PROLIXIN ENANTHATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROLIXIN ENANTHATE (PROLIXIN ENANTHATE).
Fluphenazine (the active entity of PROLIXIN ENANTHATE) is a phenothiazine antipsychotic that blocks postsynaptic dopamine D1 and D2 receptors in the mesolimbic and mesocortical pathways. It also exhibits alpha-adrenergic blocking and anticholinergic effects.
| Metabolism | Hepatic metabolism via CYP2D6, glucuronidation, and sulfoxidation; extensive first-pass metabolism; inactive and active metabolites (e.g., 7-hydroxyfluphenazine); elimination half-life approximately 14 days (enanthate ester). |
| Excretion | Primarily renal (30-40% as metabolites, <1% unchanged) and biliary/fecal (15-20%) |
| Half-life | Terminal elimination half-life approximately 11-15 days due to slow release from intramuscular depot; requires monitoring for prolonged effects after discontinuation |
| Protein binding | 90-99% bound, primarily to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | Vd approximately 10-20 L/kg, indicating extensive tissue distribution and slow elimination |
| Bioavailability | Intramuscular: 100% (depot formulation with esterification); Oral: 40-50% due to first-pass metabolism; bioavailability of enanthate ester is essentially complete via IM route due to slow hydrolysis |
| Onset of Action | Intramuscular: 24-72 hours; Oral: 30-60 minutes for acute effects |
| Duration of Action | Intramuscular depot: 2-4 weeks for antipsychotic effect; Oral: 6-8 hours for sedation, but antipsychotic effects persist longer |
| Molecular Weight | 434.52 |
12.5-50 mg intramuscularly every 1-3 weeks. Initial dose: 2.5-12.5 mg IM as a test dose; gradual titration based on response and tolerability.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment guidance; use caution in severe renal impairment (CrCl <30 mL/min) due to potential for accumulation. Monitor for adverse effects. |
| Liver impairment | Child-Pugh Class A: No adjustment. Class B: Reduce dose by 50% or increase dosing interval. Class C: Avoid use or reduce dose by 75% with close monitoring. |
| Pediatric use | Not recommended for children <12 years. For adolescents 12-18 years: 0.1-0.3 mg/kg/dose IM every 2-4 weeks; maximum 25 mg/dose. Titrate based on response. |
| Geriatric use | Initiate at 2.5-5 mg IM, then increase slowly to 10-25 mg every 2-4 weeks; maximum 25 mg/dose. Monitor for hypotension, sedation, extrapyramidal symptoms, and anticholinergic effects. |
| 1st trimester | Fluphenazine enanthate is not recommended during the first trimester due to potential teratogenic effects; use only if clearly needed and benefit outweighs risk. |
| 2nd trimester | Limited data; may be used if necessary, but monitor for extrapyramidal symptoms and maternal hypotension. |
| 3rd trimester | Avoid use in the third trimester due to risk of neonatal extrapyramidal symptoms, jaundice, and prolonged QT interval; if used, taper near term. |
Clinical note
Comprehensive clinical and safety monograph for PROLIXIN ENANTHATE (PROLIXIN ENANTHATE).
| Placental transfer | Fluphenazine crosses the placenta; demonstrated in animal studies and inferred from human neonatal effects. |
| Breastfeeding | Fluphenazine is excreted into breast milk in low concentrations; potential for adverse effects in the infant including sedation, extrapyramidal symptoms, and impaired thermoregulation. Consider alternatives or monitor infant closely. |
■ FDA Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis. PROLIXIN ENANTHATE is not approved for the treatment of dementia-related psychosis.
| Serious Effects |
Comatose statesCNS depressionKnown hypersensitivity to fluphenazine or phenothiazinesSubcortical brain damageBlood dyscrasiasHepatic failure
| Precautions | Neuroleptic malignant syndrome (NMS), Tardive dyskinesia, QT prolongation and risk of arrhythmias, Hypotension, Seizures, Leukopenia/neutropenia/agranulocytosis, Hyperprolactinemia, Thrombotic thrombocytopenic purpura (TTP), Avoid abrupt withdrawal |
| Food/Dietary | Avoid alcohol. No specific food restrictions. Maintain adequate hydration; avoid excessive caffeine if experiencing tremor or agitation. Grapefruit and grapefruit juice have not been reported to interact significantly, but caution is advised with any CYP450 interactions. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited data, but risk of neural tube defects and cardiovascular anomalies cannot be excluded. Second/third trimesters: Risk of extrapyramidal symptoms, withdrawal, and neonatal adaptation syndrome with late exposure. Chronic use associated with persistent pulmonary hypertension of the newborn (PPHN). |
| Fetal Monitoring | Monitor maternal blood pressure, glucose, weight, and signs of EPS. Fetal ultrasound for growth and anomalies. Neonatal assessment for dyskinesia, feeding difficulties, and respiratory depression. |
| Fertility Effects | May cause hyperprolactinemia, leading to menstrual irregularities, anovulation, and reduced fertility in women. Reversible upon discontinuation. No direct effect on male fertility reported. |
| Clinical Pearls | PROLIXIN ENANTHATE (fluphenazine enanthate) is a long-acting depot antipsychotic for maintenance therapy in schizophrenia. Monitor for extrapyramidal symptoms (EPS), tardive dyskinesia, and neuroleptic malignant syndrome (NMS). Use with caution in patients with cardiovascular disease due to risk of QT prolongation. Avoid concurrent use with other CNS depressants. Administer deep IM injection into gluteal muscle; do not administer IV. Rotate injection sites. |
| Patient Advice | Take this medication exactly as prescribed by your doctor; it is usually given as an injection every 2-6 weeks. · Do not discontinue without consulting your doctor; sudden stoppage may cause withdrawal symptoms or worsening of your condition. · You may experience drowsiness, dizziness, or blurred vision; avoid driving or operating machinery until you know how this medication affects you. · Report any signs of infection, fever, muscle stiffness, confusion, or abnormal movements to your doctor immediately. · Avoid alcohol and other CNS depressants as they may increase side effects. · Stay hydrated and avoid overheating; this medication can affect your body's temperature regulation. · Inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding. · Carry a medical alert card or wear a bracelet indicating your use of this medication. |