ORAP
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ORAP (ORAP).
Orap (pimozide) is a diphenylbutylpiperidine antipsychotic that selectively blocks dopamine D2 receptors in the central nervous system, with weak antagonism at alpha1-adrenergic and H1-histamine receptors. Its anti-dyskinetic effect in Tourette syndrome may also involve blockade of calcium channels.
| Metabolism | Primarily metabolized via CYP3A4 and CYP1A2, with minor contribution from CYP2D6. Two major metabolites are pimozide N-oxide and 4-(4-piperidinyl)-4-fluorobutyrophenone, which are inactive. |
| Excretion | Primarily hepatic metabolism; approximately 40% excreted in urine as metabolites, 15% in feces as unchanged drug and metabolites. |
| Half-life | Terminal elimination half-life is 20–40 hours (mean 27 hours). Steady-state achieved in 4–7 days. |
| Protein binding | Approximately 99% bound to plasma proteins (albumin and alpha-1 acid glycoprotein). |
| Volume of Distribution | 8–10 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is 40–50% due to first-pass metabolism. |
| Onset of Action | Oral: 2–4 hours for antipsychotic effect; peak effect may take several days to weeks. |
| Duration of Action | 24 hours after a single dose; requires once-daily dosing for sustained effect. |
| Action Class | Typical Antipsychotics |
| Brand Substitutes | Monozide 2mg Tablet, Pimolite 2mg Tablet, Arkazid 2mg Tablet, Neurap 2mg Tablet, Medip 2mg Tablet, Monozide 4mg Tablet, Pimolite 4mg Tablet, Neurap 4mg Tablet, Pimo 4mg Tablet, Medip 4mg Tablet |
Initial: 2 mg orally twice daily; maintenance: 2-10 mg twice daily. Maximum 20 mg/day.
| Dosage form | TABLET |
| Renal impairment | No specific guidelines; use caution in severe impairment (CrCl <30 mL/min) due to potential accumulation; consider dose reduction. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: contraindicated. |
| Pediatric use | Not recommended for children <12 years; for adolescents 12-18 years: initial 1-2 mg/day, titrate to 0.05-0.2 mg/kg/day (max 10 mg/day). |
| Geriatric use | Initial: 1-2 mg/day in divided doses; increase slowly due to increased sensitivity; monitor for hypotension and extrapyramidal symptoms. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ORAP (ORAP).
| Breastfeeding | Pimozide (ORAP) is excreted in breast milk; M/P ratio not established. Use caution due to potential adverse effects in the infant (e.g., sedation, extrapyramidal symptoms). |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no teratogenic effects at clinically relevant doses. Second/third trimester: Risk of extrapyramidal symptoms and neonatal withdrawal with late exposure. Overall, avoid unless benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
WARNING: Increased risk of death in elderly patients with dementia-related psychosis. Pimozide is not approved for the treatment of patients with dementia-related psychosis.
| Serious Effects |
["Congenital long QT syndrome or history of QT prolongation","History of cardiac arrhythmias (e.g., torsade de pointes, ventricular tachycardia)","Concurrent use of drugs that prolong QT interval (e.g., Class IA/III antiarrhythmics, certain antipsychotics, macrolides)","Hypokalemia or hypomagnesemia (must be corrected prior to use)","Concurrent use of CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole, ritonavir) due to increased pimozide levels and risk of arrhythmias","Severe CNS depression, comatose states","Parkinson's disease (relative contraindication due to dopamine blockade)","Hypersensitivity to pimozide or any component of the formulation"]
| Precautions | ["QT interval prolongation and torsade de pointes: contraindicated with congenital long QT syndrome, history of cardiac arrhythmias, or concurrent use of QT-prolonging drugs","Neuroleptic malignant syndrome (NMS): discontinue immediately if signs/symptoms occur","Tardive dyskinesia: risk increases with duration of therapy","Seizure threshold reduction: use cautiously in patients with epilepsy","Hepatic impairment: dose reduction may be necessary","Hypokalemia and hypomagnesemia: correct before initiating treatment","Concomitant use of CYP3A4 inhibitors (e.g., macrolides, azole antifungals) requires dose adjustment"] |
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| Monitor maternal ECG for QTc prolongation; fetal growth ultrasound if prolonged use. Monitor neonate for extrapyramidal symptoms and sedation after delivery. |
| Fertility Effects | May elevate prolactin levels, potentially causing menstrual irregularities, galactorrhea, and reduced fertility in females. In males, may decrease libido or cause erectile dysfunction. |