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. |
| Molecular Weight | 461.55 |
| 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 | Limited human data; animal studies show risk. Use only if benefit outweighs risk. Avoid if possible. |
| 2nd trimester | Limited data; may cause extrapyramidal symptoms in newborn. Monitor for neonatal withdrawal. |
| 3rd trimester | Risk of neonatal extrapyramidal symptoms, agitation, feeding difficulties. Use with caution. |
Clinical note
Comprehensive clinical and safety monograph for ORAP (ORAP).
| Placental transfer | Crosses placenta; evidence from case reports and animal studies. Extent of transfer not fully quantified. |
| Breastfeeding | Pimozide is excreted into breast milk in small amounts. Monitor infant for drowsiness, irritability, and extrapyramidal symptoms. Consider risks versus benefits. |
| Lactation Rating |
■ 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 |
Hypersensitivity to pimozideLong QT syndrome or QTc >440 msConcomitant use of drugs that prolong QT intervalSevere CNS depressionComatose states
| 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 |
| Food/Dietary | Grapefruit juice increases pimozide levels and risk of QT prolongation; avoid concurrent use. Alcohol may enhance CNS depression. |
Loading safety data…
| L3 - Moderately Safe |
| 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 | 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. |
| Clinical Pearls | ORAP (pimozide) is a diphenylbutylpiperidine antipsychotic primarily used for Tourette's disorder. It prolongs the QT interval; obtain baseline ECG and monitor electrolytes. Avoid concurrent use with CYP3A4 and CYP2D6 inhibitors. Titrate slowly; maximum dose 10 mg/day. Watch for extrapyramidal symptoms and neuroleptic malignant syndrome. |
| Patient Advice | Take exactly as prescribed; do not stop abruptly. · Report fainting, fast heartbeat, or seizures immediately. · Avoid grapefruit juice during treatment. · May cause drowsiness; avoid driving until you know how it affects you. · Report involuntary movements or muscle stiffness. |