FLUPHENAZINE DECANOATE
Clinical safety rating: safe
CNS depressants may enhance sedative effects Can cause extrapyramidal symptoms and neuroleptic malignant syndrome.
Fluphenazine decanoate is a long-acting phenothiazine antipsychotic. It exerts its effects by blocking postsynaptic dopamine D2 receptors in the mesolimbic pathway, and also has antagonistic activity at alpha-1 adrenergic, muscarinic, and histamine H1 receptors, contributing to its side effect profile.
| Metabolism | Fluphenazine decanoate is an ester prodrug that is slowly hydrolyzed to fluphenazine. Fluphenazine undergoes extensive hepatic metabolism via oxidation, hydroxylation, and conjugation; major CYP450 isoenzymes involved include CYP2D6, with minor contributions from CYP1A2 and CYP3A4. |
| Excretion | Primarily renal (metabolites) and fecal (biliary). Estimated 50% renal, 50% fecal as metabolites. |
| Half-life | Terminal elimination half-life is approximately 14 days (range 7-21 days) following IM injection, reflecting slow release from depot and prolonged redistribution. |
| Protein binding | Approximately 99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Large: 9-20 L/kg (mean ~13 L/kg). Indicates extensive tissue binding and redistribution. |
| Bioavailability | IM depot: 100% (only available as long-acting injectable). Oral: 2.5% (not used clinically). |
| Onset of Action | IM depot: 24-72 hours, with peak effects at 48-96 hours. |
| Duration of Action | IM depot: 3-4 weeks. Clinical effect may persist for up to 6 weeks due to slow release from muscle depot. |
12.5-25 mg deep IM injection every 2-4 weeks, not exceeding 100 mg per dose.
| Dosage form | INJECTABLE |
| Renal impairment | No adjustment required for GFR >10 mL/min; avoid use in GFR <10 mL/min due to risk of accumulation. |
| Liver impairment | Child-Pugh A: start at 12.5 mg IM every 4 weeks; Child-Pugh B: 12.5 mg IM every 4 weeks with slow titration; Child-Pugh C: contraindicated. |
| Pediatric use | Not recommended for children <12 years; adolescents: 6.25-12.5 mg IM every 2-4 weeks, titrate slowly. |
| Geriatric use | Initial dose 2.5-6.25 mg IM every 2-4 weeks; maximum 50 mg per dose; monitor for extrapyramidal symptoms and hypotension. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants may enhance sedative effects Can cause extrapyramidal symptoms and neuroleptic malignant syndrome.
| FDA category | Animal |
| Breastfeeding | Fluphenazine is excreted in breast milk; M/P ratio unknown. Monitor infant for sedation, extrapyramidal symptoms, impaired thermoregulation, and poor feeding. The American Academy of Pediatrics recommends caution. Use lowest effective dose if breastfeeding. |
| Teratogenic Risk | First trimester: Limited data; potential risk of congenital malformations (loop-like defect, neural tube defects) cannot be excluded. Second/third trimester: Risk of extrapyramidal symptoms, withdrawal symptoms (hypertonia, hypotonia, tremor, somnolence, respiratory distress, feeding disorder) in neonates. No well-controlled studies; use only if benefit outweighs risk. |
■ FDA Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis. Antipsychotic drugs are not approved for the treatment of dementia-related psychosis.
| Common Effects | Extrapyramidal symptoms |
| Serious Effects |
["Hypersensitivity to fluphenazine or any phenothiazine derivative","Comatose states or severe CNS depression (e.g., barbiturate, alcohol, or narcotic intoxication)","History of blood dyscrasias (e.g., agranulocytosis) related to phenothiazine use","Known subcortical brain damage with or without hypothalamic damage (e.g., prior to stereotactic surgery)"]
| Precautions | ["Tardive dyskinesia: risk increases with cumulative dose and treatment duration. Discontinue if signs/symptoms appear.","Neuroleptic malignant syndrome (NMS): potentially fatal, characterized by hyperthermia, muscle rigidity, autonomic instability, and altered mental status. Discontinue immediately and initiate intensive monitoring.","QT prolongation: increased risk of cardiac arrhythmias; use caution with concomitant QT-prolonging drugs, electrolyte disturbances, or underlying cardiac disease.","Seizures: may lower seizure threshold; use cautiously in patients with epilepsy or predisposing factors.","Hypotension and orthostatic hypotension: especially during intramuscular injection; monitor blood pressure and advise patients to rise slowly."] |
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| Fetal Monitoring | Monitor maternal vital signs, EPS, and mental status. Fetal assessment: serial ultrasounds for growth and anatomy; neonatal monitoring for EPS, withdrawal, and neurobehavioral effects after delivery. |
| Fertility Effects | May increase prolactin levels via dopamine receptor blockade, potentially causing galactorrhea, amenorrhea, anovulation, and impaired fertility in females. In males, may cause erectile dysfunction, ejaculatory dysfunction, and decreased libido. Effects are reversible upon discontinuation. |