Fluphenazine (Prolixin)
FGA • Last reviewed 2025-09-26
General information
Fluphenazine is a high-potency phenothiazine antipsychotic available as oral tablets, oral solution, short-acting IM, and decanoate depot for schizophrenia treatment.
Depot formulation supports dosing every 2–4 weeks for adherence support. EPS risk is high; metabolic impact is low.
Hyperprolactinemia and tardive dyskinesia are notable long-term concerns.
Depot fluphenazine is one of the earliest LAIs and remains widely used in resource-limited settings despite higher EPS liability.
Dosing & administration
Oral: start 2.5–10 mg/day divided; maintenance 5–20 mg/day.
Decanoate: 12.5–25 mg IM every 2 weeks initially; maintenance 12.5–75 mg every 2–4 weeks.
Overlap oral for 1 week when initiating depot.
Oral to depot conversion
- 10 mg/day oral
- 12.5 mg decanoate q3 weeks
- 20 mg/day oral
- 25 mg decanoate q3 weeks
- 30 mg/day oral
- 37.5 mg decanoate q3 weeks
Mechanism of action
Fluphenazine is a potent D2 receptor antagonist, reducing positive psychotic symptoms but increasing EPS risk.
Weak anticholinergic and antihistaminic effects yield modest sedation.
Metabolism & pharmacokinetics
Drug interactions
CYP2D6 inhibitors increase levels; reduce dose.
CNS depressants increase sedation.
Anticholinergics may reduce efficacy at high doses.
QT-prolonging drugs increase torsades risk.
| Mechanism | Agents / factors | Management |
|---|---|---|
| CYP2D6 inhibition | Fluoxetine, paroxetine | Reduce dose; monitor EPS |
| CNS depression | Benzodiazepines, opioids | Monitor sedation |
| QT prolongation | Macrolides, antiarrhythmics | Avoid |
Monitoring & safety checks
EPS/tardive dyskinesia
Each visit; AIMS q3–6 months • High EPS risk
Prolactin symptoms
Periodic • Hyperprolactinemia
Weight/metabolic labs
Baseline, annually • Metabolic monitoring
Injection site
Each depot dose • Monitor for nodules/pain
Educate on tardive dyskinesia; consider switching if early symptoms appear.
Track depot injection dates and adherence.
Discontinuation guidance
Gradually taper; extend depot interval prior to discontinuation.
Adverse effects
Common: EPS, akathisia, dystonia, sedation.
Serious: tardive dyskinesia, neuroleptic malignant syndrome, QT prolongation.
References
- Fluphenazine decanoate prescribing information — DailyMed (2024)
- Improving patient outcomes with depot antipsychotics — Schizophrenia Research (2011) DOI: 10.1016/S0920-9964(10)70291-8
- The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia — American Psychiatric Association (2020)
Educational use only — verify details in current prescribing information and authoritative clinical guidelines before making prescribing decisions.