmacologic effect. They also can be used to treat excessive pseudoephedrine-induced hypertension.
Quazepam: (Moderate) Concomitant administration of quazepam with CNS-depressant drugs, such as antipsychotics, can potentiate the CNS effects of either agent.
Quetiapine: (Major) Quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs that have established causal association with QT prolongation and TdP (torsade de pointes), like haloperidol. 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.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension.
Quinidine: (Contraindicated) Quinidine should be considered contraindicated with haloperidol. QT prolongation and torsade de pointes (TdP) have been observed during both haloperidol and quinidine treatment. Excessive doses (particularly in the overdose setting) of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval; however, quinidine is contraindicated for use with drugs that are CYP2D6 substrates that prolong the QT interval. Pretreatment with quinidine caused peak haloperidol serum concentrations and haloperidol AUC to increase.
Quinine: (Major) Concurrent use of quinine and haloperidol should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. QT prolongation and TdP have also been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Further, quinine is a substrate of CYP3A4 and an inhibitor of CYP2D6 and CYP3A4, the isoenzymes responsible for the metabolism of haloperidol. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and inhibitors of CYP3A4 or CYP2D6. Elevated haloperidol concentrations occurring through inhibition of CYP2D6 or CYP3A4 may increase the risk of adverse effects, including QT prolongation.
Quizartinib: (Major) Concomitant use of quizartinib and haloperidol 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. The intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Ramelteon: (Moderate) An enhanced CNS depressant effect may occur when haloperidol is combined with other CNS depressants including hypnotic drugs such as ramelteon.
Ranolazine: (Moderate) Caution is advisable when combining haloperidol concurrently with ranolazine as concurrent use may increase the risk of QT prolongation and increase haloperidol-related adverse effects. Haloperidol is a CYP2D6 substrate that has been associated with QT prolongation and torsade de pointes (TdP). Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Ranolazine is a CYP2D6 inhibitor associated with dose- and plasma concentration-related increases in the QTc interval. Mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with CYP2D6 inhibitors.
Rasagiline: (Major) Due to opposing effects on central dopaminergic activity, haloperidol and rasagiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to haloperidol. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Relugolix: (Moderate) Caution is advisable when combining haloperidol concurrently with relugolix. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) Caution is advisable when combining haloperidol concurrently with relugolix. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Remifentanil: (Moderate) Concomitant use of remifentanil with other CNS depressants, such as haloperidol, can potentiate the effects of remifentanil on respiration, sedation, and hypotension. A dose reduction of one or both drugs may be warranted.
Ribociclib: (Major) Avoid coadministration of ribociclib with haloperidol due to an increased risk for QT prolongation and torsade de pointes (TdP). Systemic exposure of haloperidol may also be increased resulting in an increase in haloperidol-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Haloperidol is a CYP3A4 substrate that has also been associated with QT prolongation and torsade de pointes (TdP). Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Concomitant use may increase the risk for QT prolongation. In clinical trials, mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with CYP3A4 inhibitors.
Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with haloperidol due to an increased risk for QT prolongation and torsade de pointes (TdP). Systemic exposure of haloperidol may also be increased resulting in an increase in haloperidol-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Haloperidol is a CYP3A4 substrate that has also been associated with QT prolongation and torsade de pointes (TdP). Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Concomitant use may increase the risk for QT prolongation. In clinical trials, mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with CYP3A4 inhibitors.
Rifabutin: (Major) Significant reductions in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and CYP3A4 enzyme-inducing drugs such as carbamazepine or rifampin. Rifabutin is an inducer and a substrate of CYP3A4. Haloperidol dosage adjustments should be made as needed when rifabutin is added or discontinued.
Rifampin: (Major) Limited data suggest that rifampin, a potent CYP inducer, can increase the metabolism and/or reduce the bioavailability of haloperidol. In one small study (n=12), plasma levels of haloperidol were decreased by a mean of 70% and mean scores on the Brief Psychiatric Rating Scale (BPRS) were increased from baseline during concurrent use of rifampin. Discontinuation of rifampin has resulted in a mean 3.3-fold increase in haloperidol concentrations in some instances. Haloperidol dosage adjustments should be made as needed when rifampin is added or discontinued. Prolonged use of CYP inducers such as rifampin in patients receiving haloperidol has resulted in significant reductions in haloperidol plasma concentrations.
Rifapentine: (Moderate) Monitor for decreased efficacy of haloperidol if coadministration with rifapentine is necessary. Coadministration may decrease the exposure of haloperidol. Haloperidol is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased haloperidol plasma concentrations by a mean of 70% and increased mean scores on the Brief Psychiatric Rating Scale from baseline.
Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with haloperidol as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Risperidone: (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.
Ritonavir: (Moderate) Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and inhibitors of CYP3A4 or CYP2D6, such as ritonavir. Elevated haloperidol concentrations may increase the risk of adverse effects. Closely monitor for adverse events when these medications are coadministered.
Rolapitant: (Major) Monitor for haloperidol-related adverse effects, including QT prolongation, if coadministered with rolapitant. Increased exposure to haloperidol may occur. Haloperidol is a CYP2D6 substrate that is individually dose-titrated, and rolapitant is a moderate CYP2D6 inhibitor; the inhibitory effect of rolapitant is expected to persist beyond 28 days for an unknown duration. 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) Consider monitoring electrolytes and ECGs at baseline and periodically during treatment if romidepsin is administered with haloperidol. Romidepsin has been reported to prolong the QT interval. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Ropinirole: (Major) Due to opposing effects on central dopaminergic activity, haloperidol and ropinirole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to haloperidol. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Rotigotine: (Major) Due to opposing effects on central dopaminergic activity, haloperidol and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to haloperidol. Monitor for changes in movement, moods, or behaviors. In addition, coadministration of haloperidol and rotigotine may result in additive sedation.
Sacubitril; Valsartan: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Safinamide: (Major) Due to opposing effects on central dopaminergic activity, haloperidol and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to haloperidol. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Saquinavir: (Contraindicated) Concurrent use of haloperidol and saquinavir boosted with ritonavir is contraindicated due to the risk for cardiac arrhythmias. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as TdP. In addition, saquinavir is an inhibitor of CYP3A4. Elevated haloperidol concentrations occurring through inhibition of CYP3A4 may increase the risk of adverse effects, including QT prolongation.
Secobarbital: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as barbiturates. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Selegiline: (Major) Due to opposing effects on central dopaminergic activity, selegiline and haloperidol may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to haloperidol. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with haloperidol is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Sertraline: (Moderate) Use caution and monitor patients for QT prolongation and increased haloperidol-related adverse effects when administering haloperidol with sertraline. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Sertraline's FDA-approved labeling recommends avoiding concomitant use with drugs known to prolong the QTc interval; however, the risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure). Additionally, sertraline is an inhibitor of CYP2D6. Elevated haloperidol concentrations occurring through inhibition of CYP2D6 may increase the risk of adverse effects, including QT prolongation.
Sevoflurane: (Major) QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with haloperidol include halogenated anesthetics.
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving haloperidol 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. QT prolongation and torsade de pointes have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Sodium Phenylbutyrate: (Moderate) Patients with urea cycle disorders being treated with sodium phenylbutyrate usually should not receive regular treatment with haloperidol. Haloperidol has been reported to increase plasma ammonia levels (hyperammonemia).
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Patients with urea cycle disorders being treated with sodium phenylbutyrate usually should not receive regular treatment with haloperidol. Haloperidol has been reported to increase plasma ammonia levels (hyperammonemia).
Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and haloperidol 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 intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Solifenacin: (Moderate) Consider the potential risk for additive QT prolongation if solifenacin is adminsitered with haloperidol. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. QT prolongation and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Sorafenib: (Major) Avoid coadministration of sorafenib with haloperidol 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. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment; excessive doses (particularly in the overdose setting) or IV administration may be associated with a higher risk of QT prolongation. Sorafenib is also associated with QTc prolongation.
Sotalol: (Major) Concomitant use of sotalol and haloperidol 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. The intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Spironolactone: (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension. (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
St. John's Wort, Hypericum perforatum: (Moderate) St. John's Wort appears to induce several isoenzymes of the hepatic cytochrome P450 enzyme system and could decrease the efficacy of some medications metabolized by these enzymes including haloperidol.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and haloperidol. CNS depressants can potentiate the effects of stiripentol.
Sufentanil: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as sufentanil. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Sunitinib: (Moderate) Caution is advisable when combining haloperidol concurrently with sunitinib. Sunitinib can prolong the QT interval. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Tacrolimus: (Moderate) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with haloperidol as concurrent use may increase the risk of QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Tacrolimus may prolong the QT interval and cause TdP.
Tamoxifen: (Moderate) Concomitant use of tamoxifen and haloperidol 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 intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Tamsulosin: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as haloperidol. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
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) Caution is advisable when combining haloperidol concurrently with telavancin as concurrent use may increase the risk of QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Telavancin has also been associated with QT prolongation.
Telmisartan: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Telmisartan; Amlodipine: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension. (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension. (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Temazepam: (Moderate) Caution should be exercised with simultaneous use of these agents. Haloperidol can potentiate the actions of other CNS depressants, such as the benzodiazepines. Complex sleep behaviors are more likely to occur when temazepam is taken with other CNS depressants. Warn patients of the possibility of drowsiness that may impair performance of potentially hazardous tasks such as driving an automobile or operating machinery.
Terazosin: (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Terbinafine: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as haloperidol.
Tetrabenazine: (Major) Concurrent use of tetrabenazine and haloperidol should be avoided if possible. Tetrabenazine causes a small increase in the corrected QT interval (QTc). QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. The manufacturer of tetrabenazine recommends against concurrent use of tetrabenazine with other drugs known to prolong QTc. In addition, tetrabenazine is a selective, reversible, centrally-acting dopamine depleting drug and haloperidol is a central dopamine antagonist. The risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
Thalidomide: (Major) Avoid the concomitant use of thalidomide with antipsychotics due to the potential for additive sedative effects.
Thiazide diuretics: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension.
Thioridazine: (Contraindicated) Due to the risk for QT prolongation and potential for serious arrhythmias, as well as duplicative antipsychotic effects, the concurrent use of haloperidol with thioridazine is contraindicated. QT prolongation and torsade de pointes have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Thioridazine is associated with an established risk for QT prolongation and torsade de pointes (TdP). Coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Thiothixene: (Major) Caution is advisable during concurrent use of thiothixene and other antipsychotics. Thiothixene 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 other antipsychotics. 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.
Timolol: (Moderate) Haloperidol should be used cautiously with timolol due to the possibility of additive hypotension.
Tipranavir: (Moderate) Tipranavir is a potent inhibitor of CYP2D6 and CYP3A4, the isoenzymes responsible for the metabolism of haloperidol. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and inhibitors of CYP3A4 or CYP2D6. Elevated haloperidol concentrations occurring through inhibition of CYP2D6 or CYP3A4 may increase the risk of adverse effects, including QT prolongation. Until more data are available, it is advisable to closely monitor for adverse events when these medications are co-administered.
Tobacco: (Major) Advise patients to avoid smoking tobacco while taking haloperidol. Tobacco smoking may increase the clearance of haloperidol, which may reduce its efficacy.
Tolcapone: (Major) Due to opposing effects on central dopaminergic activity, haloperidol and COMT inhibitors may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to haloperidol. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Tolterodine: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering tolterodine with haloperidol. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. QT prolongation and TdP have also been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Toremifene: (Major) Avoid coadministration of haloperidol 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. Prolongation of the QT interval and torsade de pointes (TdP) have been observed during haloperidol treatment; excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk. Toremifene has also been shown to prolong the QTc interval in a dose- and concentration-related manner.
Torsemide: (Moderate) Caution is advisable during concurrent use of haloperidol and loop diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension.
Tramadol: (Major) Haloperidol can competitively inhibit the metabolism of tramadol by CYP2D6. Concurrent use of haloperidol and tramadol increases plasma levels of tramadol and decreases the concentration of the active tramadol metabolite. This may lead to decreased analgesic effects of tramadol and possibly increased tramadol-induced side effects, including seizures, due to increased tramadol concentrations and the decrease in seizure threshold caused by haloperidol. Additive CNS depression may also be seen with the concomitant use of tramadol and haloperidol.
Tramadol; Acetaminophen: (Major) Haloperidol can competitively inhibit the metabolism of tramadol by CYP2D6. Concurrent use of haloperidol and tramadol increases plasma levels of tramadol and decreases the concentration of the active tramadol metabolite. This may lead to decreased analgesic effects of tramadol and possibly increased tramadol-induced side effects, including seizures, due to increased tramadol concentrations and the decrease in seizure threshold caused by haloperidol. Additive CNS depression may also be seen with the concomitant use of tramadol and haloperidol.
Trandolapril; Verapamil: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension. Verapamil is a substrate and inhibitor of CYP3A4. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and substrates or inhibitors of CYP3A4 or CYP2D6. Elevated haloperidol concentrations occurring through inhibition of CYP2D6 or CYP3A4 may increase the risk of adverse effects, including QT prolongation.
Trazodone: (Major) Concomitant use of trazodone and haloperidol 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. The intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Treprostinil: (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Triamterene: (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension. (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Triazolam: (Moderate) Haloperidol can potentiate the actions of other CNS depressants, such as benzodiazepines, Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Triclabendazole: (Moderate) Concomitant use of triclabendazole and haloperidol 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 intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Tricyclic antidepressants: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as tricyclic antidepressants (TCAs). Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects. Limited data suggest that haloperidol may inhibit the metabolism of some tricyclic antidepressants, however, the clinical significance of this interaction is uncertain. Haloperidol is an inhibitor of hepatic CYP2D6, and coadministration with many TCAs (which are CYP2D6 substrates) may lead to elevated TCA serum concentrations, potentiating toxicity. Haloperidol has also been associated with a possible risk for QT prolongation and/or torsades de pointes, particularly when excessive doses are used or in overdose. Haloperidol should be used cautiously with other agents that may have this effect (e.g., tricyclic antidepressants).
Trifluoperazine: (Moderate) Caution is advisable when combining haloperidol concurrently with trifluoperazine as concurrent use may increase the risk of QT prolongation and other antipsychotic-related adverse effects including 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. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation, such as haloperidol. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the coadministered antipsychotic agent.
Trihexyphenidyl: (Moderate) The concurrent use of haloperidol with trihexyphenidyl is beneficial for many patients, as these anticholinergic agents treat drug-induced extrapyramidal symptoms. However, the anticholinergic effects of trihexyphenidyl may be additive to those of haloperidol, and may increase the incidence of dry mouth, constipation, or heat intolerance. Advise patients to promptly report gastrointestinal complaints, fever, or heat intolerance.
Triprolidine: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Triptorelin: (Major) Avoid coadministration of triptorelin with haloperidol due to the risk of reduced efficacy of triptorelin; QT prolongation may also occur. Haloperidol can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog. Additionally, QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment; excessive doses (particularly in the overdose setting) or IV administration may be associated with a higher risk. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
Tucatinib: (Moderate) Monitor for haloperidol-related adverse effects, including QT prolongation, if coadministered with tucatinib. Concurrent use may result in increased serum concentrations of haloperidol. Haloperidol is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor.
Valproic Acid, Divalproex Sodium: (Major) Concomitant use of other CNS depressants, such as haloperidol, with valproic acid can cause additive CNS depression. Haloperidol, used concomitantly with valproic acid, can increase CNS depression and also can lower the seizure threshold, requiring change in the valproic acid dose.
Valsartan: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of haloperidol and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension. (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Vandetanib: (Major) Avoid coadministration of vandetanib with haloperidol 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. Prolongation of the QT interval and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Vardenafil: (Moderate) Concomitant use of vardenafil and haloperidol 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 intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
Vasodilators: (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
Vasopressin, ADH: (Moderate) Monitor hemodynamics and adjust the dose of vasopressin as needed when used concomitantly with drugs suspected of causing syndrome of inappropriate antidiuretic hormone (SIADH), such as haloperidol. Use together may increase the pressor and antidiuretic effects of vasopressin.
Vemurafenib: (Major) Vemurafenib has been associated with QT prolongation. If vemurafenib and another drug, such as haloperidol, that is associated with a possible risk for QT prolongation and torsade de pointes (TdP) must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Also, haloperidol is a CYP2D6 and 3A4 substrate, while vemurafenib is a weak CYP2D6 inhibitor and a CYP3A4 substrate/inducer; therefore, altered concentrations of haloperidol may occur with concomitant use. Elevated haloperidol concentrations occurring through inhibition of CYP2D6 or CYP3A4 may increase the risk of adverse effects, including QT prolongation.
Venlafaxine: (Moderate) Caution is advisable when combining haloperidol concurrently with venlafaxine as concurrent use may increase the risk of QT prolongation and haloperidol-related adverse effects. A haloperidol dose reduction may be necessary. Mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with venlafaxine. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Venlafaxine administration is associated with a possible risk of QT prolongation; torsade de pointes (TdP) has reported with postmarketing use.
Verapamil: (Moderate) In general, antipsychotics like haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension. Verapamil is a substrate and inhibitor of CYP3A4. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and substrates or inhibitors of CYP3A4 or CYP2D6. Elevated haloperidol concentrations occurring through inhibition of CYP2D6 or CYP3A4 may increase the risk of adverse effects, including QT prolongation.
Voclosporin: (Moderate) Concomitant use of voclosporin and haloperidol 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. QT prolongation and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Concurrent use of clarithromycin and haloperidol should be avoided if possible. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval. Because clarithromycin is also associated with an increased risk for QT prolongation and TdP, the need to coadminister clarithromycin with drugs known to prolong the QT interval should be done with a careful assessment of risks versus benefits. Clarithromycin is an inhibitor of CYP3A4. Elevated haloperidol concentrations occurring through inhibition of CYP3A4 or CYP2D6 may increase the risk of adverse effects, including QT prolongation.
Voriconazole: (Moderate) Use voriconazole with caution in combination with haloperidol as concurrent use may increase the risk of QT prolongation and haloperidol-related adverse effects. A haloperidol dose reduction may be necessary. Voriconazole is a strong CYP3A4 inhibitor that has been associated with QT prolongation and rare cases of torsade de pointes. Haloperidol is a CYP3A4 substrate; QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with CYP3A4 inhibitors.
Vorinostat: (Moderate) Caution is advisable when combining haloperidol concurrently with vorinostat as concurrent use may increase the risk of QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Vorinostat therapy is also associated with a risk of QT prolongation.
Warfarin: (Moderate) Haloperidol can decrease the anticoagulation effects of warfarin. If these drugs are coadministered, monitor INR and adjust warfarin doses as needed.
Zafirlukast: (Moderate) Zafirlukast is an inhibitor of CYP3A4, one of the isoenzymes responsible for the metabolism of haloperidol. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and substrates or inhibitors of CYP3A4. Until more data are available, it is advisable to closely monitor for adverse events when these medications are co-administered.
Zaleplon: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as anxiolytics, sedatives, and hypnotics, and they should be used cautiously in combination.
Ziconotide: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as haloperidol. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Ziprasidone: (Major) Concomitant use of ziprasidone and haloperidol should be avoided if possible. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. QT prolongation and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval. In addition, coadministration of ziprasidone and haloperidol 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.
Zolpidem: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as anxiolytics, sedatives, and hypnotics, and they should be used cautiously in combination.
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.
How Supplied
Haldol/Haldol Decanoate/Haloperidol/Haloperidol Decanoate/Haloperidol Lactate Intramuscular Inj Sol: 1mL, 5mg, 50mg, 100mg
Haldol/Haloperidol Oral Tab: 0.5mg, 1mg, 2mg, 5mg, 10mg, 20mg
Haloperidol/Haloperidol Lactate Oral Sol: 1mL, 2mg
Maximum Dosage
100 mg/day PO. 20 mg/day IM of haloperidol lactate. Clinical experience with haloperidol decanoate doses greater than 450 mg/month IM is limited.
Geriatric100 mg/day PO. 20 mg/day IM of haloperidol lactate. Clinical experience with haloperidol decanoate doses greater than 450 mg/month IM is limited.
AdolescentsWeighing more than 40 kg: 15 mg/day PO for Tourette's syndrome; there is no stated maximum dosage for adolescents with other indications; dosages exceeding 15 mg/day PO are rarely needed in adults but severely disturbed psychotic adults may require higher dosages; adult dosages up to 100 mg/day PO have been used in severe refractory cases. Safe and effective use of haloperidol injections has not been established (adult haloperidol lactate Max: 20 mg/day IM).
Weighing 40 kg or less: 0.15 mg/kg/day PO for most indications; severely psychotic patients may require higher doses (suggested Max: 6 mg/day PO for non-psychotic behaviors); 15 mg/day PO for Tourette's syndrome. Safe and effective use of haloperidol injections has not been established (adult haloperidol lactate Max: 20 mg/day IM).
3 to 12 years and weighing 15 to 40 kg: 0.15 mg/kg/day PO for most indications; severely psychotic children may require higher doses (suggested Max: 6 mg/day PO for non-psychotic behaviors); 15 mg/day PO for Tourette's syndrome. Safe and effective use of haloperidol injections has not been established (adult haloperidol lactate Max: 20 mg/day IM).
1 to 2 years or weighing less than 15 kg: Safety and efficacy have not been established.
Safety and efficacy have not been established.
NeonatesSafety and efficacy have not been established.
Mechanism Of Action
The precise mechanism of action of conventional antipsychotics, such as haloperidol, is unknown; however, the therapeutic effect in treating the positive symptoms of schizophrenia (e.g., hallucinations, delusions) is thought to occur from blockade of central postsynaptic dopamine (D-2) receptors in the mesolimbic pathway. By antagonizing dopamine in all areas of the brain, conventional antipsychotics are effective for treating the positive symptoms of schizophrenia, but can cause a variety of adverse effects. In addition, therapeutic effects on the negative symptoms (e.g., social withdrawal, blunted affect) and cognitive symptoms of schizophrenia relate to increased dopamine activity in the prefrontal cortex which may, in part, account for the general lack of improvement in these symptoms observed with D-2 blockers such as conventional agents. Antipsychotics 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 of the therapeutic effects of antipsychotics. Induction of synaptic plasticity has been well-documented with haloperidol in the striatum, where the highest concentration of D-2 receptors exist.
In the nigrostriatal pathway, antipsychotic-induced dopamine blockade can lead to pseudoparkinsonism and other extrapyramidal symptoms (e.g., dystonic reactions, akathisia). Dopamine receptor blockade in the tuberoinfundibular tract results in prolactin release, which can lead to adverse effects related to hyperprolactinemia such as weight gain and menstrual irregularity. Haloperidol has a negligible affinity for muscarinic receptors, resulting in only weak anticholinergic effects. Haloperidol also has a weak affinity for alpha-1 and H-1 receptors, minimizing the likelihood of orthostatic hypotension, dizziness, reflex tachycardia, and sedation compared to many other antipsychotics.
Pharmacokinetics
Haloperidol is administered orally, intramuscularly, and intravenously (immediate-release lactate injection only). Injectable formulations are not FDA-approved for intravenous administration; if the immediate-release lactate injection is administered intravenously, the ECG should be monitored for QT prolongation and arrhythmias. Haloperidol decanoate dissolved in sesame oil is given by deep intramuscular injection, which results in slow and sustained release of haloperidol. Haloperidol is 92% plasma protein-bound, predominately to alpha-1-acid glycoprotein. It appears to exhibit extensive first pass metabolism. Haloperidol is extensively metabolized in the liver through N-dealkylation to inactive metabolites, and metabolism by glucuronidation also occurs. Reduction to hydroxyhaloperidol, an active metabolite, also occurs. CYP2D6 and CYP3A4 are the primary isoenzymes involved in the metabolism of haloperidol. Slow metabolizers of CYP2D6 appear to be at increased risk of experiencing extrapyramidal symptoms due to delayed clearance of the drug. About 40% of a dose is excreted renally within 5 days, with 1% appearing as unchanged drug. Approximately 15% is eliminated through biliary excretion. The elimination half-life for immediate-release products ranges between 12 and 37 hours (reported average: 16 hours) in adult patients.[28307] [33492] [55159] [55214] [58479]
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP2D6, CYP3A4
CYP2D6 and CYP3A4 are the primary CYP isoenzymes involved in the metabolism of haloperidol, although limited data suggest that CYP1A2 may also play a role. Inhibition of one or more of these metabolic pathways may result in increased haloperidol concentrations and the potential for QT prolongation. Mild to moderate increases in haloperidol concentrations have been reported during concomitant use of haloperidol and substrates or inhibitors of CYP3A4 or CYP2D6. Significant reductions in haloperidol concentrations have occurred with the use of some enzyme-inducing drugs and tobacco. In addition to the concern of drug-drug interactions, slow metabolizers of CYP2D6 appear to be at increased risk of experiencing extrapyramidal symptoms and other adverse events due to delayed clearance of the drug. The impact of haloperidol on CYP2D6 and CYP3A4 is unclear. Some pharmacokinetic data suggest that haloperidol may inhibit CYP2D6 and CYP3A4; however, other data suggest that the risk of clinically significant inhibition is low. Because the strength of inhibition is not clear, use caution when co-administering haloperidol with drugs that are metabolized by CYP3A4 or CYP2D6.[28307] [43715] [56381] [56382] [56383] [57203]
Following oral administration in adults, systemic absorption occurs in 60 to 90 minutes. Peak plasma concentrations are attained in 2 to 6 hours. First-pass metabolism in the liver and potentially other factors reduce the bioavailability of haloperidol to approximately 40% to 70%, with an average of approximately 60%. Wide intersubject variation in Cmax, AUC, and clearance values has been reported after a single 5 mg oral dose of haloperidol administered to 28 healthy adult males.[55159] [58484]
Intravenous RouteImmediate-release lactate injection solution: When used intravenously, peak plasma concentrations are obtained almost immediately after injection and decrease rapidly for about 1 hour during the distribution phase before reaching the elimination phase, where plasma concentrations decrease more slowly. This formulation is only approved for intramuscular administration; if administered intravenously, the ECG should be monitored for QT prolongation and arrhythmias.[28307] [55159]
Intramuscular RouteImmediate-release lactate injection solution: In adults, peak plasma concentrations occur in 20 to 40 minutes.[55159]
Decanoate depot in oil injection: Following deep intramuscular injection in adults, the plasma concentrations of haloperidol gradually rise; peak plasma concentrations are achieved after about 6 days and decrease after that. Steady state is achieved after the third of fourth dose. The apparent half-life of haloperidol decanoate is about 3 weeks. Although the pharmacokinetics of haloperidol decanoate are linear for doses less than 450 mg, parameters can vary between patients.[33492]
Pregnancy And Lactation
According to the manufacturer, breast-feeding should be avoided during treatment with oral or injectable haloperidol. Haloperidol is excreted into breast milk. However, some experts have concluded that haloperidol use is compatible with breast-feeding. In one small study, developmental delays were reported in some nursing infants following combined use of haloperidol and chlorpromazine, while monotherapy did not result in this outcome. Conversely, in 2 women who received 5 mg/day of haloperidol plus olanzapine or amisulpride during pregnancy and breast-feeding, the breastfed infants exhibited normal development, and no adverse effects were noted during the 11- to 13-month follow-up period. In other case reports of breast-feeding during haloperidol monotherapy or combination therapy with imipramine or trihexyphenidyl and a haloperidol dose in the general range of 7.5 mg/day to 15 mg/day, age-appropriate development of the breastfed infants occurred during the follow-up period (range: 12 months to 8 years). Haloperidol may cause elevated prolactin levels and galactorrhea and has the potential to alter proper lactation in some patients. Some data suggest that postnatal women are more sensitive to the prolactin-elevating effects of antipsychotics than nonpuerperal women. Due to individual variability in response to antipsychotics, it may be prudent to continue the existing regimen if ongoing treatment is deemed necessary during breast-feeding; however, alternate medications for consideration include atypical agents such as olanzapine or quetiapine. Data regarding the safety of atypical antipsychotics during breast-feeding are limited and chronic administration of any antipsychotic during breast-feeding should be avoided if possible. Regardless of the antipsychotic used, the nursing infant should be closely monitored for excessive drowsiness, lethargy, and developmental delays. Combination treatment with antipsychotics may increase the risk of these adverse events.