PERMITIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PERMITIL (PERMITIL).
Antagonist at dopamine D2 receptors, also blocks alpha-1 adrenergic, histaminergic, and muscarinic receptors.
| Metabolism | Primarily hepatic via CYP2D6; minor contributions from CYP1A2, CYP3A4. |
| Excretion | Renal: <1% unchanged; Hepatic: extensively metabolized, metabolites excreted in urine (50-60%) and feces (30-40%) |
| Half-life | Terminal elimination half-life: 20-30 hours; clinically, steady-state achieved in 5-7 days; prolonged in elderly and hepatic impairment |
| Protein binding | 90-95% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 12-18 L/kg; high Vd indicates extensive tissue distribution (e.g., brain, lungs) |
| Bioavailability | Oral: 40-60% (extensive first-pass metabolism); IM: 70-80% |
| Onset of Action | Oral: 30-60 minutes; IM: 15-30 minutes; IV: 5-10 minutes |
| Duration of Action | Oral: 4-6 hours; IM: 4-6 hours; IV: 3-4 hours; clinical effects (e.g., antipsychotic) persist with repeated dosing |
2.5-10 mg orally every 8-12 hours; maximum 40 mg/day. For severe psychosis: initial 10 mg IM, then 5-10 mg IM every 6-8 hours; maximum 30 mg/day IM.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment recommended; use with caution in severe renal impairment (eGFR <10 mL/min). |
| Liver impairment | Child-Pugh A: reduce dose by 25-50%; Child-Pugh B: reduce dose by 50-75%; Child-Pugh C: avoid or use lowest possible dose with close monitoring. |
| Pediatric use | Children 6-12 years: 0.25-3.5 mg/day orally in divided doses; not recommended for children <6 years. IM: 0.01-0.03 mg/kg every 6-8 hours (max 1 mg/dose). |
| Geriatric use | Initial dose 0.5-1 mg orally once daily; titrate slowly by 0.5-1 mg increments; usual maintenance 1-5 mg daily; lower doses due to increased sensitivity and risk of adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PERMITIL (PERMITIL).
| Breastfeeding | Permetil (fluphenazine) is excreted into breast milk. M/P ratio not established. Effects on infant unknown, but potential for sedation, galactorrhea, and extrapyramidal reactions. Use only if essential; monitor infant for drowsiness and poor feeding. |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no consistent teratogenicity. Use only if benefit outweighs risk. Second/third trimester: Risk of extrapyramidal symptoms and withdrawal in neonates (e.g., abnormal muscle movements, agitation, poor feeding). Avoid in high doses near term due to potential for neonatal jaundice. |
■ FDA Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis.
| Serious Effects |
["Comatose states","CNS depression","Known hypersensitivity to fluphenazine","Blood dyscrasias","Hepatic impairment"]
| Precautions | ["Tardive dyskinesia","Neuroleptic malignant syndrome","QT prolongation","Hyperglycemia","Orthostatic hypotension"] |
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| Fetal Monitoring | Maternal: Baseline and periodic liver function tests, CBC, and ECG (if high doses or prolonged use). Monitor for extrapyramidal symptoms, tardive dyskinesia, and neuroleptic malignant syndrome. Fetal/neonatal: Ultrasound for fetal growth; neonatal observation for extrapyramidal symptoms, jaundice, and feeding difficulties. |
| Fertility Effects | May cause hyperprolactinemia, leading to menstrual irregularities, anovulation, and galactorrhea, potentially reducing fertility. Impact is reversible upon dose reduction or discontinuation. |