PROLIXIN DECANOATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROLIXIN DECANOATE (PROLIXIN DECANOATE).
Fluphenazine decanoate is a long-acting phenothiazine antipsychotic that blocks dopamine D1 and D2 receptors in the brain, particularly in the mesolimbic and mesocortical pathways, with higher affinity for D2 receptors. It also exhibits alpha-adrenergic blocking and anticholinergic activity.
| Metabolism | Extensively metabolized in the liver via sulfoxidation, N-hydroxylation, and glucuronidation; CYP2D6 is involved in metabolism; undergoes significant first-pass metabolism; has a long elimination half-life due to slow release from depot formulation. |
| Excretion | Renal (approximately 50% as conjugated metabolites, <1% unchanged) and fecal (approximately 30%, primarily via bile). |
| Half-life | Terminal elimination half-life approximately 14 days (range 6-25 days) after intramuscular injection, reflecting slow release from the oily depot; allows for every 2-4 week dosing. |
| Protein binding | Approximately 99% bound, primarily to albumin and alpha1-acid glycoprotein. |
| Volume of Distribution | Vd approximately 10 L/kg; indicates extensive tissue distribution, particularly into brain and adipose tissue. |
| Bioavailability | IM: 100% (administered as depot injection); oral: not applicable (only available as decanoate ester for intramuscular use). |
| Onset of Action | IM: 24-72 hours; onset is gradual due to slow release from ester. |
| Duration of Action | IM: 2-4 weeks; therapeutic effect maintained with single injection due to slow hydrolysis and extended half-life. |
Fluphenazine decanoate initial dose 12.5-25 mg IM or SC every 1-4 weeks; maintenance dose 12.5-50 mg every 2-4 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | No specific GFR-based adjustment required; use with caution in severe renal impairment (CrCl < 10 mL/min) due to increased risk of accumulation. |
| Liver impairment | Contraindicated in Child-Pugh class C; in Child-Pugh A or B, reduce dose by 50% and monitor hepatic function. |
| Pediatric use | Not recommended for children < 12 years; for adolescents (12-18 years), initial IM/SC dose 6.25-12.5 mg every 2-4 weeks, titrate based on response. |
| Geriatric use | Initial dose 6.25-12.5 mg IM/SC every 2-4 weeks; use lowest effective dose due to increased sensitivity to extrapyramidal effects and hypotension. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROLIXIN DECANOATE (PROLIXIN DECANOATE).
| Breastfeeding | Fluphenazine is excreted into human breast milk in small amounts. The milk-to-plasma (M/P) ratio is approximately 0.1–0.5. Relative infant dose is estimated at <2% of maternal weight-adjusted dose. A decision to breastfeed should consider the benefits of breastfeeding, the mother's need for medication, and potential adverse effects on the infant (drowsiness, irritability, poor feeding). Monitor infant for extrapyramidal symptoms and sedation. |
| Teratogenic Risk | Fluphenazine decanoate is classified as FDA Pregnancy Category C. First trimester: Limited human data, but potential risk of congenital malformations based on animal studies; second and third trimesters: Risk of extrapyramidal symptoms and/or withdrawal symptoms in neonates, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder. Exposure near term may result in neonatal jaundice and prolonged QT interval. Overall, risk must be weighed against benefit of treating maternal psychosis. |
■ FDA Black Box Warning
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Fluphenazine decanoate is not approved for the treatment of dementia-related psychosis.
| Serious Effects |
["Hypersensitivity to fluphenazine or any phenothiazine","Comatose states or severe CNS depression","Subcortical brain damage","Circulatory collapse","Concurrent use of large doses of CNS depressants (e.g., alcohol, barbiturates)"]
| Precautions | ["Tardive dyskinesia: risk increases with duration of therapy and cumulative dose","Neuroleptic malignant syndrome: discontinue immediately if symptoms occur","QT prolongation: caution in patients with risk factors for arrhythmias","Leukopenia, neutropenia, and agranulocytosis: monitor CBCs","Orthostatic hypotension: use with caution in patients with cardiovascular disease","Seizure threshold lowering: caution in patients with seizure disorders","Hepatic impairment: may require dose adjustment"] |
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| Fetal Monitoring | Maternal: Monitor blood pressure (orthostatic hypotension), ECG for QT prolongation, liver function tests, and signs of tardive dyskinesia. Fetal/neonatal: Monitor for extrapyramidal symptoms, sedation, jaundice, and withdrawal syndrome after delivery. Consider umbilical cord blood levels and neonatal ECG if maternal QT prolongation present. |
| Fertility Effects | Fluphenazine can cause hyperprolactinemia via dopamine D2 receptor blockade in the pituitary, leading to menstrual irregularities, anovulation, galactorrhea, and impaired spermatogenesis. These effects are reversible upon discontinuation. Fertility may be reduced during therapy. Women of childbearing potential should be counseled about contraceptive options due to potential harm to fetus. |