PROLIXIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROLIXIN (PROLIXIN).
Fluphenazine is a typical antipsychotic that blocks postsynaptic dopamine D2 receptors in the central nervous system. It also exhibits alpha-adrenergic blocking activity and anticholinergic effects.
| Metabolism | Fluphenazine is extensively metabolized in the liver via sulfoxidation, N-hydroxylation, and glucuronidation. CYP2D6 is involved in its metabolism. |
| Excretion | Primarily renal (70-80% as metabolites, <1% unchanged) and biliary/fecal (20-30%) |
| Half-life | Terminal half-life 14-24 hours; clinical context: allows once-daily or twice-daily dosing |
| Protein binding | 90-95% bound to albumin and alpha1-acid glycoprotein |
| Volume of Distribution | 10-20 L/kg; extensive tissue distribution |
| Bioavailability | Oral: ~50% due to first-pass metabolism; IM: 100% |
| Onset of Action | Oral: 30-60 minutes; Intramuscular: 10-20 minutes |
| Duration of Action | Oral: 6-12 hours; IM: 4-6 hours; clinical notes: decanoate form (not listed) has longer duration |
Initial: 2.5-10 mg orally every 6-8 hours; maintenance: 1-5 mg orally every 6-8 hours. Maximum 40 mg/day. For deep IM: 2.5-10 mg every 6-8 hours.
| Dosage form | ELIXIR |
| Renal impairment | No specific dosage adjustment guidelines; use with caution in renal impairment. For GFR <10 mL/min: administer 50-70% of normal dose. |
| Liver impairment | Contraindicated in severe hepatic dysfunction (Child-Pugh Class C). In mild to moderate impairment (Child-Pugh A/B): reduce dose by 50-75% and monitor closely. |
| Pediatric use | Children >12 years: 0.25-0.5 mg/kg/day orally in divided doses every 6-8 hours, not to exceed 10 mg/day. IM: 0.025-0.05 mg/kg/dose every 6-8 hours. |
| Geriatric use | Initial: 1-2.5 mg orally every 8-12 hours; increase gradually. Use lower doses due to increased sensitivity and risk of extrapyramidal symptoms, sedation, and orthostatic hypotension. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROLIXIN (PROLIXIN).
| Breastfeeding | Breastfeeding safety is not well established. Fluphenazine (PROLIXIN) is excreted in breast milk; M/P ratio unknown. Potential for adverse effects in infant (drowsiness, extrapyramidal symptoms). Weigh benefits of breastfeeding against potential risks; consider lowest effective dose of alternative antipsychotic if necessary. |
| Teratogenic Risk | First trimester: Limited data; possible increased risk of malformations (neural tube defects, cardiovascular anomalies) with high doses; avoid if possible. Second and third trimesters: Risk of extrapyramidal symptoms and withdrawal in neonate, especially with chronic use; also risk of transient neonatal hypertonicity. Consider risk-benefit. |
■ FDA Black Box Warning
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at increased risk of death. Fluphenazine is not approved for the treatment of dementia-related psychosis.
| Serious Effects |
["Comatose states","CNS depression","Subcortical brain damage","Blood dyscrasias","Liver damage","Known hypersensitivity to fluphenazine or other phenothiazines","Concurrent use of high doses of CNS depressants"]
| Precautions | ["Tardive dyskinesia","Neuroleptic malignant syndrome","QT prolongation","Seizures","Leukopenia/neutropenia/agranulocytosis","Hypotension","Cholestatic jaundice"] |
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| Fetal Monitoring | Monitor maternal for extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome (NMS). Monitor fetal growth with ultrasound if chronic use. Monitor neonate for extrapyramidal symptoms, withdrawal, hypertonicity, and respiratory depression after birth. |
| Fertility Effects | Fluphenazine may cause hyperprolactinemia, leading to menstrual irregularities, anovulation, and reduced fertility. Also may cause galactorrhea and sexual dysfunction. Effects are reversible upon discontinuation. |