PROLIXIN ENANTHATE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PROLIXIN ENANTHATE (PROLIXIN ENANTHATE).

How it works

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.

What the body does with it

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

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PROLIXIN ENANTHATE (PROLIXIN ENANTHATE).

Breastfeeding	Fluphenazine enanthate is excreted into breast milk in small amounts, estimated infant dose <1% of maternal weight-adjusted dose. M/P ratio not reported. Caution advised, monitor infant for sedation, hypotonia, and extrapyramidal signs.
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).

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to fluphenazine or any phenothiazine derivative","Comatose states","Substantial central nervous system depression","Severe hypotension","Pheochromocytoma","Concurrent use with high doses of CNS depressants"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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PROLIXIN ENANTHATE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PROLIXIN ENANTHATE (PROLIXIN ENANTHATE).

How it works

What the body does with it

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

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PROLIXIN ENANTHATE (PROLIXIN ENANTHATE).

Breastfeeding	Fluphenazine enanthate is excreted into breast milk in small amounts, estimated infant dose <1% of maternal weight-adjusted dose. M/P ratio not reported. Caution advised, monitor infant for sedation, hypotonia, and extrapyramidal signs.
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).

Warnings & precautions

■ 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.