PIMOZIDE
Clinical safety rating: safe
Animal studies have demonstrated safety
Blocks dopamine D2, D3, and D4 receptors; also 5-HT2A, α1-adrenergic, and H1 receptors.
| Metabolism | CYP3A4 and CYP1A2; minor via CYP2D6. |
| Excretion | Primarily hepatic metabolism; renal excretion of metabolites accounts for approximately 70-90% of eliminated drug; fecal excretion ~10-30%. |
| Half-life | Terminal elimination half-life is approximately 50-60 hours in adults; may be prolonged in elderly or hepatic impairment. |
| Protein binding | Approximately 99% bound to plasma proteins, including albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd approximately 20-40 L/kg, indicating extensive tissue distribution; high affinity for brain tissue. |
| Bioavailability | Oral bioavailability is 40-50% due to extensive first-pass hepatic metabolism. |
| Onset of Action | Oral: 1-2 hours for initial effect; peak clinical effect may take several days to weeks. |
| Duration of Action | Duration of action after a single oral dose is approximately 24 hours due to long half-life; steady-state achieved in 7-14 days. |
| Molecular Weight | 461.51 |
1-10 mg orally once daily; maximum 10 mg/day.
| Dosage form | TABLET |
| Renal impairment | No specific adjustment required; use caution in severe impairment. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use. |
| Pediatric use | 0.05-0.1 mg/kg orally once daily; maximum 10 mg/day. |
| Geriatric use | Initiate at lower dose (0.5-1 mg/day); titrate slowly due to increased sensitivity and risk of QT prolongation. |
| 1st trimester | Risk of teratogenicity; limited human data; use only if benefit outweighs risk. |
| 2nd trimester | Limited human data; avoid if possible. |
| 3rd trimester | Risk of neonatal extrapyramidal symptoms and withdrawal; avoid near term. |
Clinical note
Strong CYP3A4 inhibitors are contraindicated due to risk of QT prolongation Can cause QT prolongation and extrapyramidal symptoms.
| Placental transfer | Pimozide crosses the placenta; extent not well quantified but expected due to molecular weight and lipophilicity. |
| Breastfeeding | Pimozide is excreted into breast milk in low levels; monitor infant for sedation and extrapyramidal effects. Consider alternative agents. |
| Lactation Rating |
■ FDA Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis.
| Common Effects | Extrapyramidal symptoms |
| Serious Effects |
Known hypersensitivity to pimozideCongenital long QT syndromeHistory of QT prolongation or torsade de pointesConcomitant use of QT-prolonging drugs (e.g., macrolides, antifungals, antidepressants)Hypokalemia or hypomagnesemiaSevere hepatic impairmentParkinson's disease (relative, but often considered absolute due to risk of exacerbation)Concomitant use of CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin)
| Precautions | QT prolongation, neuroleptic malignant syndrome, tardive dyskinesia, hyperglycemia, orthostatic hypotension, and withdrawal symptoms. |
| Food/Dietary | Avoid grapefruit and grapefruit juice; increases pimozide levels and risk of QT prolongation. Avoid alcohol. Consume with food to reduce GI irritation. |
Loading safety data…
| L4 - Possibly Hazardous |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Limited human data; animal studies show fetal toxicity at high doses. Second and third trimesters: Risk of extrapyramidal symptoms and withdrawal in neonates if used near term. Not associated with major malformations in controlled studies. |
| Fetal Monitoring | Monitor maternal ECG for QTc prolongation, electrolytes, and liver function. Fetal monitoring: Growth ultrasound in third trimester if used long-term; neonatal assessment for extrapyramidal symptoms and sedation at delivery. |
| Fertility Effects | Pimozide may elevate prolactin levels, potentially causing menstrual irregularities, galactorrhea, and reversible infertility in females. Males may experience erectile dysfunction or decreased libido. |
| Clinical Pearls | Monitor QTc interval before and during therapy; discontinue if QTc > 500 ms. Titrate slowly to minimize EPS risk. Use with caution in patients with Parkinson's disease or dementia with Lewy bodies. Strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) and CYP2D6 inhibitors (e.g., paroxetine) increase pimozide levels and risk of arrhythmias; avoid coadministration. |
| Patient Advice | Do not consume grapefruit juice while taking pimozide. · Report fainting, palpitations, or seizures immediately. · May cause dizziness or drowsiness; avoid driving until you know how pimozide affects you. · Do not stop abruptly; taper under medical supervision. · Store at room temperature away from moisture and heat. |