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. |
| Molecular Weight | 549.73 |
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 | Limited human data; animal studies suggest risk. Use only if benefit outweighs risk. Risk of extrapyramidal symptoms in newborn. |
| 2nd trimester | Limited human data; monitor for maternal hypotension and fetal effects. Risk of extrapyramidal symptoms in newborn. |
| 3rd trimester | Avoid near term due to risk of extrapyramidal symptoms, jaundice, and hypotonia in neonate. Use only if clearly needed. |
Clinical note
CNS depressants may enhance sedative effects Can cause extrapyramidal symptoms and neuroleptic malignant syndrome.
| FDA category | Animal |
| Placental transfer | Crosses placenta; detected in cord blood. |
| Breastfeeding |
■ 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 |
Comatose statesCNS depressionBlood dyscrasiasLiver damagePheochromocytomaHypersensitivity to phenothiazines
| 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. |
Loading safety data…
| Excreted into breast milk in small amounts; monitor infant for sedation, extrapyramidal effects, and poor feeding. Consider benefits vs risks. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
| Food/Dietary | No specific food interactions. Avoid excessive alcohol consumption due to additive CNS depression. |
| Clinical Pearls | Fluphenazine decanoate is a long-acting antipsychotic for maintenance therapy in chronic schizophrenia. Monitor for extrapyramidal symptoms (EPS) including tardive dyskinesia, especially in elderly females. Administer deep IM injection into gluteal muscle using Z-track technique to prevent local irritation. Titrate dose gradually; onset of action is 24-72 hours with peak effect at 48-96 hours. Avoid concurrent use with other antipsychotics due to cumulative EPS risk. |
| Patient Advice | This medication is given as an injection every 2-4 weeks to help control symptoms of schizophrenia. · Do not stop the medication suddenly; missed doses can lead to relapse. · Report any involuntary muscle movements, stiffness, or restlessness immediately. · Avoid alcohol and CNS depressants as they may increase sedation. · Use caution when driving or operating machinery until you know how this medication affects you. · Stay hydrated and avoid overheating; this medication can impair temperature regulation. |