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pimozide (Orap)

Tradename: Orap. Indications: - suppression of severe motor tics & phonic tics in patients with Tourette's syndrome Contraindications: 1) simple tics, not due to Tourette's syndrome 2) history of cardiac dysrhythmias 3) CNS depression 4) blood dyscrasias 5) depressive disorders 6) parkinsonism Caution: 1) treatment imposes serious risks to patient 2) benefits must outweigh risks Dosage: 1) start 1-2 mg PO QD 2) most patients respond to 10 mg/day 3) maximum: 20 mg/day Tabs: 2 mg. Reduction of dose for hepatic insufficiency Pharmacokinetics: 1) oral absorption is 40-50% 2) protein-binding is 99% 3) metabolized in the liver by cyt P450 3A4 -> significant 1st pass metabolism in liver 4) elimination 1/2life of 55 hours 5) time to peak serum concentration: within 6-8 hours 6) metabolites excreted in the urine Adverse effects: 1) common (> 10%) - akathisia, akinesia, extrapyramidal effects, tachycardia, orthostatic hypotension, constipation, drowsiness dry mouth, rash, breast swelling 2) less common (1-10%) - tardive dyskinesia, diarrhea, anorexia, depression, swelling of the face 3) uncommon (< 1%) - jaundice, blood dyscrasias, neuroleptic malignant syndrome 4) other - tumorogenic in animal studies - altered mental status - autonomic instability - lowers seizure threshold Drug interactions: 1) increased effect & toxicity of: - alfentanil, CNS depressants, guanabenz, MAO inhibitors, agents which prolong the QT interval 2) may exacerbate adverse effects of anticholinergic agents 3) any drug that inhibits cyt P450 3A4 may increase levels of pimozide 4) any drug that induces cyt P450 3A4 may diminish levels of pimozide

Interactions

drug interactions drug adverse effects (more general classes)

Related

cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4) Gilles de la Tourette's syndrome

General

antipsychotic agent benzimidazole

Properties

MISC-INFO: elimination route LIVER pregnancy-category C safety in lactation - protein-binding 99%

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  3. Department of Veterans Affairs, VA National Formulary