- Use Alternative (1)voxelotor will increase the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.xylometazolineMonitor Closely (1)pimozide increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.yohimbineMonitor Closely (1)pimozide increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.zafirlukastSerious - Use Alternative (1)zafirlukast increases levels of pimozide by decreasing metabolism. Contraindicated. Risk of QT interval prolongation.Minor (1)zafirlukast will increase the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.ziconotideMonitor Closely (1)pimozide and ziconotide both increase sedation. Use Caution/Monitor.zileutonSerious - Use Alternative (1)zileuton increases levels of pimozide by decreasing metabolism. Contraindicated. May prolong QTc interval.ziprasidoneContraindicated (1)pimozide and ziprasidone both increase QTc interval. Contraindicated.Monitor Closely (2)pimozide and ziprasidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. pimozide and ziprasidone both increase sedation. Use Caution/Monitor.zolmitriptanMonitor Closely (1)zolmitriptan, pimozide. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).zotepineMonitor Closely (2)pimozide and zotepine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. pimozide and zotepine both increase sedation. Use Caution/Monitor. >10% Akinesia (40%) Drowsiness (35%) EPS (10-15%) Sedation (70%) Speech disorder (10-15%) Visual disturbance (20%) Dry mouth (25%) Constipation (20%) Impotence (10-15%) 1-10% Appetite increase Thirst increase Dizziness Drug-induced tardive dystonia Nervousness Photosensitivity Taste change Orthostatic hypotension Diminished sweating Nasal congestion Diarrhea Urinary retention Retinitis pigmentosa Frequency Not Defined Ineffective thermoregulation Heatstroke or hypothermia (rare) Neuroleptic malignant syndrome (rare) Seizure (rare) Prolonged QT interval Torsades de pointes Obstipation (rare) Paralytic ileus (rare) Agranulocytosis (rare) Disorder of hematopoietic structure (rare) Leukopenia (rare) Thrombocytopenia (rare) Cholestatic jaundice syndrome (rare) Drug-induced lupus erythematosus, systemic (rare) Priapism (rare) Death Contraindications Documented hypersensitivity Severe toxic central nervous system depression or comatose states from any cause Concomitant use with citalopram, escitalopram, sertraline Use as first-line treatment Tics not associated with Tourette's Drugs that may, themselves, cause motor and phonic tics (eg, pemoline, methylphenidate and amphetamines) 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 Concurrent QT-prolonging drugs; patients with congenital long QT syndrome, history of cardiac arrhythmias, taking other drugs which prolong the QT interval of the electrocardiogram or patients with known hypokalemia or hypomagnesemia Concomitant CYP3A4 or CYP2D6 inhibitors Cautions Avoid grapefruit juice Leukopenia/neutropenia and agranulocytosis reported; possible risk factors for leukopenia/neutropenia include pre-existing low white blood cell count (WBC) and history of drug-induced leukopenia/neutropenia If history of clinically significant low WBC or drug-induced leukopenia/neutropenia, monitor complete blood count (CBC) frequently during first few months of therapy; discontinue drug at first sign of a clinically significant decline <1000/mm³ in WBC in absence of other causative factors and continue monitoring WBC until recovery Patients with dementia-related psychosis who are treated with antipsychotic drugs are at an increased risk of death as shown in short-term controlled trials; The deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. This drug is not approved for the treatment of patients with dementia-related psychosis Sudden, unexpected deaths reported in experimental studies of conditions other than Tourette’s Disorder treated with antipsychotic drugs; these deaths occurred while patients were receiving dosages in the range of 1 mg per kg; the deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature; one possible mechanism for such deaths is prolongation of QT interval predisposing patients to ventricular arrhythmia; an electrocardiogram should be performed before treatment is initiated and periodically thereafter, especially during the period of dose adjustment This drug may have a tumorigenic potential; based on studies conducted in mice, it is known that pimozide can produce a dose-related increase in pituitary tumors; the full significance of this finding is not known, but should be taken into consideration in the physician's and patient’s decisions to use this drug product; this finding should be given special consideration when the patient is young and chronic use of pimozide is anticipated This medication may impair mental and/or physical abilities required for performance of potentially hazardous tasks, such as driving a car or operating machinery, especially during first few days of therapy Produces anticholinergic side effects and should be used with caution in individuals whose conditions may be aggravated by anticholinergic activity Therapy should be administered cautiously to patients with impairment of liver or kidney function because it is metabolized by the liver and excreted by the kidneys Antipsychotics should be administered with caution to patients receiving anticonvulsant medication, with a history of seizures, or with EEG abnormalities, because they may lower the convulsive threshold; if indicated, adequate anticonvulsant therapy should be maintained concomitantly Tardive dyskinesia A syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs; although prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown; both the risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as duration of treatment and total cumulativedose of antipsychotic drugs administered to patient increase However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses; there is no known treatment for established cases of tardive dyskinesia, although thesyndrome may remit, partially or completely, if antipsychotic treatment is withdrawn Antipsychotic treatment itself, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask underlying process The effect that symptomatic suppression has upon long-term course of the syndrome is unknown; given these considerations, antipsychotic drugs should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that, is known to respond to antipsychotic drugs, and, for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate In patients who do require chronic treatment, the smallest dose and shortest duration of treatment producing a satisfactory clinical response should be sought; the need for continued treatment should be reassessed periodically If signs and symptoms of tardive dyskinesia appear in a patient on antipsychotics, drug discontinuation should be considered; however, some patients may require treatment despite the presence of the syndrome Neuroleptic malignant syndrome A potentially fatal symptom complex sometimes referred to as neuroleptic malignant syndrome (NMS) reported in association with antipsychotic drugs; clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status (including catatonic signs), and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias); additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where clinical presentation includes both serious medical illness (eg, pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS); other important considerations in differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system (CNS) pathology The management of NMS should include immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, intensive symptomatic treatment and medical monitoring, and treatment of any concomitant serious medical problems for which specific treatments are available; there is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered; the patient should be carefully monitored since recurrences of NMS have been reported; hyperpyrexia, not associated with the above symptom complex, has been reported with other antipsychotic drugs Pregnancy Category: C Neonates exposed to antipsychotic drugs during the 3rd trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery These complications vary in severity; in some cases, symptoms have been self-limited, while in other cases neonates have required intensive care unit support and prolonged hospitalization Lactation: unknown, avoidPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Phenylbutylpiperadine; potent centrally acting dopamine D2 receptor antagonist Absorption Bioavailability: 40-50% Peak plasma time: 6-8 hr Peak plasma concentration: 4-19 ng/mL (dose dependent) Metabolism Metabolism: Hepatic P450 enzyme CYP3A4 and CYP2D6 Metabolites: Inactive Elimination Half-life elimination: 55 hr Excretion: Urine Dialyzable: Unknown Pharmacogenetics Poor CYP2D6 metabolizers exhibit higher pimozide concentrations than extensive CYP2D6 metabolizers Approximately 7-10% of Caucasians and 3-8% of African Americans lack the capacity to metabolize CYP2D6 substrates and are classified as poor metabolizers (PMs) Serum concentrations observed in poor metabolizers are similar to those seen with strong CYP2D6 inhibitors (eg, paroxetine) Time to achieve steady state pimozide concentrations is expected to be longer (approximately 2 weeks) in poor metabolizers because of the prolonged half-life Alternative dosing strategies are recommended in patients who are genetically poor CYP2D6 metabolizers Genetic testing laboratories Genotyping tests for CYP2D6 variants are commercially available through the following companies Applied Biosystems (http://www.appliedbiosystems.com/) GenPath Diagnostics (http://www.genpathdiagnostics.com/) BRAND FORM. UNIT PRICE PILL IMAGE pimozide oral- 1 mg tabletpimozide oral- 2 mg tabletCopyright © 2010 First DataBank, Inc.Print Patient Educationpimozide oral PIMOZIDE - ORAL (PIM-oh-zide) COMMON BRAND NAME(S): Orap USES: This medication is used to reduce uncontrolled movements (motor tics) or outbursts of words/sounds (vocal tics) caused by Tourette syndrome. Pimozide is a medication that works by decreasing the activity of a natural substance (dopamine) in the brain.Pimozide should not be used for mild symptoms. It should only be used if symptoms cause severe problems in everyday life and other medicines or treatments have not been effective. HOW TO USE: Take this medication by mouth with or without food as directed by your doctor, usually once a day at bedtime.The dosage is based on your medical condition, lab tests, and response to treatment. Your doctor may direct you to take a low dose at first, gradually increasing the dose to lower the chance of side effects such as shaking (tremors).Do not take this drug more often or increase the dose. Your symptoms will not improve any faster, and the risk for heart rhythm problems will be increased. Follow your doctor's directions carefully.Your doctor may order an electrocardiogram (EKG) and laboratory tests before you start this medication. These tests are to find out whether you are at risk for heart rhythm problems from pimozide. Keep all medical/lab appointments.Other drugs, such as stimulant medications (such as methylphenidate, dextroamphetamine), may occasionally worsen tics. Before deciding to start pimozide, your doctor may try to reduce your tics by lowering the stimulant dose. Consult your doctor for more details.Avoid eating grapefruit or drinking grapefruit juice while using this medication unless your doctor or pharmacist says you may do so safely. Grapefruit can increase the chance of side effects with this medicine. Ask your doctor or pharmacist for more details.Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day.Do not stop taking this medication without consulting your doctor. Your condition may become worse when