Fluphenazine - Drug Monograph

Introduction

Fluphenazine is a first-generation (typical) antipsychotic medication belonging to the phenothiazine class. It is primarily used in the management of psychotic disorders, particularly schizophrenia. Available in both oral and long-acting injectable formulations, fluphenazine has been a cornerstone of psychiatric treatment since its introduction in the 1950s.

Mechanism of Action

Fluphenazine exerts its antipsychotic effects primarily through potent antagonism of dopamine D2 receptors in the mesolimbic pathway of the brain. This action reduces positive symptoms of psychosis such as hallucinations, delusions, and disorganized thinking. The drug also demonstrates antagonism at alpha-1 adrenergic, histaminic H1, and muscarinic cholinergic receptors, contributing to both its therapeutic effects and side effect profile.

Indications

• Treatment of psychotic disorders, particularly schizophrenia
• Management of psychotic features associated with other psychiatric conditions
• Off-label uses may include acute agitation, Tourette's syndrome, and severe behavioral disturbances (though other agents are typically preferred)

Dosage and Administration

• Initial dose: 2.5-10 mg daily in divided doses
• Maintenance: 1-5 mg daily (may be given as single daily dose)
• Maximum dose: Generally not to exceed 40 mg daily

• Initial dose: 12.5-25 mg IM every 2-4 weeks
• Maintenance: 12.5-100 mg every 2-6 weeks
• Dose conversion: Approximately 10-20 times the previous daily oral dose

• Geriatric patients: Start with lower doses (1-2.5 mg daily)
• Hepatic impairment: Use with caution and reduce dosage
• Renal impairment: No specific dosage adjustment recommended, but use cautiously

Pharmacokinetics

Contraindications

• Hypersensitivity to phenothiazines
• Severe central nervous system depression or comatose states
• Blood dyscrasias
• Significant hepatic impairment
• Concomitant use with high-dose antipsychotics or other agents that prolong QT interval

Warnings and Precautions

• Black Box Warning: Increased mortality in elderly patients with dementia-related psychosis
• Risk of tardive dyskinesia (often irreversible)
• Neuroleptic malignant syndrome (potentially fatal)
• QT prolongation and risk of torsades de pointes
• Orthostatic hypotension
• Seizure threshold lowering
• Extrapyramidal symptoms (pseudoparkinsonism, akathisia, dystonia)
• Hyperprolactinemia
• Temperature regulation dysfunction

Drug Interactions

• CNS depressants: Enhanced sedation with alcohol, benzodiazepines, opioids
• Anticholinergics: May reduce efficacy and increase side effects
• Enzyme inducers/inhibitors: CYP2D6 inhibitors (fluoxetine, paroxetine) may increase levels; inducers (carbamazepine) may decrease levels
• Antihypertensives: Potentiated hypotensive effects
• QT-prolonging agents: Additive risk with other antipsychotics, antiarrhythmics, antibiotics

Adverse Effects

• Extrapyramidal symptoms
• Sedation
• Dry mouth
• Blurred vision
• Constipation

• Tardive dyskinesia
• Neuroleptic malignant syndrome
• Agranulocytosis
• Seizures
• Cardiac arrhythmias
• Severe orthostatic hypotension

Monitoring Parameters

• Efficacy: Psychiatric symptom assessment using standardized scales
• Safety: Regular assessment for extrapyramidal symptoms and tardive dyskinesia (AIMS exam every 6 months)
• Metabolic: Weight, BMI, blood glucose, lipid profile at baseline and periodically
• Cardiac: ECG for QT prolongation at baseline and with dose changes
• Hematologic: CBC at baseline and with symptoms of infection
• Prolactin: Levels if symptomatic hyperprolactinemia suspected

Patient Education

• Take medication as prescribed; do not stop abruptly
• Rise slowly from sitting/lying positions to prevent dizziness
• Avoid alcohol and other CNS depressants
• Report any unusual movements, muscle stiffness, or fever immediately
• Use caution when driving or operating machinery until effects are known
• Maintain regular follow-up appointments for monitoring
• Inform all healthcare providers about fluphenazine use
• Use effective contraception due to potential effects on fertility and pregnancy

References

1. American Psychiatric Association. (2020). The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. 2. Lehne, R. A. (2013). Pharmacology for Nursing Care. Elsevier Health Sciences. 3. Fluphenazine hydrochloride prescribing information. FDA. 4. Kane, J. M., et al. (2019). Clinical Guidance on the Identification and Management of Treatment-Resistant Schizophrenia. Journal of Clinical Psychiatry. 5. Marder, S. R., & Cannon, T. D. (2019). Schizophrenia. New England Journal of Medicine. 6. Miller, D. D., & Caroff, S. N. (2020). Neuroleptic Malignant Syndrome. JAMA Psychiatry.