BLACK BOX WARNING
- increased mortality in elderly patients with dementia-related psychosis
fluphenazine
Brand: Prolixin
⚠ BBW Beers Criteria Prototype: haloperidol
Drug Class: first-generation antipsychotic (FGA)
Drug Family: antipsychotic
Subclass: high-potency phenothiazine
Organ Systems: cns
Mechanism of Action
High-potency D2 receptor antagonist with tight D2 binding and minimal alpha-1, H1, or muscarinic receptor affinity, resulting in more EPS but less sedation and orthostatic hypotension than low-potency phenothiazines. Available as long-acting decanoate depot injection for adherence-challenged patients.
D2 dopamine receptor
Indications
- schizophrenia
- off-label: Tourette syndrome
Contraindications
- subcortical brain damage
- blood dyscrasias
- hepatic impairment
Adverse Effects
Common
- extrapyramidal symptoms (high rate)
- akathisia
- hyperprolactinemia
Serious
- tardive dyskinesia
- NMS
- acute dystonia
Pharmacokinetics (ADME)
| Absorption | oral bioavailability variable; IM decanoate provides sustained release over 2-4 weeks |
| Distribution | highly lipophilic; protein binding ~91-99% |
| Metabolism | hepatic via CYP2D6 |
| Excretion | renal and biliary |
| Half-life | 10-20 hours (oral); 6.8-9.6 days (decanoate) |
| Onset | oral: within hours; decanoate: 24-72 hours with peak effect at 48-96 hours |
| Peak | 2-4 hours (oral); 24-72 hours (decanoate) |
| Duration | oral: 6-8 hours; decanoate: 2-4 weeks |
| Protein Binding | 91-99% |
| Vd | not well characterized |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| CNS depressants | additive sedation | moderate |
| anticholinergics | additive anticholinergic effects; may mask EPS | moderate |
Nursing Considerations
- Fluphenazine decanoate is a long-acting depot injection given every 2-4 weeks; this improves medication adherence in patients who cannot reliably take daily oral medication.
- EPS risk is highest among all phenothiazines due to high D2 binding affinity; have anticholinergic agents (benztropine, diphenhydramine) available for acute dystonic reactions.
- Assess for akathisia at every visit: patients experience an overwhelming urge to move, which can be mistaken for psychotic agitation and incorrectly prompt dose increases.
- Monitor for tardive dyskinesia at every visit using AIMS scale; this risk accumulates over months to years of treatment and may be irreversible.
Clinical Pearls
- The development of fluphenazine decanoate as a long-acting injectable (LAI) represented a major advancement in managing schizophrenia in patients with poor medication adherence, which is the primary predictor of relapse.
- High-potency FGAs like fluphenazine and haloperidol cause more EPS but less sedation, orthostatic hypotension, and weight gain than low-potency agents — this allows for safer use in medically ill patients.
Safety Profile
Pregnancy use-with-caution
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.