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 |
| Molecular Weight | 437.54 |
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 | Avoid use during first trimester unless benefits outweigh risks; associated with congenital malformations in animal studies, limited human data. |
| 2nd trimester | Use only if clearly needed; may cause neonatal adverse effects if used near term. |
| 3rd trimester | Avoid during third trimester due to risk of extrapyramidal symptoms and withdrawal in neonates. |
Clinical note
Comprehensive clinical and safety monograph for PROLIXIN (PROLIXIN).
| Placental transfer | Crosses placenta; measurable levels in fetal plasma and amniotic fluid. |
| Breastfeeding | Fluphenazine is excreted into breast milk in low amounts. Monitor infant for sedation, extrapyramidal symptoms, and poor feeding. Benefits of breastfeeding may outweigh risks in some cases. |
■ 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 patientsCNS depression due to alcohol or other depressantsBlood dyscrasiasKnown hypersensitivity to phenothiazinesSevere hepatic disease
| Precautions | Tardive dyskinesia, Neuroleptic malignant syndrome, QT prolongation, Seizures, Leukopenia/neutropenia/agranulocytosis, Hypotension, Cholestatic jaundice |
| Food/Dietary | Avoid alcohol and CNS depressants. No specific food interactions; maintain adequate hydration to reduce anticholinergic side effects. |
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| Lactation Rating |
| L3 (Moderately Safe) |
| 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. |
| 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. |
| Clinical Pearls |
| Prolixin (fluphenazine) is a high-potency first-generation antipsychotic. Monitor for extrapyramidal symptoms (EPS) especially akathisia and dystonia. Use lowest effective dose. Obtain baseline and periodic ECG due to QTc prolongation risk. Avoid in elderly with dementia due to increased mortality. Depot formulations (decanoate) require careful dose conversion from oral. |
| Patient Advice | Take exactly as prescribed; do not stop abruptly. · May cause drowsiness; avoid driving if affected. · Report muscle stiffness, tremors, restlessness, or involuntary movements. · Avoid alcohol and CNS depressants. · Use sun protection as photosensitivity may occur. · Contact doctor if fever, confusion, or irregular heartbeat occurs. |