No

Antipsychotic Agent, Diphenylbutylperidine

Suppression of severe motor and phonic tics in patients with Tourette's disorder who have failed to respond satisfactorily to standard treatment

C

Hypersensitivity to pimozide or any component; severe CNS depression, coma, history of dysrhythmia, prolonged Q-T syndrome, concurrent use of macrolide antibiotics (such as erythromycin or clarithromycin), azole antifungals, simple tics other than Tourette's, protease inhibitors (ie, ritonavir, saquinavir, indinavir, nelfinavir), nefazodone, and zileuton; concomitant use of drugs that inhibit CYP3A3/4.

May cause hypotension, use with caution in patients with autonomic instability. Moderately sedating, use with caution in disorders where CNS depression is a feature. Use with caution in Parkinson's disease. Caution in patients with hemodynamic instability; bone marrow suppression; predisposition to seizures; subcortical brain damage; severe cardiac, hepatic, renal, or respiratory disease. Esophageal dysmotility and aspiration have been associated with antipsychotic use - use with caution in patients at risk of pneumonia (ie, Alzheimer's disease). Caution in breast cancer or other prolactin-dependent tumors (may elevate prolactin levels). May alter temperature regulation or mask toxicity of other drugs due to antiemetic effects. May alter cardiac conduction - life-threatening arrhythmias have occurred with high doses (> 10 mg). May prolong QT interval predisposing patients to ventricular arrhythmias. May cause orthostatic hypotension - use with caution in patients at risk of this effect or those who would tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, or other medications which may predispose).

May cause extrapyramidal reactions, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is high relative to other neuroleptics). May be associated with neuroleptic malignant syndrome (NMS) or pigmentary retinopathy.

Avoid grapefruit juice due to potential inhibition of pimozide metabolism

Cardiovascular: Swelling of face, tachycardia, orthostatic hypotension, chest pain, hypertension, palpitations, ventricular arrhythmias, QT prolongation

Central nervous system: Extrapyramidal signs (akathisia, akinesia, dystonia, pseudoparkinsonism, tardive dyskinesia), drowsiness, NMS, headache, dizziness, excitement

Dermatologic: Rash

Endocrine & metabolic: Edema of breasts, decreased libido

Gastrointestinal: Constipation, xerostomia, weight gain or loss, nausea, salivation, vomiting, anorexia

Genitourinary: Impotence

Hematologic: Blood dyscrasias

Hepatic: Jaundice

Neuromuscular & skeletal: Weakness, tremor

Ocular: Visual disturbance, decreased accommodation, blurred vision

Miscellaneous: Diaphoresis

Symptoms of overdose include hypotension, respiratory depression, EKG abnormalities, extrapyramidal symptoms

Following attempts at decontamination, treatment is supportive and symptomatic; seizures can be treated with diazepam, phenytoin, or phenobarbital

CYP3A3/4, CYP1A2 (minor) enzyme substrate

Benztropine (and other anticholinergics) may inhibit the therapeutic response to pimozide and excess anticholinergic effects may occur

Chloroquine may increase pimozide concentrations

Cigarette smoking may enhance the hepatic metabolism of pimozide. Larger doses may be required compared to a nonsmoker.

Concurrent use of pimozide with an antihypertensive may produce additive hypotensive effects

Antihypertensive effects of guanethidine and guanadrel may be inhibited by pimozide

Concurrent use with TCA may produce increased toxicity or altered therapeutic response

Pimozide may inhibit the antiparkinsonian effect of levodopa; avoid this combination

Pimozide plus lithium may rarely produce neurotoxicity

Barbiturates may reduce pimozide concentrations

Propranolol may increase pimozide concentrations

Sulfadoxine-pyrimethamine may increase pimozide concentrations

Pimozide and possibly other low potency antipsychotics may reverse the pressor effects of epinephrine

Pimozide and CNS depressants (ethanol, narcotics) may produce additive CNS depressant effects

Pimozide and trazodone may produce additive hypotensive effects

Carbamazepine may stimulate the metabolism of pimozide; monitor for reduced efficacy

Macrolide antibiotics (clarithromycin, erythromycin, dirithromycin, azithromycin and troleandomycin), azole antifungals, protease inhibitors, nefazodone, zileuton inhibit metabolism of pimozide and may predispose to life-threatening arrhythmias. Any inhibitor of CYP 3A3/4 is contraindicated.

Concurrent use with fluoxetine caused bradycardia (case report).

Protease inhibitors may increase pimozide's serum concentration. Concurrent use with ritonavir is contraindicated.

A potent centrally-acting dopamine-receptor antagonist resulting in its characteristic neuroleptic effects

Absorption: Oral: 50%

Protein binding: 99%

Metabolism: In the liver with significant first-pass decay

Half-life: 50 hours

Time to peak serum concentration: Within 6-8 hours

Elimination: In urine

Children >12 years and Adults: Oral: Initial: 1-2 mg/day, then increase dosage as needed every other day; range is usually 7-16 mg/day, maximum dose: 20 mg/day or 0.3 mg/kg/day should not be exceeded. Note: Sudden unexpected deaths have occurred in patients taking doses >10 mg.

prolactin (S)

No information available to require special precautions

>10% of patients experience dry mouth

Use exactly as directed (do not increase dose or frequency); may cause physical and/or psychological dependence. It may take 2-3 weeks to achieve desired results; do not discontinue without consulting prescriber. Avoid excess alcohol or caffeine and other prescription or OTC medications not approved by prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience excess drowsiness, restlessness, dizziness, or blurred vision (use caution driving or when engaging in tasks requiring alertness until response to drug is known); or constipation, dry mouth, anorexia (increased exercise, fluids, or dietary fruit and fiber may help). Report persistent CNS effects (eg, trembling fingers, altered gait or balance, excessive sedation, seizures, unusual muscle or facial movements, anxiety, abnormal thoughts, confusion, personality changes); unresolved constipation or gastrointestinal effects; breast swelling (male and female) or decreased sexual ability; vision changes; difficulty breathing; unusual cough or flu-like symptoms; or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding. Avoid grapefruit juice.

Perform EKG at baseline and periodically thereafter, and with dose increases; use in patients receiving macrolide antibiotics such as clarithromycin, erythromycin, azithromycin, and dirithromycin may predispose those patients to fatal cardiac arrhythmias

Tablet: 2 mg

Bruun RD, "Subtle and Under-Recognized Side Effects of Neuroleptic Treatment in Children With Tourette's Disorder," Am J Psychiatry, 1988, 145(5):621-4.

Krähenbühl S, Sauter B, Kupferschmidt H, et al, "Case Report: Reversible QT Prolongation With Torsade de Pointes in a Patient With Pimozide Intoxication," Am J Med Sci, 1995, 309(6):315-6.

Larkin C, "Epileptogenic Potential of Pimozide," Am J Psychiatry, 1983, 140(3):372-3.

Peabody CA, Warner MD, Whiteford HA, et al, "Neuroleptics and the Elderly," J Am Geriatr Soc, 1987, 35(3):233-8.

"Pimozide (Orap) Contraindicated With Clarithromycin (Biaxin™) and Other Macrolide Antibiotics," FDA Medical Bulletin, October 1996, 3.

Risse SC and Barnes R, "Pharmacologic Treatment of Agitation Associated With Dementia," J Am Geriatr Soc, 1986, 34(5):368-76.

Saltz BL, Woerner MG, Kane JM, et al, "Prospective Study of Tardive Dyskinesia Incidence in the Elderly," JAMA, 1991, 266(17):2402-6.

Seifert RD, "Therapeutic Drug Monitoring: Psychotropic Drugs," J Pharm Pract, 1984, 6:403-16.