Last reviewed 2026-04-20 · How we verify

Prolixin (FLUPHENAZINE)

Prolixin (fluphenazine) is a phenothiazine antipsychotic medication originally developed by Smith, Kline & French. It is a small molecule that targets the D(3) dopamine receptor, and was first approved by the FDA in 1959 for the treatment of psychotic disorders and schizophrenia. Prolixin is now off-patent and has multiple generic manufacturers. The medication has a relatively long half-life of 12.3 hours and low bioavailability of 3%. It is currently owned by Apothecon.

At a glance

Approved indications

• Psychotic disorder
• Schizophrenia

Boxed warnings

• Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Fluphenazine Hydrochloride Oral Solution USP (Concentrate) is not approved for the treatment of patients with dementia-related psychosis ( see WARNINGS ).

Common side effects

• Neuroleptic malignant syndrome
• Salivary hypersecretion
• Priapism
• Torsade de pointes
• Sedation
• Compartment syndrome
• Parkinsonism
• Suicide attempt
• Extrapyramidal disorder
• Rhabdomyolysis
• Blood prolactin increased
• Embolism venous

Drug interactions

• cabergoline
• entacapone
• levodopa
• pergolide
• pramipexole
• ropinirole

Key clinical trials

• Long-acting Injectable Antipsychotics for Mental Ill-Health in Pregnancy and Postpartum
• A Study to Assess Stroke Risk Among Users of Typical Versus Atypical Antipsychotics Stratified by Broad Age Group
• Antipsychotic Induced Structural and Functional Brain Changes (PHASE4)
• New Antipsychotic Strategies: Quetiapine and Risperidone vs. Fluphenazine in Treatment Resistant Schizophrenia (PHASE3)
• Family Intervention in Recent Onset Schizophrenia Treatment (FIRST)
• Reducing Antipsychotic-Induced Weight Gain in Children With Metformin (PHASE1)
• Evaluation of the Necessity of Long-term Pharmacological Treatment With Antipsychotics in Schizophrenic Patients (PHASE4)
• Efficacy and Safety of Fosaprepitant Dimeglumine in Preventing Chemotherapy-Induced Nausea and Vomiting (MK-0517-031) (PHASE3)

Primary sources

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