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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP3A4 inhibitors are contraindicated due to risk of QT prolongation Can cause QT prolongation and extrapyramidal symptoms.
| Breastfeeding | Pimozide is excreted into human breast milk; M/P ratio unknown. Due to potential for serious adverse reactions in nursing infants (e.g., extrapyramidal symptoms, sedation), breastfeeding is not recommended during therapy. |
| 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. |
■ FDA Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis.
| Common Effects | Extrapyramidal symptoms |
| Serious Effects |
QTc >450 ms, concomitant QT-prolonging drugs, congenital long QT syndrome, hypokalemia, hypomagnesemia, concomitant CYP3A4 inhibitors (e.g., macrolides, azole antifungals, HIV protease inhibitors), known hypersensitivity.
| Precautions | QT prolongation, neuroleptic malignant syndrome, tardive dyskinesia, hyperglycemia, orthostatic hypotension, and withdrawal symptoms. |
Loading safety data…
| 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. |