Orap

First Generation Antipsychotics

Oral Administration

May give as a single daily dose or in divided doses to increase tolerability.
Administer with a full glass of water.
Patients should avoid grapefruit juice during pimozide treatment.

Severe

visual impairment / Early / 2.7-4.0
torticollis / Delayed / 0-2.7
tardive dyskinesia / Delayed / Incidence not known
neuroleptic malignant syndrome / Delayed / Incidence not known
torsade de pointes / Rapid / Incidence not known
bradycardia / Rapid / Incidence not known
SIADH / Delayed / Incidence not known
water intoxication / Delayed / Incidence not known
seizures / Delayed / Incidence not known
aplastic anemia / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
thromboembolism / Delayed / Incidence not known
pulmonary embolism / Delayed / Incidence not known

Moderate

dyskinesia / Delayed / 8.0-8.0
akathisia / Delayed / 8.0-8.0
constipation / Delayed / 4.0-4.0
impotence (erectile dysfunction) / Delayed / 3.0-3.0
dystonic reaction / Delayed / 0-2.7
dysphagia / Delayed / 0-2.7
dysarthria / Delayed / 2.0-2.0
photophobia / Early / 1.0-1.0
pseudoparkinsonism / Delayed / 10.0
sinus tachycardia / Rapid / Incidence not known
QT prolongation / Rapid / Incidence not known
palpitations / Early / Incidence not known
hypotension / Rapid / Incidence not known
orthostatic hypotension / Delayed / Incidence not known
hypertension / Early / Incidence not known
chest pain (unspecified) / Early / Incidence not known
infertility / Delayed / Incidence not known
urinary retention / Early / Incidence not known
hyperprolactinemia / Delayed / Incidence not known
galactorrhea / Delayed / Incidence not known
priapism / Early / Incidence not known
ejaculation dysfunction / Delayed / Incidence not known
gingival hyperplasia / Delayed / Incidence not known
hyponatremia / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
neutropenia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
cataracts / Delayed / Incidence not known
blurred vision / Early / Incidence not known
hyperthermia / Delayed / Incidence not known

Mild

drowsiness / Early / 7.0-25.0
asthenia / Delayed / 0-13.8
weight loss / Delayed / 1.0-10.0
xerostomia / Early / 5.0-5.0
myalgia / Early / 2.7-3.0
headache / Early / 0-2.7
hyperkinesis / Delayed / 0-2.7
tremor / Early / 0-2.7
hypersalivation / Early / 0-2.7
rash / Early / 0-2.7
diarrhea / Early / 1.0-1.0
appetite stimulation / Delayed / 1.0-1.0
polydipsia / Early / 0-1.0
dysgeusia / Early / 1.0-1.0
syncope / Early / Incidence not known
dizziness / Early / Incidence not known
menstrual irregularity / Delayed / Incidence not known
breast enlargement / Delayed / Incidence not known
increased urinary frequency / Early / Incidence not known
mastalgia / Delayed / Incidence not known
amenorrhea / Delayed / Incidence not known
gynecomastia / Delayed / Incidence not known
libido decrease / Delayed / Incidence not known
nocturia / Early / Incidence not known
nausea / Early / Incidence not known
vomiting / Early / Incidence not known
anorexia / Delayed / Incidence not known
weight gain / Delayed / Incidence not known
purpura / Delayed / Incidence not known
fever / Early / Incidence not known
skin irritation / Early / Incidence not known
hyperhidrosis / Delayed / Incidence not known
hypothermia / Delayed / Incidence not known

Dementia, geriatric

Pimozide should be used with caution in geriatric patients because of the possibility of reduced drug clearance and the greater likelihood of concomitant serious health conditions. Geriatric patients may be more susceptible to the actions and adverse effects of conventional antipsychotics, including tardive dyskinesia, prolongation of the QT interval, dystonia, and a risk for falls and fractures. Initiate treatment with lower doses followed by careful dosage titration and close monitoring. A lower target dose for pimozide should be considered. Antipsychotics are not FDA-approved for the treatment of dementia-related psychosis in geriatric patients. A boxed warning in the label of all antipsychotics outlines the significantly increased incidence of cerebrovascular events (e.g., stroke, transient ischemic attack), including fatal events, reported in the elderly with dementia-related psychosis receiving antipsychotics compared to placebo. Two population-based, retrospective cohort studies evaluated the risk of death in elderly patients with dementia receiving conventional antipsychotics. One of the studies found that those receiving atypical antipsychotics had an increase in mortality compared to the placebo group and that those receiving conventional antipsychotics had a marginally higher risk of death compared to the atypical antipsychotic group. Investigators from a separate study reported that the risk of death (all-cause mortality) in the conventional antipsychotic group was comparable to and possibly greater than the risk of death in the atypical antipsychotic group. Deaths due to cancer and cardiac disease carried the highest relative risk. According to the Beers Criteria, antipsychotics are considered potentially inappropriate medications (PIMs) in elderly patients, and use should be avoided except for treating schizophrenia or bipolar disorder, and for short-term use as antiemetics during chemotherapy. Avoid pimozide use in geriatric patients with the following conditions due to the potential for symptom exacerbation or adverse effects: Parkinson's disease (symptom exacerbation), delirium (possible new-onset or worsening delirium), and dementia (adverse CNS effects). There is an increased risk of stroke and a greater rate of cognitive decline and mortality in persons with dementia receiving antipsychotics, and the Beers expert panel recommends avoiding antipsychotics to treat delirium- or dementia-related behavioral problems unless non-pharmacological options have failed or are not possible and the patient is a substantial threat to self or others. The Beers Panel recommends avoiding antipsychotics in elderly patients with a history of falls or fractures, unless safer alternatives are not available, as antipsychotics can cause ataxia, impaired psychomotor function, syncope, and additional falls. If an antipsychotic must be used, consider reducing the use of other CNS-active medications that increase the risk of falls and fractures and implement strategies to reduce fall risk. Because antipsychotics can cause or exacerbate hyponatremia and SIADH and the elderly are at increased risk of developing these conditions, sodium levels should be closely monitored when starting or changing dosages of antipsychotics in older adults. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). An antipsychotic should generally be used only for the conditions listed in the guidelines (e.g., schizophrenia, mood disorder, Tourette's disorder) and that meet the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for use. There is an increased risk of morbidity and mortality in elderly patients treated with antipsychotics for dementia-related psychosis. Therefore, identify and address all possible causes of behavioral or psychological symptoms of dementia (BPSD) before considering an antipsychotic. To initiate antipsychotic therapy, the patient must be a danger to self or others and 1) symptoms due to mania or psychosis or 2) the plan of care includes documentation of attempted behavioral interventions (except in an emergency). Limit emergency treatment to 7 days or less with evaluation and documentation within 7 days which identifies and addresses contributors/causes. For acute conditions persisting beyond 7 days, non-pharmacologic interventions must be attempted, unless clinically contraindicated, and documented. Treatment of non-acute, chronic, or prolonged BPSD must meet all of the OBRA criteria for BPSD treatment and include monitoring that ensures the behavioral symptoms are not due to a treatable or correctable medical condition, are not due to correctable environmental or treatable psychological stressors alone, and that there is documented evidence of persistence. The LTCF must evaluate the appropriateness of the antipsychotic during or within 2 weeks of admission for a newly admitted resident on an antipsychotic. In all cases, the lowest possible dose and the shortest duration should be prescribed. OBRA provides general dosing guidance for antipsychotic treatment of BPSD. Monitoring of antipsychotics should include evaluation of ongoing effectiveness, the rationale for use, and potential adverse effects (e.g., anticholinergic effects, neurological symptoms, metabolic syndrome, cardiac effects). Antipsychotics are subject to periodic review for effectiveness, necessity, and the potential for gradual dose reduction (GDR) or discontinuation. Refer to the OBRA guidelines for complete information.

Orap

Rx

High potency oral antipsychotic; associated with QT prolongation and cardiac arrhythmias; many contraindicated drug interactions
Reserved for use for motor and phonic tics of Tourette's syndrome refractory to standard treatment
As with all antipsychotics, increased mortality risk in elderly patients treated for dementia-related psychosis

For the treatment of Tourette's syndrome or chronic tic disorders† not responding to standard therapy. Oral dosage Adults

Initially, 1 to 2 mg per day PO in divided doses or as a single dose. Use a lower initial dose for geriatric patients. Increase gradually every other day as necessary. Max: 0.2 mg/kg/day or 10 mg/day PO, whichever is less. Due to the partial metabolism of pimozide by CYP2D6 and the potential for toxicity, CYP2D6 genotyping is recommended by the manufacturer. At doses above 4 mg/day PO, CYP2D6 genotyping should be performed. For CYP2D6 poor metabolizers, allow 14 days between dose increases and do not exceed 4 mg/day PO. The American Academy of Neurology (AAN) practice guideline states that pimozide is possibly more likely than placebo to reduce tic severity in those with Tourette's syndrome or chronic tic disorders; however, there is insufficient evidence to determine the efficacy of pimozide relative to other antipsychotics used to treat tics.

Adolescents

Initially, 0.05 mg/kg/day PO at bedtime. Gradually increase every third day as necessary. Max: 0.2 mg/kg/day or 10 mg/day, whichever is less. At doses above 0.05 mg/kg/day, CYP2D6 genotyping should be performed. For pediatric patients who are CYP2D6 poor metabolizers, dosage increases occur no earlier than 14 days and do not exceed 0.05 mg/kg/day. The American Academy of Neurology (AAN) practice guideline states that pimozide is possibly more likely than placebo to reduce tic severity in those with Tourette's syndrome or chronic tic disorders; however, there is insufficient evidence to determine the efficacy of pimozide relative to other antipsychotics used to treat tics.

Children 8 to 12 years

Reliable dose-response data are not available; most pediatric patients in efficacy trials were 12 years and older. Initiate at a dose of 0.05 mg/kg PO once daily at bedtime. The dose may be increased every third day. Max: 0.2 mg/kg/day or 10 mg/day, whichever is less. At doses above 0.05 mg/kg/day, CYP2D6 genotyping should be performed. For CYP2D6 poor metabolizers, dosage increases should occur no earlier than 14 days; do not exceed 0.05 mg/kg/day. In 1 small study, pimozide dosages of 1 to 6 mg/day after titration were effective in children 7 years of age or older. The maximum dose was 6 mg/day or 0.2 mg/kg/day, whichever was less. The American Academy of Neurology (AAN) practice guideline states that pimozide is possibly more likely than placebo to reduce tic severity in those with Tourette's syndrome or chronic tic disorders; however, there is insufficient evidence to determine the efficacy of pimozide relative to other antipsychotics used to treat tics.

For the treatment of delusions of parasitosis† not responding to standard therapy. Oral dosage Adults

Some literature suggests an initial dose of 1 to 2 mg per day PO with increases of 1 to 2 mg on alternate days or weekly as needed. However, due to a high incidence of extrapyramidal symptoms, a more conservative starting dosage of 0.5 to 1 mg per day with 1 mg increment increases every week should be considered. A low initial dose is advisable in geriatric patients. The doses may be divided or given as a single daily dose as tolerated by the patient. Improvement often occurs within the dose range of 2 to 4 mg per day. Doses above 4 to 6 mg per day increase the risk of extrapyramidal symptoms. Max: 10 mg/day PO per product labeling due to the potential for QT prolongation with higher doses. One author notes that most patients can be tapered off of the medication after 2 to 3 months of use, and thereafter treated on an episodic basis if necessary. The suggested tapering regimen consists of continuing treatment for at least 1 month after the effective dose is achieved, then gradually tapering off by 1 mg on a weekly or less frequent basis. The dosage of pimozide should continue to be decreased until the minimum effective dosage is obtained or the drug can be discontinued. Due to partial metabolism of pimozide by CYP2D6 and the potential for toxicity, CYP2D6 genotyping is recommended by the manufacturer. For adults who are poor metabolizers of CYP2D6, dosage increases should occur no earlier than 14 days, and the maximum daily dose should not exceed 4 mg/day PO.

For the treatment of schizophrenia† not responding to standard therapy. Oral dosage Adults

Initially, 0.5 to 2 mg per day as a single dose or in divided doses. A low initial dose is advisable in geriatric patients. Thereafter, may increase gradually (e.g., 1 mg increments every other day) as tolerated to an effective dose. When possible, a slow titration is recommended due to the dose-related incidence of extrapyramidal symptoms. In an analysis of 16 clinical trials of pimozide for schizophrenia, the mean effective dose was 7.5 mg/day PO. Max: 0.2 mg/kg/day or 10 mg/day PO, whichever is less, per product labeling. CYP2D6 genotyping is recommended for doses exceeding 4 mg/day PO. For adults who are poor metabolizers of CYP2D6, dosage increases should occur no earlier than 14 days, and the maximum daily dose should not exceed 4 mg/day PO.

†Indicates off-label use

Hepatic Impairment

No specific guidelines for dosage adjustment are available. Administer cautiously to patients with impairment of liver function due to extensive hepatic metabolism.

Renal Impairment

No specific guidelines are available; the manufacturer advises caution in administering pimozide to those with renal impairment because the metabolites are excreted primarily by the kidneys.

Abarelix: (Contraindicated) Concurrent use is contraindicated. Pimozide has been specifically established to have a causal association with QT prolongation and torsade de pointes (TdP). Pimozide should not be administered with other medications known to cause QT prolongation, including abarelix.
Abiraterone: (Moderate) Caution is advisable during concurrent use of pimozide and moderate CYP2D6 inhibitors such as abiraterone. Pimozide is metabolized primarily through CYP3A4, and to a lesser extent CYP1A2 and CYP2D6. While the manufacturer has provided no guidance regarding pimozide use with mild or moderate CYP2D6 inhibitors, concurrent use of the drug with more potent inhibitors of CYP2D6 is contraindicated. Elevated concentrations of pimozide can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of other central nervous system (CNS) depressants, such as pimozide, can potentiate the effects of dihydrocodeine and may lead to additive CNS or respiratory depression, or profound sedation. If these agents are used together, a reduced initial dosage of dihydrocodeine is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
Acetaminophen; Chlorpheniramine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as pimozide, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine may be required. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Acetaminophen; Diphenhydramine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include pimozide.
Acetaminophen; Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as pimozide, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking pimozide, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider using a lower pimozide dose. Monitor patients for sedation and respiratory depression.
Acetazolamide: (Moderate) Caution is advisable during concurrent use of pimozide and acetazolamide as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Acrivastine; Pseudoephedrine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Acyclovir: (Moderate) Monitor for pimozide-related adverse reactions, including QT prolongation and ventricular arrhythmias, if coadministered with acyclovir. Coadministration may result in elevated pimozide concentrations. Pimozide is metabolized primarily through CYP3A, and to a lesser extent CYP1A2 and CYP2D6; acyclovir is a weak CYP1A2 inhibitor.
Adagrasib: (Contraindicated) Concurrent use of pimozide and adagrasib is contraindicated. Coadministration may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Additive QT prolongation may also occur. Pimozide is a CYP3A and CYP2D6 substrate and adagrasib is a strong CYP3A and moderate CYP2D6 inhibitor.
Albuterol; Budesonide: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Aldesleukin, IL-2: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psyhcotropic activity. Use with caution.
Alfentanil: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including opiate agonists.
Alfuzosin: (Contraindicated) Because of the potential for QT prolongation and torsade de pointes (TdP), use of alfuzosin with pimozide is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and TdP. Based on electrophysiology studies, alfuzosin has a slight effect to prolong the QT interval. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Alprazolam: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including benzodiazepines.
Amantadine: (Moderate) Although the mechanism of amantadine is not clear, it may potentiate the actions of dopamine. Since pimozide is a dopamine antagonist, this drug should be avoided when possible in patients with Parkinson's disease who require amantadine therapy.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Amiodarone: (Contraindicated) Avoid concomitant use of pimozide and amiodarone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation.
Amisulpride: (Contraindicated) Coadministration of pimozide with amisulpride is contraindicated due to the risk of additive QT prolongation and torsade de pointes (TdP). Pimozide is associated with a well-established risk of QT prolongation and TdP. Amisulpride causes dose- and concentration- dependent QT prolongation.
Amlodipine; Celecoxib: (Moderate) A dosage adjustment may be warranted for pimozide if coadministered with celecoxib due to the potential for celecoxib to enhance the exposure and toxicity of pimozide. Celecoxib is a CYP2D6 inhibitor, and pimozide is a CYP2D6 substrate.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Amoxapine: (Major) Avoid co-administration of amoxapine and pimozide if possible, due to additive CNS effects. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are also potential problems with the combined use of amoxapine and antipsychotics.
Amoxicillin; Clarithromycin; Omeprazole: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of macrolide antibiotics with pimozide is contraindicated.
Amphotericin B lipid complex (ABLC): (Major) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as amphotericin B. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia.
Amphotericin B liposomal (LAmB): (Major) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as amphotericin B. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia.
Amphotericin B: (Major) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as amphotericin B. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia.
Anagrelide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). TdP and ventricular tachycardia have been reported during post-marketing use of anagrelide. Because of the potential for TdP, concurrent use is contraindicated.
Apomorphine: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of apomorphine with pimozide is contraindicated. Apomorphine is also associated with QT prolongation. In addition, the use of pimozide may counteract the effectiveness of apomorphine due to its dopamine antagonist actions. Both agents also cause sedation.
Aprepitant, Fosaprepitant: (Contraindicated) Use of aprepitant or fosaprepitant is contraindicated for use in patients taking pimozide. Inhibition of CYP3A by aprepitant could result in elevated plasma concentrations of pimozide, which is a CYP3A substrate, potentially causing serious or life-threatening reactions, such as QT prolongation, a known adverse reaction of pimozide.
Aripiprazole: (Contraindicated) Avoid concomitant use of aripiprazole and pimozide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. If use is necessary in patients receiving both a CYP3A inhibitor plus pimozide, an aripiprazole dosage adjustment may be required. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects; use may also increase the risk for QT/QTc prolongation and TdP. Aripiprazole is a CYP2D6 and CYP3A substrate, pimozide is a weak CYP2D6 inhibitor, and both medications have been associated with QT/QTc prolongation.
Arsenic Trioxide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of arsenic trioxide with pimozide is contraindicated.
Artemether; Lumefantrine: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of lumefantrine with pimozide is contraindicated.
Asciminib: (Major) Avoid concomitant use of pimozide and asciminib. Concomitant use may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is CYP3A substrate, and asciminib is a weak CYP3A inhibitor.
Asenapine: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Asenapine has a risk of QT prolongation and is contraindicated with pimozide. Concurrent use of pimozide with atypical agents may increase the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as pimozide, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine may be required. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
Aspirin, ASA; Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as pimozide, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking pimozide, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider using a lower pimozide dose. Monitor patients for sedation and respiratory depression.
Atazanavir; Cobicistat: (Contraindicated) Coadministration of pimozide with cobicistat is contraindicated. Cobicistat is a strong inhibitor of CYP3A4 and a CYP2D6 inhibitor; plasma concentrations of drugs extensively metabolized by these enzymes, such as pimozide, are expected to increase with concurrent use. Elevated plasma concentrations of pimozide have been associated with QT prolongation and serious cardiovascular adverse events including death due to torsade de pointes.
Atenolol; Chlorthalidone: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Atomoxetine: (Contraindicated) Avoid concomitant use of pimozide and atomoxetine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Atropine; Difenoxin: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including diphenoxylate/difenoxin.
Avacopan: (Major) Avoid concomitant use of pimozide and avacopan. Concomitant use may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is CYP3A substrate, and avacopan is a weak CYP3A inhibitor.
Azelastine; Fluticasone: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Azilsartan; Chlorthalidone: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Azithromycin: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of macrolide antibiotics with pimozide is contraindicated.
Beclomethasone: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Bedaquiline: (Contraindicated) Due to the potential for torsade de pointes (TdP), concurrent use of pimozide with bedaquiline is contraindicated. Prolongation of the QT interval is known to occur with both drugs, and pimozide is also associated with a well-established risk for TdP.
Belladonna; Opium: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including opiate agonists.
Belumosudil: (Major) Avoid concomitant use of pimozide and belumosudil. Concomitant use may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is CYP3A substrate and belumosudil is a weak CYP3A inhibitor.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with pimozide may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with pimozide 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 pimozide, reduce initial dosage and titrate to clinical response. If pimozide is initiated a patient taking an opioid agonist, use a lower initial dose of pimozide and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Benzodiazepines: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including benzodiazepines.
Berotralstat: (Major) Concurrent use of pimozide and berotralstat should be avoided. Coadministration may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is metabolized primarily through CYP3A4 and to a lesser extent by CYP2D6; berotralstat is a moderate CYP3A4 and CYP2D6 inhibitor.
Betamethasone: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Bicalutamide: (Major) Concurrent use of pimozide and bicalutamide should be avoided. Coadministration may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is metabolized primarily through CYP3A4, and bicalutamide is a weak CYP3A4 inhibitor.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Contraindicated) Avoid concomitant use of metronidazole and pimozide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Contraindicated) Avoid concomitant use of metronidazole and pimozide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Brexpiprazole: (Major) Caution is advisable during concurrent use of brexpiprazole with other antipsychotics such as pimozide. The risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, or seizures may be increased during combined use; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is deemed necessary. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Bromocriptine: (Major) The prolactin-lowering effect of bromocriptine at the anterior pituitary may be antagonized by medications that increase prolactin levels, such as the pimozide. In addition, bromocriptine, a dopamine agonist, may diminish the effectiveness of central dopamine antagonists such as the antipsychotics.
Brompheniramine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Brompheniramine; Phenylephrine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Brompheniramine; Pseudoephedrine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Budesonide: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Budesonide; Formoterol: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Bumetanide: (Moderate) Caution is advisable during concurrent use of pimozide and loop diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Buprenorphine: (Contraindicated) Avoid concomitant use of pimozide and buprenorphine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Buprenorphine; Naloxone: (Contraindicated) Avoid concomitant use of pimozide and buprenorphine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Bupropion: (Contraindicated) Coadministration of pimozide and bupropion is contraindicated due to the potential for increased pimozide exposure. Elevated concentrations of pimozide can lead to QT prolongation, ventricular arrhythmias, and sudden death. The risk of seizure may also be increased as both drugs lower the seizure threshold. Bupropion is a strong CYP2D6 inhibitor; pimozide is a CYP2D6 substrate. Coadministration of pimozide with another strong CYP2D6 inhibitor increased the pimozide AUC by 151%.
Bupropion; Naltrexone: (Contraindicated) Coadministration of pimozide and bupropion is contraindicated due to the potential for increased pimozide exposure. Elevated concentrations of pimozide can lead to QT prolongation, ventricular arrhythmias, and sudden death. The risk of seizure may also be increased as both drugs lower the seizure threshold. Bupropion is a strong CYP2D6 inhibitor; pimozide is a CYP2D6 substrate. Coadministration of pimozide with another strong CYP2D6 inhibitor increased the pimozide AUC by 151%.
Buspirone: (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for sedation.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as pimozide, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine may be required. 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.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as pimozide, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine may be required. 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.
Butorphanol: (Moderate) Concomitant use of butorphanol with other central nervous system (CNS) depressants, such as pimozide, can potentiate the effects of butorphanol and may lead to additive CNS or respiratory depression. Prior to concurrent use of butorphanol 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. If these agents are used together, a reduced dosage butorphanol may be necessary. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression.
Cabergoline: (Moderate) Cabergoline should not be coadministered with pimozide due to mutually antagonistic effects on dopaminergic function. The dopamine antagonist action of pimozide 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 pimozide.
Cabotegravir; Rilpivirine: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP) and coadministration with other drugs associated with a possible risk for QT prolongation and TdP, such as rilpivirine, should be avoided.
Calcium Phosphate, Supersaturated: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as sodium phosphate, dibasic, sodium phosphate monobasic when used as an enema or bowel cleanser. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and pimozide. CNS depressants can potentiate the effects of cannabidiol.
Capmatinib: (Moderate) Monitor for pimozide-related adverse reactions, including QT prolongation and ventricular arrhythmias, if coadministered with capmatinib. Coadministration may result in elevated pimozide concentrations. Pimozide is metabolized primarily through CYP3A, and to a lesser extent CYP1A2 and CYP2D6; capmatinib is a moderate CYP1A2 inhibitor.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Carbidopa; Levodopa: (Major) Due to opposing effects on central dopaminergic activity, pimozide and levodopa may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to pimozide. 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, pimozide and levodopa may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to pimozide. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Carbinoxamine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Celecoxib: (Moderate) A dosage adjustment may be warranted for pimozide if coadministered with celecoxib due to the potential for celecoxib to enhance the exposure and toxicity of pimozide. Celecoxib is a CYP2D6 inhibitor, and pimozide is a CYP2D6 substrate.
Celecoxib; Tramadol: (Major) Concurrent use of tramadol and pimozide should be avoided if possible. Antipsychotics may enhance the seizure risk of tramadol. Additive CNS depression may also be seen with the concomitant use of tramadol and pimozide. (Moderate) A dosage adjustment may be warranted for pimozide if coadministered with celecoxib due to the potential for celecoxib to enhance the exposure and toxicity of pimozide. Celecoxib is a CYP2D6 inhibitor, and pimozide is a CYP2D6 substrate.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and pimozide. Concurrent use may result in additive CNS depression.
Ceritinib: (Contraindicated) Because of the potential for torsade de pointes, coadministration of pimozide with ceritinib is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Ceritinib also prolongs the QT interval.
Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with pimozide 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 pimozide 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.
Cetrorelix: (Moderate) Drugs that cause hyperprolactinemia, such as pimozide, should not be administered concomitantly with gonadotropin releasing hormone since hyperprolactinemia down-regulates the number of pituitary GnRH receptors.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Chloramphenicol: (Major) Concurrent use of pimozide and chloramphenicol should be avoided. Pimozide is metabolized primarily through CYP3A4, and chloramphenicol is a potent CYP3A4 inhibitor. Elevated pimozide concentrations occurring through inhibition of CYP3A4 can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Chlorcyclizine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Chlordiazepoxide: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including benzodiazepines.
Chlordiazepoxide; Amitriptyline: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including benzodiazepines.
Chlordiazepoxide; Clidinium: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including benzodiazepines.
Chloroquine: (Contraindicated) Coadministration of chloroquine with pimozide is contraindicated due to the increased risk of QT prolongation. 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. Pimozide is associated with a well-established risk of QT prolongation and TdP.
Chlorothiazide: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Chlorpheniramine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as pimozide, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine may be required. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Chlorpheniramine; Dextromethorphan: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of other central nervous system (CNS) depressants, such as pimozide, can potentiate the effects of dihydrocodeine and may lead to additive CNS or respiratory depression, or profound sedation. If these agents are used together, a reduced initial dosage of dihydrocodeine is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include pimozide. (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Chlorpheniramine; Phenylephrine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Chlorpheniramine; Pseudoephedrine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Chlorpromazine: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of pimozide with chlorpromazine is contraindicated. Concurrent use of pimozide with phenothiazines 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. Many phenothiazines are inhibitors of CYP2D6, one of the metabolic pathways of pimozide.
Chlorthalidone: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Chlorthalidone; Clonidine: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment. (Moderate) Disturbances of orthostatic regulation (e.g., orthostatic hypotension, dizziness, fatigue) and additive sedation may be induced or exacerbated in patients receiving concomitant clonidine and antipsychotics. Caution patients to avoid hazardous tasks, such as driving or operating machinery, until the effects of concurrent use are known. Also, based on observations in patients in a state of alcoholic delirium, it has been suggested that 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.
Ciclesonide: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Cimetidine: (Contraindicated) Because post-marketing surveillance reports have documented QT prolongation and ventricular arrhythmias, including torsade de pointes and death when known and potent inhibitors of CYP3A4 are coadministered with pimozide, the use of cimetidine should be considered contraindicated in patients taking pimozide. Pimozide is metabolized primarily through CYP3A4, and to a lesser extent CYP1A2 and CYP2D6. Cimetidine is an inhibitor of CYP3A4, CYP2D6, and CYP1A2. Elevated pimozide concentrations can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Cinacalcet: (Moderate) Monitor for pimozide-related adverse reactions, including QT prolongation and ventricular arrhythmias, if coadministered with cinacalcet. Coadministration may result in elevated pimozide concentrations. Pimozide is metabolized primarily through CYP3A, and to a lesser extent CYP1A2 and CYP2D6; cinacalcet is a moderate CYP2D6 inhibitor.
Ciprofloxacin: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and CYP1A2 is thought to be a minor metabolic route for pimozide. Elevated pimozide plasma concentrations due to impaired CYP1A2 metabolism may result in QT prolongation and ventricular arrhythmias. Therefore, the use of pimozide with potent CYP1A2 inhibitors such as ciprofloxacin should be avoided until more is known about the safety of these combinations. Although less likely than with most quinolones, coadministration of ciprofloxacin with drugs known to prolong the QT interval could increase the risk of developing TdP in predisposed patients. Rare cases of TdP have been reported with ciprofloxacin during post-marketing surveillance.
Cisapride: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of cisapride with pimozide is contraindicated.
Citalopram: (Contraindicated) Pimozide is contraindicated for use with selective serotonin reuptake inhibitors (SSRIs) due to an increased risk of QT prolongation and torsade de pointes (TdP). Pimozide is thought to be primarily metabolized through CYP3A4, and to a lesser extent, CYP1A2 and CYP2D6. Elevated plasma concentrations of pimozide occurring through inhibition of one or more of these isoenzymes by SSRIs can lead to QT prolongation, ventricular arrhythmias, and sudden death. Additionally, most SSRIs are also associated with QT prolongation, further increasing the risk of additive QT prolongation.
Clarithromycin: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of macrolide antibiotics with pimozide is contraindicated.
Clemastine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Clobazam: (Major) A dosage reduction of CYP2D6 substrates, such as pimozide, may be necessary during co-administration of clobazam. Limited in vivo data suggest that clobazam is an inhibitor of CYP2D6. Elevated concentrations of pimozide occurring through inhibition of CYP2D6 may increase the risk of pimozide-related adverse effects, including QT prolongation and torsade de pointes. Antipsychotics may lower the seizure threshold and reduce the effectiveness of clobazam as an anticonvulsant. Additive CNS effects, including somnolence, are also likely to occur.
Clofazimine: (Contraindicated) Avoid concomitant use of clofazimine and pimozide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Clonazepam: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including benzodiazepines.
Clonidine: (Moderate) Disturbances of orthostatic regulation (e.g., orthostatic hypotension, dizziness, fatigue) and additive sedation may be induced or exacerbated in patients receiving concomitant clonidine and antipsychotics. Caution patients to avoid hazardous tasks, such as driving or operating machinery, until the effects of concurrent use are known. Also, based on observations in patients in a state of alcoholic delirium, it has been suggested that 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) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including benzodiazepines.
Clozapine: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of pimozide with clozapine is contraindicated. Concurrent use of pimozide with atypical agents may increase the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Cobicistat: (Contraindicated) Coadministration of pimozide with cobicistat is contraindicated. Cobicistat is a strong inhibitor of CYP3A4 and a CYP2D6 inhibitor; plasma concentrations of drugs extensively metabolized by these enzymes, such as pimozide, are expected to increase with concurrent use. Elevated plasma concentrations of pimozide have been associated with QT prolongation and serious cardiovascular adverse events including death due to torsade de pointes.
Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as pimozide, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine may be required. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as pimozide, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine may be required. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as pimozide, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine may be required. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
Codeine; Phenylephrine; Promethazine: (Contraindicated) Coadministration of promethazine

and pimozide is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Promethazine is also an inhibitor of CYP2D6. Elevated pimozide concentrations occurring through inhibition of CYP3A4, CYP2D6, and/or CYP1A2 can lead to QT prolongation, ventricular arrhythmias, and sudden death. Co-administration of promethazine and antipsychotics may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as pimozide, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine may be required. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
Codeine; Promethazine: (Contraindicated) Coadministration of promethazine and pimozide is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Promethazine is also an inhibitor of CYP2D6. Elevated pimozide concentrations occurring through inhibition of CYP3A4, CYP2D6, and/or CYP1A2 can lead to QT prolongation, ventricular arrhythmias, and sudden death. Co-administration of promethazine and antipsychotics may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as pimozide, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine may be required. 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.
COMT inhibitors: (Major) Due to opposing effects on central dopaminergic activity, pimozide and COMT inhibitors may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic instead of pimozide if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Conivaptan: (Major) Avoid concomitant use of pimozide and conivaptan. Concomitant use may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is CYP3A substrate, and conivaptan is a moderate CYP3A inhibitor.
Corticosteroids: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Cortisone: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Crizotinib: (Contraindicated) Because of the potential for TdP, use of crizotinib with pimozide is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and crizotinib has also been associated with QT prolongation. Additionally, pimozide is a CYP3A4 substrate and crizotinib is a moderate CYP3A4 inhibitor.
Cyproheptadine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Dacomitinib: (Contraindicated) Concurrent use of pimozide and dacomitinib is contraindicated. Coadministration may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is a CYP2D6 substrate and dacomitinib is a strong CYP2D6 inhibitor. Coadministration with another strong CYP2D6 inhibitor increased pimozide exposure by 151%.
Danazol: (Major) Concurrent use of pimozide and danazol should be avoided. Pimozide is metabolized primarily through CYP3A4, and danazol is a CYP3A4 inhibitor. Elevated pimozide concentrations occurring through inhibition of CYP3A4 can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Dantrolene: (Moderate) Simultaneous use of skeletal muscle relaxants and other CNS depressants, such as antipsychotics, can increase CNS depression.
Darifenacin: (Moderate) Caution is advisable during concurrent use of pimozide and moderate CYP2D6 inhibitors such as darifenacin. Pimozide is metabolized primarily through CYP3A4, and to a lesser extent CYP1A2 and CYP2D6. While the manufacturer has provided no guidance regarding pimozide use with mild or moderate CYP2D6 inhibitors, concurrent use of the drug with more potent inhibitors of CYP2D6 is contraindicated. Elevated concentrations of pimozide can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Darunavir; Cobicistat: (Contraindicated) Coadministration of pimozide with cobicistat is contraindicated. Cobicistat is a strong inhibitor of CYP3A4 and a CYP2D6 inhibitor; plasma concentrations of drugs extensively metabolized by these enzymes, such as pimozide, are expected to increase with concurrent use. Elevated plasma concentrations of pimozide have been associated with QT prolongation and serious cardiovascular adverse events including death due to torsade de pointes.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Contraindicated) Coadministration of pimozide with cobicistat is contraindicated. Cobicistat is a strong inhibitor of CYP3A4 and a CYP2D6 inhibitor; plasma concentrations of drugs extensively metabolized by these enzymes, such as pimozide, are expected to increase with concurrent use. Elevated plasma concentrations of pimozide have been associated with QT prolongation and serious cardiovascular adverse events including death due to torsade de pointes.
Dasatinib: (Contraindicated) Coadministration of dasatinib and pimozide is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Pimozide is associated with a well-established risk of QT prolongation and TdP.
Deflazacort: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Degarelix: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of degarelix with pimozide is contraindicated; the efficacy of degarelix may also be reduced. Pimozide is associated with a well-established risk of QT prolongation and TdP. Androgen deprivation therapy (i.e., degarelix) may also prolong the QT/QTc interval. Additionally, pimozide can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; degarelix is a GnRH analog.
Delavirdine: (Contraindicated) Coadministration of pimozide and delavirdine is contraindicated. Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as pimozide, should be expected with concurrent use. Elevated pimozide concentrations can lead to QT prolongation, ventricular arrhythmia, and sudden death.
Deutetrabenazine: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of deutetrabenazine with pimozide is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and TdP. 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. Also, deutetrabenazine is a reversible, dopamine depleting drug and pimozide is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Additive CNS depression may occur during coadministration of pimozide and deutetrabenazine.
Dexamethasone: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Dexchlorpheniramine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Dexmedetomidine: (Contraindicated) Avoid concomitant use of dexmedetomidine and pimozide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Dextromethorphan; Bupropion: (Contraindicated) Coadministration of pimozide and bupropion is contraindicated due to the potential for increased pimozide exposure. Elevated concentrations of pimozide can lead to QT prolongation, ventricular arrhythmias, and sudden death. The risk of seizure may also be increased as both drugs lower the seizure threshold. Bupropion is a strong CYP2D6 inhibitor; pimozide is a CYP2D6 substrate. Coadministration of pimozide with another strong CYP2D6 inhibitor increased the pimozide AUC by 151%.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Dextromethorphan; Quinidine: (Contraindicated) Coadministration of pimozide and quinidine is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Pimozide exposure may also be increased; elevated concentrations of pimozide can lead to QT prolongation, ventricular arrhythmias, and sudden death. Quinidine is a strong CYP2D6 inhibitor that has been associated with QT prolongation and rare cases of TdP. Pimozide is a CYP2D6 substrate that is associated with a well-established risk of QT prolongation and TdP. Coadministration of pimozide with another strong CYP2D6 inhibitor increased the pimozide AUC by 151%.
Diazepam: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including benzodiazepines.
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: (Contraindicated) Concurrent use of pimozide and diltiazem should be avoided. Pimozide is metabolized primarily through CYP3A4, and diltiazem is a CYP3A4 inhibitor. Elevated pimozide concentrations occurring through inhibition of CYP3A4 can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Dimenhydrinate: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Diphenhydramine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Diphenhydramine; Ibuprofen: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Diphenhydramine; Naproxen: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Diphenhydramine; Phenylephrine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Diphenoxylate; Atropine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including diphenoxylate/difenoxin.
Disopyramide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of disopyramide with pimozide is contraindicated.
Disulfiram: (Major) Concurrent use of pimozide with CYP1A2 inhibitors such as disulfiram should be avoided if possible. Pimozide is metabolized primarily through CYP3A4, and to a lesser extent CYP1A2 and CYP2D6. Elevated pimozide concentrations occurring through inhibition of CYP3A4, CYP2D6, and/or CYP1A2 can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Dofetilide: (Contraindicated) Coadministration of pimozide with dofetilide is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Both drugs are associated with a well-established risk of QT prolongation and TdP.
Dolasetron: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of dolasetron with pimozide is contraindicated.
Dolutegravir; Rilpivirine: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP) and coadministration with other drugs associated with a possible risk for QT prolongation and TdP, such as rilpivirine, should be avoided.
Donepezil: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of donepezil with pimozide is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and TdP. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP.
Donepezil; Memantine: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of donepezil with pimozide is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and TdP. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP.
Doxylamine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Doxylamine; Pyridoxine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Dronabinol: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including dronabinol.
Dronedarone: (Contraindicated) Concomitant use of dronedarone and pimozide is contraindicated. Dronedarone is an inhibitor of CYP3A4. Pimozide is a substrate for CYP3A4. Coadministration of dronedarone and pimozide may result in elevated plasma concentrations of pimozide. In addition, pimozide has been established to have a causal association with QT prolongation and Torsade de Pointes (TdP). Dronedarone is associated with dose-related increases in the QTc interval. 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; concomitant use is contraindicated.
Droperidol: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of droperidol with pimozide is contraindicated.
Duloxetine: (Moderate) Caution is advisable during concurrent use of pimozide and moderate CYP2D6 inhibitors such as duloxetine. Pimozide is metabolized primarily through CYP3A4, and to a lesser extent CYP1A2 and CYP2D6. While the manufacturer has provided no guidance regarding pimozide use with mild or moderate CYP2D6 inhibitors, concurrent use of the drug with more potent inhibitors of CYP2D6 is contraindicated. Elevated concentrations of pimozide can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Efavirenz: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Efavirenz has also been associated with QT prolongation. Because of the potential for QT prolongation and TdP, use of efavirenz with pimozide is contraindicated.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Efavirenz has also been associated with QT prolongation. Because of the potential for QT prolongation and TdP, use of efavirenz with pimozide is contraindicated.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Efavirenz has also been associated with QT prolongation. Because of the potential for QT prolongation and TdP, use of efavirenz with pimozide is contraindicated.
Elbasvir; Grazoprevir: (Major) Administering pimozide with grazoprevir may result in elevated pimozide plasma concentrations. Pimozide is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Elexacaftor; tezacaftor; ivacaftor: (Minor) Use caution when administering ivacaftor and pimozide concurrently. Ivacaftor is an inhibitor of CYP3A and pimozide is partially metabolized by CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as pimozide, can theoretically increase pimozide exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
Eliglustat: (Contraindicated) Coadministration of pimozide and eliglustat is contraindicated. Pimozide is a CYP2D6 substrate associated with a well-established risk of QT prolongation and torsade de pointes (TdP); its use is contraindicated with other drugs that prolong the QT interval and drugs that are strong CYP2D6 inhibitors. Eliglustat is a CYP2D6 inhibitor that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration of pimozide and eliglustat may result in additive effects on the QT interval and, potentially, increased plasma concentrations pimozide, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias).
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) Coadministration of pimozide with cobicistat is contraindicated. Cobicistat is a strong inhibitor of CYP3A4 and a CYP2D6 inhibitor; plasma concentrations of drugs extensively metabolized by these enzymes, such as pimozide, are expected to increase with concurrent use. Elevated plasma concentrations of pimozide have been associated with QT prolongation and serious cardiovascular adverse events including death due to torsade de pointes.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Coadministration of pimozide with cobicistat is contraindicated. Cobicistat is a strong inhibitor of CYP3A4 and a CYP2D6 inhibitor; plasma concentrations of drugs extensively metabolized by these enzymes, such as pimozide, are expected to increase with concurrent use. Elevated plasma concentrations of pimozide have been associated with QT prolongation and serious cardiovascular adverse events including death due to torsade de pointes.
Emapalumab: (Moderate) Monitor for decreased efficacy of pimozide and adjust the dose as needed during coadministration with emapalumab. Pimozide is a CYP3A4 and CYP2D6 substrate with a narrow therapeutic range. Emapalumab may normalize CYP450 activity, which may decrease the efficacy of drugs that are CYP450 substrates due to increased metabolism.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP) and coadministration with other drugs associated with a possible risk for QT prolongation and TdP, such as rilpivirine, should be avoided.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP) and coadministration with other drugs associated with a possible risk for QT prolongation and TdP, such as rilpivirine, should be avoided.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Encorafenib: (Contraindicated) Coadministration of encorafenib with pimozide is contraindicated due to the potential for QT prolongation. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
Entrectinib: (Contraindicated) Coadministration of pimozide with entrectinib is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Pimozide is associated with a well-established risk of QT prolongation and TdP. Entrectinib has been associated with QT prolongation.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Eribulin: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of eribulin with pimozide is contraindicated.
Erythromycin: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of macrolide antibiotics with pimozide is contraindicated.
Escitalopram: (Contraindicated) Pimozide is contraindicated for use with selective serotonin reuptake inhibitors (SSRIs) due to an increased risk of QT prolongation and torsade de pointes (TdP). Pimozide is thought to be primarily metabolized through CYP3A4, and to a lesser extent, CYP1A2 and CYP2D6. Elevated plasma concentrations of pimozide occurring through inhibition of one or more of these isoenzymes by SSRIs can lead to QT prolongation, ventricular arrhythmias, and sudden death. Additionally, most SSRIs are also associated with QT prolongation, further increasing the risk of additive QT prolongation.
Esketamine: (Major) Closely monitor patients receiving esketamine and pimozide 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.
Estazolam: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including benzodiazepines.
Eszopiclone: (Moderate) A reduction in the dose of eszopiclone should be considered during co-administration of other CNS depressants, such as antipsychotics like pimozide, to minimize additive sedative effects. In addition, the risk of next-day psychomotor impairment is increased during co-administration of eszopiclone and other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving. Antipsychotics with a higher incidence of sedation, such as olanzapine, clozapine, quetiapine, lurasidone, chlorpromazine, and thioridazine, are more likely to interact with eszopiclone. In one evaluation, concurrent use of eszopiclone and olanzapine reduced psychomotor function as measured by the Digit Symbol Substitution Test (DSST).
Ethacrynic Acid: (Moderate) Caution is advisable during concurrent use of pimozide and loop diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Ethosuximide: (Moderate) Concomitant use of ethosuximide with pimozide can lower the seizure threshold and reduce the effectiveness of ethosuximide as an anticonvulsant. Additive CNS effects, such as drowsiness, may also occur.
Everolimus: (Major) Concurrent use of pimozide and everolimus should be avoided. Coadministration may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is metabolized primarily through CYP3A4, and to a lesser extent CYP1A2 and CYP2D6. Everolimus is a competitive CYP2D6 inhibitor and a weak CYP3A4 inhibitor.
Fedratinib: (Major) Concurrent use of pimozide and fedratinib should be avoided. Pimozide is metabolized primarily through CYP3A4, and fedratinib is a CYP3A4 inhibitor. Elevated pimozide concentrations occurring through inhibition of CYP3A4 can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and pimozide. Concurrent use may result in additive CNS depression.
Fentanyl: (Moderate) Concomitant use of fentanyl with other central nervous system (CNS) depressants, such as pimozide, 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 pimozide may be required. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
Fingolimod: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of fingolimod with pimozide is contraindicated.
Flecainide: (Contraindicated) Avoid concomitant use of pimozide and flecainide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Fluconazole: (Contraindicated) Concurrent use of fluconazole and pimozide is contraindicated. Fluconazole has been associated with QT prolongation and pimozide has been specifically established to have a causal association with QT prolongation and torsade de pointes (TdP). Additionaly, fluconazole inhibits CYP3A4 and concomitant use of pimozide with CYP3A4 inhibitors is contraindicated; rare cases of QT prolongation, ventricular arrhythmia and sudden death have occured during coadministration of pimozide with CYP3A4 inhibitor.
Fludrocortisone: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Flunisolide: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Fluoxetine: (Contraindicated) Pimozide is contraindicated for use with selective serotonin reuptake inhibitors (SSRIs) due to an increased risk of QT prolongation and torsade de pointes (TdP). Pimozide is thought to be primarily metabolized through CYP3A4, and to a lesser extent, CYP1A2 and CYP2D6. Elevated plasma concentrations of pimozide occurring through inhibition of one or more of these isoenzymes by SSRIs can lead to QT prolongation, ventricular arrhythmias, and sudden death. Additionally, most SSRIs are also associated with QT prolongation, further increasing the risk of additive QT prolongation.
Fluphenazine: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of pimozide with fluphenazine is contraindicated. Concurrent use of pimozide with phenothiazines 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. Many phenothiazines are inhibitors of CYP2D6, one of the metabolic pathways of pimozide.
Flurazepam: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including benzodiazepines.
Fluticasone: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Fluticasone; Salmeterol: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Fluticasone; Vilanterol: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Fluvoxamine: (Contraindicated) Pimozide is contraindicated for use with selective serotonin reuptake inhibitors (SSRIs) due to an increased risk of QT prolongation and torsade de pointes (TdP). Pimozide is thought to be primarily metabolized through CYP3A4, and to a lesser extent, CYP1A2 and CYP2D6. Elevated plasma concentrations of pimozide occurring through inhibition of one or more of these isoenzymes by SSRIs can lead to QT prolongation, ventricular arrhythmias, and sudden death. Additionally, most SSRIs are also associated with QT prolongation, further increasing the risk of additive QT prolongation.
Food: (Moderate) The use of Areca Nut (Betel Nut) with pimozide is not recommended. Concurrent use of pimozide and betel nut, may result in an increased risk of extrapyramidal symptoms (EPS). Monitor closely for EPS if this combination is used. Case reports have documented an increase in EPS when betel nut was chewed by patients taking phenothiazine antipsychotics for schizophrenia. Use of an anticholinergic agent did not improve the extrapyramidal effects, but the symptoms resolved when the betel nut was discontinued. A similar interaction can be expected to occur when betel nut is used with other antipsychotics, including pimozide. Case reports suggest the onset of these effects occur within 2 weeks, and that resolution occurs within 4 to 7 days after discontinuation of betel nut. The cholinergic activity of betel nut has been attributed to the arecoline content of the herb.
Formoterol; Mometasone: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Foscarnet: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of foscarnet with pimozide is contraindicated.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Fostamatinib: (Major) Avoid concurrent use of pimozide and fostamatinib. Elevated pimozide concentrations occurring through inhibition of CYP3A4 can lead to QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is metabolized primarily through CYP3A4 and fostamatinib is a weak CYP3A4 inhibitor.
Fostemsavir: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of fostemsavir with pimozide is contraindicated. 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 pimozide and loop diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and pimozide. Concomitant use of gabapentin with pimozide 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 down-regulates the number of pituitary GnRH receptors.
Gefitinib: (Moderate) Monitor for an increase in pimozide-related adverse reactions if coadministration with gefitinib is necessary. Pimozide is a CYP2D6 substrate with a narrow therapeutic range and gefitinib is a CYP2D6 inhibitor. While the manufacturer has provided no guidance regarding pimozide use with mild or moderate CYP2D6 inhibitors, concurrent use of the drug with more potent inhibitors of CYP2D6 is contraindicated. Elevated concentrations of pimozide can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Gemifloxacin: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of gemifloxacin with pimozide is contraindicated.
Gemtuzumab Ozogamicin: (Contraindicated) Coadministration of gemtuzumab ozogamicin with pimozide is contraindicated due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Pimozide is associated with a well-established risk of QT prolongation and TdP.
Gilteritinib: (Contraindicated) Use of gilteritinib with pimozide is contraindicated because of the potential for torsade de pointes (TdP). Gilteritinib has been associated with QT prolongation. Pimozide is associated with a well-established risk of QT prolongation and TdP.
Givosiran: (Major) Avoid concomitant use of givosiran and pimozide due to the risk of increased pimozide-related adverse reactions. If use is necessary, consider decreasing the pimozide dose. Pimozide is a CYP2D6 substrate. Givosiran may moderately reduce hepatic CYP2D6 enzyme activity because of its pharmacological effects on the hepatic heme biosynthesis pathway.
Glasdegib: (Contraindicated) Coadministration of glasdegib and pimozide is contraindicated due to the potential for additive QT prolongation and torsade de pointes (TdP). Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
Goserelin: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of goserelin with pimozide is contraindicated; the efficacy of goserelin may also be reduced. Pimozide is associated with a well-established risk of QT prolongation and TdP. Androgen deprivation therapy (i.e., goserelin) may also prolong the QT/QTc interval. Pimozide can also cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; goserelin is a GnRH analog.
Granisetron: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of granisetron with pimozide is contraindicated.
Grapefruit juice: (Contraindicated) Patients should be advised to avoid grapefruit juice products while taking pimozide due to the possibility of pimozide toxicity. Grapefruit juice inhibits the cytochrome P-450 3A4 isozyme in the gut wall. Grapefruit juice contains furanocoumarins that are metabolized by CYP3A4 to reactive intermediates. These intermediates form a covalent bond to the active site of the CYP3A4 enzyme, causing irreversible inactivation (mechanism-based inhibition). Consequently, CYP3A4 activity in the gut wall is inhibited until de novo synthesis returns the enzyme to its previous level. Therefore, grapefruit juice may inhibit the metabolism of pimozide by CYP3A4, resulting in possible QT prolongation and torsade de pointes (TdP).
Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include pimozide.
Guselkumab: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with CYP2D6 substrates that have a narrow therapeutic index, such as pimozide. Monitor pimozide concentrations if guselkumab is initiated or discontinued; pimozide dose adjustments may be needed. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Haloperidol: (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.
Histrelin: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of histrelin with pimozide is contraindicated; the efficacy of histrelin may also be reduced. Pimozide is associated with a well-established risk of QT prolongation and TdP. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval. Pimozide can also cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog.
Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include pimozide.
Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include pimozide.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include pimozide.
Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include pimozide.
Hydrocortisone: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
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 pimozide. 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: (Contraindicated) Avoid concomitant use of pimozide and hydroxychloroquine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Hydroxyzine: (Contraindicated) Avoid concomitant use of pimozide and hydroxyzine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Ibuprofen; Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as pimozide, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking pimozide, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider using a lower pimozide dose. Monitor patients for sedation and respiratory depression.
Ibutilide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of ibutilide with pimozide is contraindicated.
Idelalisib: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with pimozide, a CYP3A substrate, as pimozide toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Iloperidone: (Contraindicated) Iloperidone has a risk of QT prolongation and is contraindicated with pimozide. Concurrent use of pimozide with atypical agents may increase the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Imatinib: (Contraindicated) Concurrent use of pimozide and imatinib, STI-571 should be avoided. Pimozide is metabolized primarily through CYP3A4, and to a lesser extent CYP1A2 and CYP2D6. Imatinib, STI-571 is an inhibitor of CYP3A4 and CYP2D6. Elevated pimozide concentrations occurring through inhibition of CYP3A4, CYP2D6, and/or CYP1A2 can lead to QT prolongation, ventricular arrhythmias, and sudden death. Concurrent use of CYP3A4 inhibitors or potent CYP2D6 inhibitors and pimozide is contraindicated by the manufacturer of pimozide.
Inotuzumab Ozogamicin: (Contraindicated) Coadministration of inotuzumab ozogamicin with pimozide is contraindicated due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). Pimozide is associated with a well-established risk of QT prolongation and TdP. Inotuzumab has also been associated with QT interval prolongation.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Isavuconazonium: (Major) Concomitant use of isavuconazonium with pimozide should be avoided. Pimozide is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Elevated pimozide concentrations occurring through inhibition of CYP3A4 can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Isoflurane: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of isoflurane with pimozide is contraindicated.
Istradefylline: (Moderate) Monitor for pimozide-related adverse reactions if coadministration of istradefylline 40 mg daily is necessary. Pimozide is a CYP3A4 substrate; istradefylline administered as 40 mg daily is a weak CYP3A4 inhibitor. There was no effect on drug exposure when istradefylline 20 mg daily was coadministered with a sensitive CYP3A4 substrate.
Itraconazole: (Contraindicated) Pimozide is contraindicated for use during and for 2 weeks after itraconazole therapy. Serious cardiovascular events including EKG changes (i.e., QT prolongation), cardiac arrhythmias, including ventricular arrhythmias and torsade de pointes, cardiac arrest, and sudden death have occurred when these drugs were administered together. Itraconazole is an inhibitor of CYP3A4, which may cause increased plasma concentrations of pimozide resulting in potentially serious and life threatening side effects.
Ivacaftor: (Minor) Use caution when administering ivacaftor and pimozide concurrently. Ivacaftor is an inhibitor of CYP3A and pimozide is partially metabolized by CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as pimozide, can theoretically increase pimozide exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
Ivosidenib: (Contraindicated) Coadministration of ivosidenib with pimozide is contraindicated due to an increased risk of QT prolongation. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and pimozide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use may also increase the exposure of pimozide, further increasing the risk for adverse effects. Pimozide is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor.
Lansoprazole; Amoxicillin; Clarithromycin: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of macrolide antibiotics with pimozide is contraindicated.
Lapatinib: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of lapatinib with pimozide is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and TdP. Lapatinib has also been associated with concentration-dependent QT prolongation; ventricular arrhythmias and TdP have been reported in postmarketing experience with lapatinib.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and pimozide. Concurrent use may result in additive CNS depression.
Lefamulin: (Contraindicated) Coadministration of pimozide with lefamulin is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Pimozide is associated with a well-established risk of QT prolongation and TdP. 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.
ong>Lenacapavir: (Major) Avoid concomitant use of pimozide and lenacapavir. Concomitant use may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is CYP3A substrate, and lenacapavir is a moderate CYP3A inhibitor.
Leniolisib: (Moderate) Monitor for pimozide-related adverse reactions, including QT prolongation and ventricular arrhythmias, if coadministered with leniolisib. Coadministration may result in elevated pimozide concentrations. Pimozide is metabolized primarily through CYP3A, and to a lesser extent CYP1A2 and CYP2D6; leniolisib is a weak CYP1A2 inhibitor.
Lenvatinib: (Contraindicated) Because of the potential for torsades de pointes (TdP), use of pimozide with lenvatinib is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Prolongation of the QT interval has been reported with lenvatinib therapy.
Letermovir: (Contraindicated) Concurrent administration of letermovir and pimozide is contraindicated. Taking these drugs together may result in increased concentrations of pimozide due to inhibition of CYP3A4 by letermovir, which could lead to QT prolongation and torsade de pointes.
Leuprolide: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of leuprolide with pimozide is contraindicated; the efficacy of leuprolide may also be reduced. Pimozide is associated with a well-established risk of QT prolongation and TdP. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval. Pimozide can also cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Leuprolide; Norethindrone: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of leuprolide with pimozide is contraindicated; the efficacy of leuprolide may also be reduced. Pimozide is associated with a well-established risk of QT prolongation and TdP. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval. Pimozide can also cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with pimozide 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, pimozide and levodopa may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to pimozide. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Levofloxacin: (Contraindicated) Avoid concomitant use of pimozide and levofloxacin due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and pimozide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use may also increase the exposure of pimozide, further increasing the risk for adverse effects. Pimozide is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor.
Levorphanol: (Moderate) Concomitant use of levorphanol with other CNS depressants such as pimozide 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.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Lithium: (Contraindicated) Lithium has been associated with QT prolongation. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of lithium with pimozide is contraindicated. Additionally, some atypical antipsychotics are considered first-line adjunctive therapy to mood stabilizers such as lithium. However, it is advisable to monitor patients for neurotoxicity during co-administration. Neuroleptic malignant syndrome (NMS) has been observed occasionally during concurrent use of lithium and either atypical or conventional antipsychotics. Additive extrapyramidal effects have also been noted. 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., aripiprazole, 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: (Contraindicated) Concomitant use of lofexidine and pimozide is contraindicated due to the potential for additive QT prolongation and torsade de pointes (TdP). Lofexidine may prolong the QT interval, and TdP has been reported during postmarketing use. Pimozide is associated with a well-established risk of QT prolongation and TdP.
Lonafarnib: (Contraindicated) Concurrent use of pimozide and lonafarnib is contraindicated. Coadministration may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is metabolized primarily through CYP3A4, and lonafarnib is a strong CYP3A4 inhibitor.
Loop diuretics: (Moderate) Caution is advisable during concurrent use of pimozide and loop diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Loperamide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because high doses of loperamide have been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest, coadministration is contraindicated.
Loperamide; Simethicone: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because high doses of loperamide have been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest, coadministration is contraindicated.
Lorazepam: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including benzodiazepines.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Loxapine: (Major) Concurrent use of pimozide with loxapine may increase the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, extrapyramidal symptoms, or seizures.
Lumacaftor; Ivacaftor: (Minor) Use caution when administering ivacaftor and pimozide concurrently. Ivacaftor is an inhibitor of CYP3A and pimozide is partially metabolized by CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as pimozide, can theoretically increase pimozide exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
Lumateperone: (Moderate) Coadministration of antipsychotics, such as lumateperone and pimozide, 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. 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: (Contraindicated) Because of the potential for TdP, use of macimorelin with pimozide is contraindicated. Before administering macimorelin, discontinue use of pimozide and allow a sufficient washout period to pass. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval.
Macrolides: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of macrolide antibiotics with pimozide is contraindicated.
Magnesium Citrate: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as magnesium citrate when used to cleanse the bowel, except when medically necessary. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia.
Maprotiline: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of maprotiline with pimozide is contraindicated.
Maribavir: (Major) Avoid concomitant use of pimozide and maribavir. Concomitant use may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is CYP3A substrate and maribavir is a weak CYP3A inhibitor.
Meclizine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Mefloquine: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of mefloquine with pimozide is contraindicated.
Meperidine: (Moderate) Concomitant use of other central nervous system (CNS) depressants, such as pimozide, can potentiate the effects of meperidine and may lead to additive CNS or respiratory depression, hypotension, or profound sedation. If these agents are used together, a reduced initial dosage of meperidine 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.
Meprobamate: (Moderate) The CNS-depressant effects of both meprobamate and pimozide can be potentiated with concomitant administration.
Methadone: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of methadone with pimozide is contraindicated.
Methazolamide: (Moderate) Caution is advisable during concurrent use of pimozide and methazolamide as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Methyclothiazide: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Methylphenidate Derivatives: (Major) Pimozide should not be used in patients taking medicines that may, themselves, cause motor and phonic tics (e.g., methylphenidate) until such patients have been withdrawn from these drugs to determine whether or not the drugs, rather than Tourette's Disorder, are responsible for the tics. Once this issue is excluded, use together may proceed with caution.
Methylprednisolone: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Metoclopramide: (Contraindicated) Avoid metoclopramide in patients receiving pimozide. 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 pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Metreleptin: (Moderate) Carefully consider the risks and benefits of coadministration before giving metreleptin and pimozide concomitantly. Leptin is a cytokine and may have the potential to alter the formation of cytochrome P450 (CYP450) enzymes. The effect of metreleptin on CYP450 enzymes may be clinically relevant for CYP450 substrates with a narrow therapeutic index, such as pimozide. Upon initiation or discontinuation of metreleptin, therapeutic or drug concentration monitoring should be performed if possible, and the dosage of pimozide adjusted as needed.
Metronidazole: (Contraindicated) Avoid concomitant use of metronidazole and pimozide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Metyrapone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as pimozide, should be used with caution. Additive drowsiness and/or dizziness is possible.
Mexiletine: (Major) Concurrent use of pimozide with CYP1A2 inhibitors such as mexiletine should be avoided if possible. Pimozide is metabolized primarily through CYP3A4, and to a lesser extent CYP1A2 and CYP2D6. Elevated pimozide concentrations occurring through inhibition of CYP3A4, CYP2D6, and/or CYP1A2 can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Midazolam: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including benzodiazepines.
Midostaurin: (Contraindicated) Because of the potential for TdP, use of midostaurin with pimozide is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin.
Mifepristone: (Contraindicated) Avoid concomitant use of pimozide and mifepristone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Mirabegron: (Moderate) Caution is advisable during concurrent use of pimozide and moderate CYP2D6 inhibitors such as mirabegron. Pimozide is metabolized primarily through CYP3A4, and to a lesser extent CYP1A2 and CYP2D6. While the manufacturer has provided no guidance regarding pimozide use with mild or moderate CYP2D6 inhibitors, concurrent use of the drug with more potent inhibitors of CYP2D6 is contraindicated. Elevated concentrations of pimozide can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Mirtazapine: (Contraindicated) Avoid concomitant use of pimozide and mirtazapine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Mobocertinib: (Contraindicated) Avoid concomitant use of mobocertinib and pimozide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Molindone: (Major) Concurrent use of pimozide with molindone may increase the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, extrapyramidal symptoms, or seizures.
Mometasone: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
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 pimozide. 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 pimozide. 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: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of moxifloxacin with pimozide is contraindicated.
Nabilone: (Moderate) Concomitant use of nabilone with other CNS depressants like pimozide can potentiate the effects of nabilone on respiratory depression.
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 central nervous system (CNS) depressants, such as pimozide, can potentiate the effects of nalbuphine and may lead to additive CNS or respiratory depression. Prior to concurrent use of nalbuphine 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. If these agents are used together, a reduced dosage nalbuphine and/or pimozide may be necessary. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression.
Nebivolol: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with pimozide. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as pimozide, 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) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with pimozide. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as pimozide, 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: (Contraindicated) Nefazodone inhibits the hepatic CYP3A4 isoenzyme. Post-marketing surveillance reports have documented QT prolongation and ventricular arrhythmias, including torsade de pointes and death, when known and potent inhibitors of CYP3A4 are coadministered with pimozide. Because of the potential severity of these drug interactions, nefazodone is contraindicated for use with these medications.
Netupitant, Fosnetupitant; Palonosetron: (Major) Netupitant is a moderate inhibitor of CYP3A4 and should be used with caution in patients receiving concomitant medications that are primarily metabolized through CYP3A4, such as pimozide. The plasma concentrations of pimozide can increase when co-administered with netupitant; the inhibitory effect on CYP3A4 can last for multiple days, and this might raise the risk for QT prolongation and other side effects from pimozide.
Nicardipine: (Major) Avoid coadministration of pimozide and nicardipine due to the potential for elevated pimozide concentrations that can lead to QT prolongation, ventricular arrhythmia, and sudden death. Pimozide is primarily metabolized through CYP3A4, and to a lesser extent, CYP2D6. Nicardipine is an inhibitor of CYP2D6 and CYP3A4.
Nilotinib: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of nilotinib with pimozide is contraindicated.
Niraparib; Abiraterone: (Moderate) Caution is advisable during concurrent use of pimozide and moderate CYP2D6 inhibitors such as abiraterone. Pimozide is metabolized primarily through CYP3A4, and to a lesser extent CYP1A2 and CYP2D6. While the manufacturer has provided no guidance regarding pimozide use with mild or moderate CYP2D6 inhibitors, concurrent use of the drug with more potent inhibitors of CYP2D6 is contraindicated. Elevated concentrations of pimozide can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Nirmatrelvir; Ritonavir: (Contraindicated) Concomitant use of ritonavir-boosted nirmatrelvir and pimozide is contraindicated; consider an alternative COVID-19 therapy. Coadministration may increase pimozide exposure resulting in increased toxicity. Pimozide is a CYP3A substrate and nirmatrelvir is a CYP3A inhibitor.
Non-Ionic Contrast Media: (Major) Pimozide 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.
Obeticholic Acid: (Moderate) Monitor for pimozide-related adverse reactions, including QT prolongation and ventricular arrhythmias, if coadministered with obeticholic acid. Coadministration may result in elevated pimozide concentrations. Pimozide is metabolized primarily through CYP3A, and to a lesser extent CYP1A2 and CYP2D6; obeticholic acid is a weak CYP1A2 inhibitor.
Ofloxacin: (Contraindicated) Avoid concomitant use of pimozide and ofloxacin due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Olanzapine: (Contraindicated) Olanzapine has a risk of QT prolongation and is contraindicated with pimozide. Concurrent use of pimozide with atypical agents may increase the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Olanzapine; Fluoxetine: (Contraindicated) Olanzapine has a risk of QT prolongation and is contraindicated with pimozide. Concurrent use of pimozide with atypical agents may increase the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. (Contraindicated) Pimozide is contraindicated for use with selective serotonin reuptake inhibitors (SSRIs) due to an increased risk of QT prolongation and torsade de pointes (TdP). Pimozide is thought to be primarily metabolized through CYP3A4, and to a lesser extent, CYP1A2 and CYP2D6. Elevated plasma concentrations of pimozide occurring through inhibition of one or more of these isoenzymes by SSRIs can lead to QT prolongation, ventricular arrhythmias, and sudden death. Additionally, most SSRIs are also associated with QT prolongation, further increasing the risk of additive QT prolongation.
Olanzapine; Samidorphan: (Contraindicated) Olanzapine has a risk of QT prolongation and is contraindicated with pimozide. Concurrent use of pimozide with atypical agents may increase the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Oliceridine: (Major) Concomitant use of oliceridine with pimozide may cause excessive sedation and somnolence. Limit the use of oliceridine with pimozide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Olopatadine; Mometasone: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Ondansetron: (Contraindicated) Avoid concomitant use of pimozide and ondansetron due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. 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.
Osilodrostat: (Contraindicated) Coadministration of pimozide with osilodrostat is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Pimozide is associated with a well-established risk of QT prolongation and TdP. Osilodrostat is associated with dose-dependent QT prolongation.
Osimertinib: (Contraindicated) Concomitant use of osimertinib and pimozide is contraindicated because there is an increased risk of QT prolongation and torsade de pointes (TdP). Pimozide is associated with a well-established risk of QT prolongation and TdP. Osimertinib causes concentration dependent prolongation of the QT interval at recommended dosing.
Oxaliplatin: (Contraindicated) Concomitant use of oxaliplatin and pimozide is contraindicated because there is an increased risk of QT prolongation and torsade de pointes. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). QT prolongation and ventricular arrhythmias including fatal torsade de pointes (TdP) have also been reported with oxaliplatin use in post-marketing experience. Additive QT prolongation is possible.
Oxazepam: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including benzodiazepines.
Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as pimozide, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking pimozide, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider using a lower pimozide dose. Monitor patients for sedation and respiratory depression.
Oxymorphone: (Moderate) Concomitant use of oxymorphone with other CNS depressants may produce additive CNS depressant effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur; examples of other CNS depressants include pimozide. 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: (Contraindicated) Coadministration of pimozide with ozanimod is contraindicated due to the risk for additive QT prolongation and torsade de pointes (TdP). Pimozide is associated with a well-established risk of QT prolongation and TdP. 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.
Pacritinib: (Contraindicated) Avoid concomitant use of pimozide and pacritinib due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use may also increase pimozide exposure and the risk for other pimozide-related adverse effects. Pimozide is a CYP3A and CYP1A2 substrate; pazopanib is a weak CYP3A and CYP1A2 inhibitor.
Palbociclib: (Major) Monitor for an increase in pimozide-related adverse reactions if coadministration with palbociclib is necessary. The dose of pimozide may need to be reduced. Palbociclib is a weak time-dependent inhibitor of CYP3A while pimozide is a CYP3A4 substrate with a narrow therapeutic index.
Paliperidone: (Contraindicated) Pimozide is an antipsychotic with a well-established risk of QT prolongation and torsade te pointes (TdP). Because of the potential for TdP, coadministration with paliperidone is contraindicated. Paliperidone has been associated with QT prolongation; 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 drugs having an association with QT prolongation. Concurrent use of antipsychotics may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, 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: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of pimozide with panobinostat is contraindicated. QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Pimozide is associated with a well-established risk of QT prolongation and TdP.
Paroxetine: (Contraindicated) Pimozide is contraindicated for use with selective serotonin reuptake inhibitors (SSRIs) due to an increased risk of QT prolongation and torsade de pointes (TdP). Pimozide is thought to be primarily metabolized through CYP3A4, and to a lesser extent, CYP1A2 and CYP2D6. Elevated plasma concentrations of pimozide occurring through inhibition of one or more of these isoenzymes by SSRIs can lead to QT prolongation, ventricular arrhythmias, and sudden death. Additionally, most SSRIs are also associated with QT prolongation, further increasing the risk of additive QT prolongation.
Pasireotide: (Contraindicated) Because of the potential for torsades de pointes (TdP), use of pasireotide and pimozide is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Coadministration of pasireotide and drugs that prolong the QT interval may have additive effects on the prolongation of the QT interval.
Pazopanib: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of pazopanib with pimozide is contraindicated.
Pentamidine: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of pentamidine with pimozide is contraindicated.
Pentazocine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as pimozide, can potentiate the effects of pentazocine and may lead to additive CNS or respiratory depression, profound sedation, or coma. If these agents are used together, a reduced dosage of pentazocine may be required. 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.
Pentazocine; Naloxone: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as pimozide, can potentiate the effects of pentazocine and may lead to additive CNS or respiratory depression, profound sedation, or coma. If these agents are used together, a reduced dosage of pentazocine may be required. 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.
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 pimozide.
Perphenazine: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of pimozide with perphenazine is contraindicated. Concurrent use of pimozide with phenothiazines 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. Many phenothiazines are inhibitors of CYP2D6, one of the metabolic pathways of pimozide.
Perphenazine; Amitriptyline: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of pimozide with perphenazine is contraindicated. Concurrent use of pimozide with phenothiazines 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. Many phenothiazines are inhibitors of CYP2D6, one of the metabolic pathways of pimozide.
Pimavanserin: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because pimavanserin causes QT prolonging effects that may be additive to those of pimozide, coadministration is contraindicated.
Pirtobrutinib: (Major) Avoid concomitant use of pimozide and pirtobrutinib. Concomitant use may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is CYP3A substrate, and pirtobrutinib is a weak CYP3A inhibitor.
Pitolisant: (Contraindicated) Coadministration of pimozide with pitolisant is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Pimozide is associated with a well-established risk of QT prolongation and TdP. Pitolisant prolongs the QT interval.
Polyethylene Glycol: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as polyethylene glycol used in colon-cleansing regimens, except when indicated. Use in patients using small doses of polyethylene glycol 3350 (e.g., Miralax) may be permissable, as long as not excessive. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia.
Polyethylene Glycol; Electrolytes: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as polyethylene glycol used in colon-cleansing regimens, except when indicated. Use in patients using small doses of polyethylene glycol 3350 (e.g., Miralax) may be permissable, as long as not excessive. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia.
Polyethylene Glycol; Electrolytes; Ascorbic Acid: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as polyethylene glycol used in colon-cleansing regimens, except when indicated. Use in patients using small doses of polyethylene glycol 3350 (e.g., Miralax) may be permissable, as long as not excessive. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia.
Polyethylene Glycol; Electrolytes; Bisacodyl: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as polyethylene glycol used in colon-cleansing regimens, except when indicated. Use in patients using small doses of polyethylene glycol 3350 (e.g., Miralax) may be permissable, as long as not excessive. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia.
Ponesimod: (Contraindicated) Coadministration of pimozide with ponesimod is contraindicated due to the risk for additive QT prolongation and torsade de pointes (TdP). Pimozide is associated with a well-established risk of QT prolongation and TdP. 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.
Posaconazole: (Contraindicated) Posaconazole is an inhibitor of CYP3A4. Coadministration of posaconazole with drugs metabolized by 3A4, such as pimozide, may result in increased plasma concentrations of these drugs due to decreased metabolism. Increased plasma concentrations of these agents may result in QT prolongation and rare occurrences of torsade de pointes. Concomitant therapy of pimozide and posaconazole is contraindicated.
Pramipexole: (Major) Due to opposing effects on central dopaminergic activity, pimozide and pramipexole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to pimozide. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. In addition, coadministration may result in additive sedation.
Prednisolone: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Prednisone: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Pregabalin: (Moderate) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and pimozide. Concomitant use of pregabalin with pimozide may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
Primaquine: (Contraindicated) Primaquine has the potential to prolong the QT interval. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of primaquine with pimozide is contraindicated.
Procainamide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of procainamide with pimozide is contraindicated.
Prochlorperazine: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of pimozide with prochlorperazine is contraindicated. Concurrent use of pimozide with phenothiazines 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. Many phenothiazines are inhibitors of CYP2D6, one of the metabolic pathways of pimozide.
Promethazine: (Contraindicated) Coadministration of promethazine and pimozide is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Promethazine is also an inhibitor of CYP2D6. Elevated pimozide concentrations occurring through inhibition of CYP3A4, CYP2D6, and/or CYP1A2 can lead to QT prolongation, ventricular arrhythmias, and sudden death. Co-administration of promethazine and antipsychotics may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures.
Promethazine; Dextromethorphan: (Contraindicated) Coadministration of promethazine and pimozide is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Promethazine is also an inhibitor of CYP2D6. Elevated pimozide concentrations occurring through inhibition of CYP3A4, CYP2D6, and/or CYP1A2 can lead to QT prolongation, ventricular arrhythmias, and sudden death. Co-administration of promethazine and antipsychotics may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures.
Promethazine; Phenylephrine: (Contraindicated) Coadministration of promethazine and pimozide is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Promethazine is also an inhibitor of CYP2D6. Elevated pimozide concentrations occurring through inhibition of CYP3A4, CYP2D6, and/or CYP1A2 can lead to QT prolongation, ventricular arrhythmias, and sudden death. Co-administration of promethazine and antipsychotics may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures.
Propafenone: (Contraindicated) Avoid concomitant use of propafenone and pimozide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Protease inhibitors: (Contraindicated) Coadministration of pimozide with protease inhibitors is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Pimozide is thought to be metabolized through CYP3A4, and to a lesser extent CYP1A2 and CYP2D6. Elevated pimozide plasma levels are probable when coadministered with CYP450 inhibitors, such as the protease inhibitors. Increased plasma concentrations of pimozide have been associated with QT prolongation and serious cardiovascular adverse events including death due to TdP.
Pseudoephedrine; Triprolidine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Quazepam: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including benzodiazepines.
Quetiapine: (Contraindicated) Quetiapine has a risk of QT prolongation and is contraindicated with pimozide. Concurrent use of pimozide with atypical agents may increase the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Quinidine: (Contraindicated) Coadministration of pimozide and quinidine is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Pimozide exposure may also be increased; elevated concentrations of pimozide can lead to QT prolongation, ventricular arrhythmias, and sudden death. Quinidine is a strong CYP2D6 inhibitor that has been associated with QT prolongation and rare cases of TdP. Pimozide is a CYP2D6 substrate that is associated with a well-established risk of QT prolongation and TdP. Coadministration of pimozide with another strong CYP2D6 inhibitor increased the pimozide AUC by 151%.
Quinine: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of pimozide with other QT prolonging drugs, such as quinine, is contraindicated. In addition, pimozide is metabolized primarily through CYP3A4, and to a lesser extent CYP1A2 and CYP2D6. Quinine is an inhibitor of CYP3A4 and CYP2D6. Elevated pimozide concentrations occurring through inhibition of CYP3A4, CYP2D6, and/or CYP1A2 can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Quizartinib: (Contraindicated) Avoid concomitant use of quizartinib and pimozide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Ranolazine: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of ranolazine with pimozide is contraindicated.
Rasagiline: (Major) Due to opposing effects on central dopaminergic activity, pimozide and rasagiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to pimozide. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Relugolix: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of relugolix with pimozide is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and TdP. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Relugolix; Estradiol; Norethindrone acetate: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of relugolix with pimozide is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and TdP. 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 pimozide, can potentiate the effects of remifentanil on respiration, sedation, and hypotension.
Remimazolam: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including benzodiazepines.
Ribociclib: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of ribociclib with pimozide is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and TdP. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Additionally, ribociclib is a strong CYP3A4 inhibitor. Pimozide is partially metabolized by CYP3A4, and has a narrow therapeutic window; coadministration may increase systemic exposure to pimozide.
Ribociclib; Letrozole: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of ribociclib with pimozide is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and TdP. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Additionally, ribociclib is a strong CYP3A4 inhibitor. Pimozide is partially metabolized by CYP3A4, and has a narrow therapeutic window; coadministration may increase systemic exposure to pimozide.
Rilpivirine: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP) and coadministration with other drugs associated with a possible risk for QT prolongation and TdP, such as rilpivirine, should be avoided.
Risperidone: (Contraindicated) Risperidone has a risk of QT prolongation and is contraindicated with pimozide. Concurrent use of pimozide with atypical agents may increase the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Ritlecitinib: (Major) Avoid concomitant use of pimozide and ritlecitinib. Concomitant use may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is CYP3A and CYP1A2 substrate, and ritlecitinib is a moderate CYP3A and CYP1A2 inhibitor.
Rolapitant: (Contraindicated) Because of the potential for QT prolongation and torsade de pointes (TdP), concurrent use of pimozide and rolapitant is contraindicated. Pimozide is a CYP2D6 substrate and rolapitant is a moderate CYP2D6 inhibitor; the inhibitory effect of rolapitant is expected to persist beyond 28 days for an unknown duration. Pimozide is associated with an established risk of QT prolongation and torsade de pointes (TdP); a significant increase in plasma concentrations may increase this risk.
Romidepsin: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of romidepsin with pimozide is contraindicated.
Ropinirole: (Major) Due to opposing effects o n central dopaminergic activity, pimozide and ropinirole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to pimozide. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Rotigotine: (Major) Due to opposing effects on central dopaminergic activity, pimozide and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to pimozide. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. In addition, coadministration may result in additive sedation.
Rucaparib: (Major) Avoid coadministration of pimozide with rucaparib due to the increased risk of cardiac effects. Pimozide is a CYP3A4 and CYP1A2 substrate. Rucaparib is a weak CYP3A4 inhibitor and a moderate CYP1A2 inhibitor. Ventricular arrhythmias associated with prolonged QT intervals have occurred with concomitant treatment with both strong and moderate CYP3A4 inhibitors; the manufacturer of pimozide advises that less potent CYP3A4 inhibitors should also be avoided. There is a theoretical potential for additional pimozide-related effects via inhibition of CYP1A2.
Safinamide: (Major) Due to opposing effects on central dopaminergic activity, pimozide and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to pimozide. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Sarilumab: (Moderate) Monitor for an altered patient response to pimozide if coadministration with sarilumab is necessary. Inhibition of IL-6 signaling by sarilumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as pimozide, may have fluctuations in drug levels and therapeutic effect when sarilumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping sarilumab. In vitro, sarilumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Pimozide a substrate of both CYP2D6 and CYP3A4 and narrow therapeutic index drug.
Secukinumab: (Moderate) If secukinumab is initiated or discontinued in a patient taking pimozide, monitor for altered patient response to pimozide; pimozide dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during secukinumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as pimozide.
Selective serotonin reuptake inhibitors: (Contraindicated) Pimozide is contraindicated for use with selective serotonin reuptake inhibitors (SSRIs) due to an increased risk of QT prolongation and torsade de pointes (TdP). Pimozide is thought to be primarily metabolized through CYP3A4, and to a lesser extent, CYP1A2 and CYP2D6. Elevated plasma concentrations of pimozide occurring through inhibition of one or more of these isoenzymes by SSRIs can lead to QT prolongation, ventricular arrhythmias, and sudden death. Additionally, most SSRIs are also associated with QT prolongation, further increasing the risk of additive QT prolongation.
Selegiline: (Major) Due to opposing effects on central dopaminergic activity, pimozide and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to pimozide. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Selpercatinib: (Contraindicated) Coadministration of pimozide with selpercatinib is contraindicated due to the risk for additive QT prolongation and torsade de pointes (TdP). Pimozide is associated with a well-established risk of QT prolongation and TdP. Selpercatinib can cause concentration-dependent interval prolongation.
Sertraline: (Contraindicated) Pimozide is contraindicated for use with selective serotonin reuptake inhibitors (SSRIs) due to an increased risk of QT prolongation and torsade de pointes (TdP). Pimozide is thought to be primarily metabolized through CYP3A4, and to a lesser extent, CYP1A2 and CYP2D6. Elevated plasma concentrations of pimozide occurring through inhibition of one or more of these isoenzymes by SSRIs can lead to QT prolongation, ventricular arrhythmias, and sudden death. Additionally, most SSRIs are also associated with QT prolongation, further increasing the risk of additive QT prolongation.
Sevoflurane: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of sevoflurane with pimozide is contraindicated.
Siltuximab: (Moderate) Monitor for an altered patient response to pimozide if coadministration with siltuximab is necessary. Inhibition of IL-6 signaling by siltuximab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as pimozide, may have fluctuations in drug levels and therapeutic effect when siltuximab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping siltuximab. In vitro, siltuximab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Pimozide a substrate of both CYP2D6 and CYP3A4 and narrow therapeutic index drug.
Siponimod: (Contraindicated) Concomitant use of siponimod and pimozide is contraindicated due to the potential for additive QT prolongation. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes.
Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as sodium phosphate, dibasic, sodium phosphate monobasic when used as an enema or bowel cleanser. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia.
Sodium Stibogluconate: (Contraindicated) Avoid concomitant use of sodium stibogluconate and pimozide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Solifenacin: (Contraindicated) Because of the potential for torsade de pointes (TdP), concurrent use of pimozide and solifenacin is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and TdP. Solifenacin has been associated dose-dependent prolongation of the QT interval. TdP has been reported with post-marketing use, although causality was not determined.
Sorafenib: (Contraindicated) Because of the potential for TdP, use of sorafenib with pimozide is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Sorafenib has also been associated with QT prolongation.
Sotalol: (Contraindicated) Avoid concomitant use of sotalol and pimozide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Spironolactone: (Major) Avoid concomitant use of pimozide and spironolactone. Concomitant use may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is CYP3A substrate, and spironolactone is a weak CYP3A inhibitor.
Spironolactone; Hydrochlorothiazide, HCTZ: (Major) Avoid concomitant use of pimozide and spironolactone. Concomitant use may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is CYP3A substrate, and spironolactone is a weak CYP3A inhibitor. (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and pimozide. CNS depressants can potentiate the effects of stiripentol. Consider a dose adjustment of pimozide when coadministered with stiripentol. Coadministration may alter plasma concentrations of pimozide resulting in an increased risk of adverse reactions and/or decreased efficacy. Pimozide is a CYP3A4 and CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP3A4 and CYP1A2 by stiripentol potentially resulting in clinically significant interactions.
Streptogramins: (Major) Avoid concurrent use of pimozide and dalfopristin; quinupristin. Elevated pimozide concentrations occurring through inhibition of CYP3A4 can lead to QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is metabolized primarily through CYP3A4, and dalfopristin; quinupristin is a weak CYP3A4 inhibitor.
Sufentanil: (Moderate) Concomitant use of sufentanil with other CNS depressants, such as pimozide, can potentiate sufentanil-induced CNS and cardiovascular effects and the duration of these effects.
Sunitinib: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of sunitinib with pimozide is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and TdP. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.
Tacrolimus: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of tacrolimus with pimozide is contraindicated.
Tamoxifen: (Contraindicated) Avoid concomitant use of tamoxifen and pimozide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
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: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of telavancin with pimozide is contraindicated.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Temazepam: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including benzodiazepines.
Terbinafine: (Contraindicated) Coadministration of pimozide and terbinafine is contraindicated due to the potential for increased pimozide exposure. Elevated concentrations of pimozide can lead to QT prolongation, ventricular arrhythmias, and sudden death. Terbinafine is a strong CYP2D6 inhibitor; pimozide is a CYP2D6 substrate. Coadministration of pimozide with another strong CYP2D6 inhibitor increased the pimozide AUC by 151%.
Tetrabenazine: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of tetrabenazine with pimozide is contraindicated.
Tezacaftor; Ivacaftor: (Minor) Use caution when administering ivacaftor and pimozide concurrently. Ivacaftor is an inhibitor of CYP3A and pimozide is partially metabolized by CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as pimozide, can theoretically increase pimozide exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
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 pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Thioridazine: (Contraindicated) Pimozide and thioridazine are both associated with a well-established risk of QT prolongation and torsade de pointes (TdP); therefore, concurrent use is contraindicated. Concurrent use of pimozide with phenothiazines may also increase the risk of serious adverse effects such as extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures.
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.
Tocilizumab: (Moderate) Monitor for an altered patient response to pimozide if coadministration with tocilizumab is necessary. Inhibition of IL-6 signaling by tocilizumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index, such as pimozide, may have fluctuations in drug levels and therapeutic effect when tocilizumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping tocilizumab. In vitro, tocilizumab has the potential to affect expression of multiple CYP enzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Pimozide is a substrate of both CYP2D6 and CYP3A4 and narrow therapeutic index drug.
Tolterodine: (Contraindicated) Because of the potential for torsade de pointes (TdP), concurrent use of tolterodine and pimozide is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and TdP and tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers.
Toremifene: (Contraindicated) Coadministration of toremifene with pimozide is contraindicated because of the potential for torsade de pointes (TdP). Pimozide is associated with a well-established risk of QT prolongation and TdP. 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 pimozide and loop diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Tramadol: (Major) Concurrent use of tramadol and pimozide should be avoided if possible. Antipsychotics may enhance the seizure risk of tramadol. Additive CNS depression may also be seen with the concomitant use of tramadol and pimozide.
Tramadol; Acetaminophen: (Major) Concurrent use of tramadol and pimozide should be avoided if possible. Antipsychotics may enhance the seizure risk of tramadol. Additive CNS depression may also be seen with the concomitant use of tramadol and pimozide.
Trandolapril; Verapamil: (Major) Concurrent use of pimozide and verapamil should be avoided. Pimozide is metabolized primarily through CYP3A4, and verapamil is a CYP3A4 inhibitor. Elevated pimozide concentrations occurring through inhibition of CYP3A4 can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Trazodone: (Contraindicated) Avoid concomitant use of trazodone and pimozide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Triamcinolone: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Triazolam: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including benzodiazepines.
Triclabendazole: (Contraindicated) Avoid concomitant use of triclabendazole and pimozide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Tricyclic antidepressants: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of tricyclic antidepressants with pimozide is contraindicated.
Trifluoperazine: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of pimozide with trifluoperazine is contraindicated. Concurrent use of pimozide with phenothiazines 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. Many phenothiazines are inhibitors of CYP2D6, one of the metabolic pathways of pimozide.
Triprolidine: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Triptorelin: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of triptorelin with pimozide is contraindicated; the efficacy of triptorelin may also be reduced. Pimozide is associated with a well-established risk of QT prolongation and TdP. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval. Pimozide can also cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
Trofinetide: (Major) Avoid concomitant use of pimozide and trofinetide. Concomitant use may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is CYP3A substrate, and trofinetide is a weak CYP3A inhibitor.
Tucatinib: (Contraindicated) Concurrent use of pimozide and tucatinib is contraindicated. Pimozide is metabolized primarily through CYP3A4, and tucatinib is a strong CYP3A4 inhibitor. Elevated pimozide concentrations occurring through inhibition of CYP3A4 can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of pimozide and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Vandetanib: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner. TdP and sudden death have been reported in patients receiving vandetanib. Because of the potential for TdP, use of vandetanib with pimozide is contraindicated.
Vardenafil: (Contraindicated) Avoid concomitant use of vardenafil and pimozide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Vemurafenib: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of vemurafenib with pimozide is contraindicated.
Venlafaxine: (Contraindicated) Avoid concomitant use of venlafaxine and pimozide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Verapamil: (Major) Concurrent use of pimozide and verapamil should be avoided. Pimozide is metabolized primarily through CYP3A4, and verapamil is a CYP3A4 inhibitor. Elevated pimozide concentrations occurring through inhibition of CYP3A4 can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Viloxazine: (Major) Avoid concomitant use of pimozide and viloxazine. Concomitant use may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is a CYP3A, 2D6 and 1A2 substrate, and viloxazine is a strong CYP1A2, weak CYP2D6, and weak CYP3A inhibitor.
Voclosporin: (Contraindicated) Concomitant use of voclosporin and pimozide is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). Pimozide is associated with a well-established risk of QT prolongation and TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Vonoprazan; Amoxicillin: (Major) Avoid concomitant use of pimozide and vonoprazan. Concomitant use may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is CYP3A substrate and vonoprazan is a weak CYP3A inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of macrolide antibiotics with pimozide is contraindicated. (Major) Avoid concomitant use of pimozide and vonoprazan. Concomitant use may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is CYP3A substrate and vonoprazan is a weak CYP3A inhibitor.
Voriconazole: (Contraindicated) Concurrent use of pimozide and voriconazole is contraindicated. Pimozide is metabolized primarily through CYP3A4, and voriconazole is a potent CYP3A4 inhibitor. Elevated pimozide concentrations occurring through inhibition of CYP3A4 can lead to QT prolongation, ventricular arrhythmias, and sudden death. The manufacturer of voriconazole contraindicates concurrent use with pimozide due to inhibition of CYP3A4 by voriconazole and the potential for pimozide toxicity. Furthermore, voriconazole is associated with QT prolongation; therefore, use with pimozide is contraindicated.
Vorinostat: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of vorinostat with pimozide is contraindicated.
Voxelotor: (Major) Avoid concomitant use of pimozide and voxelotor. Concomitant use may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is CYP3A substrate and voxelotor is a moderate CYP3A inhibitor.
Zafirlukast: (Contraindicated) Concurrent use of pimozide and zafirlukast should be avoided. Pimozide is metabolized primarily through CYP3A4, and to a lesser extent CYP1A2 and CYP2D6. Zafirlukast is a strong inhibitor of CYP1A2 and a lesser inhibitor of CYP3A4. Increased pimozide concentrations may occur, and can lead to QT prolongation, ventricular arrhythmias, and sudden death. Consider alternatives to zafirlukast.
Zaleplon: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedatives and hypnotics like zaleplon. In premarketing studies, zaleplon potentiated the CNS effects of ethanol, imipramine, and thioridazine for at least 2 to 4 hours and may result in similar interactions with other antipsychotics, including pimozide.
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 pimozide. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Zileuton: (Major) Avoid concomitant use of pimozide and zileuton as use may increase pimozide exposure and the risk for pimozide-related adverse reactions, including QT prolongation and ventricular arrhythmias.
Ziprasidone: (Contraindicated) Concomitant use of ziprasidone and pimozide is contraindicated by the manufacturer of ziprasidone due to the potential for additive QT prolongation and torsade de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of TdP in patients with multiple confounding factors. Pimozide is associated with a well-established risk of QT prolongation and TdP. In addition, coadministration of ziprasidone with pimozide 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) Additive CNS-depressant effects may occur when the antipsychotic pimozide is combined with zolpidem. In addition, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of zolpidem and other CNS depressants than with zolpidem alone.
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.

Orap/Pimozide Oral Tab: 1mg, 2mg

Adults

0.2 mg/kg/day PO or 10 mg/day PO, whichever is less.

Geriatric

0.2 mg/kg/day PO or 10 mg/day PO, whichever is less.

Adolescents

0.2 mg/kg/day PO or 10 mg/day PO, whichever is less.

Children

8 to 12 years: Do not exceed 0.2 mg/kg/day or 10 mg/day PO, whichever is less. Published data suggest a maximum of 6 mg/day PO or 0.2 mg/kg/day PO, whichever is less, for children less than 12 years old.
Less than 8 years: Safety and efficacy have not been established.

Infants

Not indicated.

Pimozide is a high-affinity central dopamine-2 (D2) receptor antagonist. Postsynaptic receptor sites are primarily affected. Blockade of D2 in the mesolimbic area of the brain reduces hallucinations and delusions and blockade in the nigrostriatal pathway is likely responsible for the extrapyramidal symptoms (EPS) which occur. In addition, D2 antagonism in the tuberoinfundibular tract of the brain is responsible for the hyperprolactinemia typically seen with antipsychotics. Blockade of dopamine receptors in the chemoreceptor trigger zone (CTZ) may account for the antiemetic action of pimozide. The weak alpha-blocking effects of the drug will rarely cause orthostatic hypotension and tachycardia. A variety of ECG changes can occur including QT interval prolongation; flattening, notching, and inversion of the T wave; and U wave appearance. Predictably, pimozide has less anticholinergic effects than low potency agents. Reduction in serotonin turnover in the hippocampus occurs, which may indirectly affect dopamine transmission. Unlike other antipsychotics, pimozide has little or no effect on norepinephrine. In addition, pimozide, in common with other antipsychotic drugs, has various effects on other central nervous system receptor systems which are not fully characterized.

Pimozide is administered orally. The drug is highly bound to plasma proteins (99%). Pimozide is extensively metabolized, primarily by N-dealkylation in the liver. This metabolism is catalyzed mainly by CYP3A4, CYP1A2, and CYP2D6. Two major metabolites have been identified, but the antipsychotic activity of these metabolites is undetermined. Poor metabolizers of CYP2D6 demonstrate higher pimozide concentrations and take longer to reach steady-state after dose changes than extensive CYP2D6 metabolizers. The mean elimination half-life of pimozide is 55 hours. The primary elimination route of pimozide and its metabolites is through the kidneys; less than 1% of a dose is renally eliminated as pimozide. A portion of the parent compound is excreted in the feces, but it is unclear if this is the result of unabsorbed drug or biliary elimination.
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A4, CYP2D6, CYP1A2
Major isoenzymes involved in the metabolism of pimozide include CYP3A4, CYP2D6, and CYP1A2. Interactions may potentially occur with other drugs that preferentially inhibit or induce these enzymes. Due to the potential for QT prolongation or torsade de pointes, concurrent use of pimozide and potent CYP2D6 or CYP3A4 inhibitors is contraindicated. Treatment guidelines recommend avoiding concurrent use of pimozide with CYP1A2 inhibitors or inducers. In vitro data suggest that pimozide has inhibitory effects on CYP2D6.

Oral Route

Following oral administration, 50% or more of the dose is absorbed from the gastrointestinal tract. It is not known if food affects absorption. Peak serum concentrations occur 6 to 8 hours after a dose (Range: 4 to 12 hours).

Pregnancy

Pimozide is best avoided during breast-feeding, where possible. According to the manufacturer, it is not known if pimozide is excreted into human breast milk and because of the potential for tumorigenicity and unknown cardiovascular effects in the infant, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pimozide may induce hyperprolactinemia and galactorrhea, and thus may interfere with proper lactation in some patients. 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, haloperidol is an alternate medication for consideration during breast-feeding for patients with Tourette's syndrome. In one small study, developmental delays were reported in some nursing babies following combined use of haloperidol and another antipsychotic, while monotherapy did not result in this outcome. Data regarding the safety of 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. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report adverse effects to the FDA.