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. |
| Molecular Weight | 510.42 |
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 | Use only if potential benefit justifies risk. Risk of extrapyramidal symptoms and withdrawal in neonate; isolated reports of limb reduction anomalies. |
| 2nd trimester | Use only if potential benefit justifies risk. Risk of neonatal extrapyramidal symptoms and withdrawal. |
| 3rd trimester | Avoid in third trimester due to risk of neonatal extrapyramidal symptoms, withdrawal, and possible prolonged QT interval. |
Clinical note
Comprehensive clinical and safety monograph for PROLIXIN DECANOATE (PROLIXIN DECANOATE).
| Placental transfer | Fluphenazine crosses the placenta; detectable in cord blood and amniotic fluid. Degree of transfer is moderate but variable. |
| Breastfeeding | Fluphenazine decanoate is excreted into breast milk in small amounts. Monitor infant for drowsiness, irritability, and abnormal movements. American Academy of Pediatrics considers use compatible with breastfeeding. |
■ 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 componentComatose statesCentral nervous system depressionSubcortical damageBlood dyscrasiasHepatic diseasePheochromocytoma
| 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 |
| Food/Dietary | No specific food-drug interactions. Avoid excessive caffeine or grapefruit juice as they may theoretically affect metabolism, but evidence is lacking. Maintain adequate hydration to avoid hypotension. No dietary restrictions required. |
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| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
| Clinical Pearls | Prolixin Decanoate (fluphenazine decanoate) is a long-acting injectable antipsychotic used for maintenance therapy in schizophrenia. Administer deep intramuscularly only; do not administer intravenously or subcutaneously. Rotate injection sites to reduce the risk of sterile abscesses. Monitor for extrapyramidal symptoms (EPS), especially akathisia and tardive dyskinesia; consider prophylactic anticholinergic agents. Due to its long half-life (6-9 days), adverse effects may be prolonged. Neuroleptic malignant syndrome (NMS) is a rare but life-threatening emergency; watch for fever, rigidity, autonomic instability. Baseline ECG, liver function, and CBC are recommended. Avoid concurrent use with CNS depressants, including alcohol. Also monitor for QT prolongation, especially in patients with electrolyte disturbances or on other QT-prolonging drugs. Orthostatic hypotension may occur; advise patients to rise slowly from sitting or lying positions. |
| Patient Advice | This medication is given as an injection every 2-4 weeks; it controls psychotic symptoms but does not cure them. · Do not stop the medication suddenly; sudden discontinuation may cause withdrawal symptoms or relapse. · Avoid alcohol and other CNS depressants (e.g., benzodiazepines, opioids) as they can increase drowsiness and respiratory depression. · Report any muscle stiffness, restlessness, uncontrollable movements, or fever immediately. · Rise slowly from sitting or lying down to prevent dizziness from low blood pressure. · Contact your doctor if you experience blurred vision, difficulty urinating, rapid heartbeat, or jaundice (yellowing of skin/eyes). · Use sunscreen and protective clothing as this medication may increase sensitivity to sunlight. · Keep all appointments for injections and follow-up blood work. |