fluphenazine
Last reviewed 2025-12-29
Reviewed by PsychMed Editorial Team.
Brands: Prolixin
Sources updated 2024 • 5 references
General Information
Fluphenazine is a high-potency first-generation antipsychotic (FGA) available in oral and depot formulations for schizophrenia maintenance, offering potent D2 blockade with minimal metabolic burden.
Depot fluphenazine decanoate remains a cost-effective option when long-acting coverage is needed and extrapyramidal risk can be managed.
The compare view and fluphenazine evidence feed can help contrast EPS liability, metabolic effects, and LAI intervals when switching depot strategies.
Depot planning can be supported by the LAI Navigator and the schizophrenia hub; injection counseling can be shared via the fluphenazine print page.
Best suited to patients who have previously responded to FGAs and can engage in routine movement-disorder monitoring; generally avoided for behavioral symptoms in dementia, and therapy is reassessed if tardive dyskinesia emerges.
U.S. approvals
- Schizophrenia (oral/injectable) (1959)
Formulations & strengths
- Oral tablets 1–10 mg, oral elixir 2.5 mg/5 mL, lactate injection 2.5 mg/mL, decanoate depot 25 mg/mL (IM every 2–4 weeks).
Generic availability
- All formulations available generically.
Used for maintenance in resource-limited settings and for patients responsive to typical antipsychotics; EPS prophylaxis and tardive dyskinesia monitoring are key safety considerations.
View labelExactMechanism of Action
Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.
High-affinity antagonist at dopamine D2 receptors suppressing psychotic symptoms while increasing extrapyramidal risk.
Limited serotonergic antagonism and minimal histaminergic or muscarinic blockade produce lower sedation and anticholinergic burden than low-potency FGAs.
- Strong antagonist at dopamine D2 receptors.
- Mild antagonist at serotonin 5-HT2 receptors.
- Antagonist at adrenergic α1 receptors.
Metabolism and Pharmacokinetics
- Oral peak concentrations 1–3 h; decanoate hydrolyzed slowly with onset 12–24 h post injection.
- Metabolized hepatically via CYP2D6/CYP3A4 to inactive metabolites; half-life 15–30 h (oral) and ~7–10 days (depot).
- Depot kinetics vary by patient and injection interval; anticipate slower dose adjustments with decanoate and delayed-onset EPS monitoring is common after interval or dose changes.
Dosing and Administration
- Oral: typical start is 2.5–5 mg/day divided; titrate to 5–20 mg/day; rarely exceed 40 mg/day.
- Decanoate: typical initiation is 12.5–25 mg IM every 2 weeks with oral overlap; maintenance 12.5–50 mg IM every 2–4 weeks.
Monitoring & Labs
- Baseline and ongoing EPS monitoring (SAS/Barnes scales when available) and AIMS screening (often every 3–6 months) for tardive dyskinesia.
- Weight/BMI and metabolic labs periodically even with lower metabolic liability, because overall cardiometabolic risk remains important in schizophrenia care.
- Orthostatic vitals and falls risk during titration and after depot dose or interval changes; adjunctive medications are reviewed accordingly.
- Prolactin-related symptoms (sexual dysfunction, amenorrhea, galactorrhea) and overall functioning—consider switching if persistent.
- ECG monitoring in cardiac disease, electrolyte abnormalities, high-dose therapy, or when combining with QT-active medications.
- Depot adherence and injection-site assessments at each visit; review missed-dose plans and clinic access reliability.
- Counseling often covers rare emergencies (NMS, severe dystonia, allergic reactions) and when to seek urgent care.
Monitoring prioritizes movement disorders and depot logistics; the LAI format can improve adherence but also makes side effects slower to reverse, so early detection matters.
Adverse Effects
FDA boxed warnings
- Increased mortality in elderly patients with dementia-related psychosis.
Common side effects (≥10%)
- Extrapyramidal symptoms: >30% without prophylaxis; anticholinergic coverage is often considered during initiation, and EPS monitoring is common early.
- Tardive dyskinesia: Risk increases with cumulative exposure; routine monitoring often uses AIMS assessments.
- Hyperprolactinemia: Galactorrhea, amenorrhea, gynecomastia due to potent D2 blockade—counseling often covers prolactin symptoms.
- Sedation: Less than low-potency agents but present.
- Orthostatic hypotension: From α1 antagonism.
Other notable effects
- QTc monitoring is often considered at high doses or with IV use; torsades reported rarely.
- Neuroleptic malignant syndrome possible; counseling often covers early signs.
Interactions
Other Useful Information
- AIMS assessments are commonly used to detect tardive dyskinesia early.
- Counseling often covers EPS symptoms; rescue medications may be used (e.g., benztropine).
- Metabolic labs are still commonly obtained despite lower metabolic risk.
- For depot therapy, a written injection schedule, site rotation, and a missed-dose plan are commonly used to reduce relapse risk.
- Prolactin-related symptoms and sexual side effects are often discussed; switching options are revisited if quality of life declines.
References
- Fluphenazine decanoate prescribing information — DailyMed (2024)
- Triple advantages of injectable long acting second generation antipsychotics: relapse prevention, neuroprotection, and lower mortality — Schizophrenia Research (2018)
- Ravaris1973 Fluphenazine Placebo
- The CANMAT and ISBD Guidelines for the Management of Patients With Bipolar Disorder: 2021 Update — Bipolar Disorders (2021)Guidelinebipolarclinical