Usage
Fluphenazine is prescribed for the management of manifestations of psychotic disorders, primarily schizophrenia. It is also used to treat severe anxiety, tension states, and personality disorders. It belongs to the pharmacological classification of typical antipsychotics (also known as neuroleptics or major tranquilizers). Fluphenazine works by blocking dopamine D1 and D2 receptors in the brain, reducing the excessive dopamine activity associated with psychotic symptoms.
Alternate Names
Fluphenazine is also known as fluphenazine hydrochloride or fluphenazine decanoate depending upon the formulation. It is marketed under various brand names, including Prolixin and Modecate.
How It Works
Pharmacodynamics: Fluphenazine primarily acts as a dopamine D1 and D2 receptor antagonist in the brain. This action decreases dopamine neurotransmission, which is thought to be responsible for the antipsychotic effects. Fluphenazine also exhibits anticholinergic, antihistaminic, and alpha-adrenergic blocking properties, contributing to some of its side effects.
Pharmacokinetics:
- Absorption: Oral fluphenazine is rapidly absorbed from the gastrointestinal tract. The bioavailability is variable. Intramuscular administration provides more predictable absorption. Fluphenazine decanoate, a long-acting formulation, is administered intramuscularly or subcutaneously and forms a depot, from which it is slowly released over several weeks.
- Metabolism: Fluphenazine is extensively metabolized in the liver by CYP450 enzymes, primarily CYP2D6.
- Elimination: Fluphenazine and its metabolites are primarily eliminated in the urine and to a lesser extent in feces.
Mode of Action: Fluphenazine binds to and blocks dopamine D1 and D2 receptors, predominantly in the mesolimbic and mesocortical pathways of the brain, reducing dopaminergic neurotransmission and ameliorating positive symptoms of psychosis (hallucinations, delusions, and disorganized thinking).
Elimination Pathways: Fluphenazine is extensively metabolized in the liver via CYP450 enzymes, notably CYP2D6. Metabolites and unchanged drug are excreted primarily through the kidneys and, to a lesser extent, via biliary excretion into the feces.
Dosage
Standard Dosage
Adults:
- Oral: Initial dose: 2.5-10 mg/day, divided every 6-8 hours. Maintenance dose: 1-5 mg/day, often as a single dose. Maximum dose: 40 mg/day (doses above 20 mg/day should be used cautiously, and efficacy and safety beyond 40 mg are not established).
- Intramuscular (Fluphenazine Hydrochloride): Initial dose: 1.25 mg, then 2.5-10 mg/day divided every 6-8 hours (doses above 10 mg/day should be used cautiously). Switch to oral therapy when possible.
- Intramuscular (Fluphenazine Decanoate): Initial dose: 12.5-25 mg. Maintenance dose: 12.5-100 mg every 2-5 weeks (typically every 3-4 weeks), Maximum dose: 100 mg/injection.
Children: Fluphenazine is not generally recommended for children. There is limited data to guide pediatric dosing, and alternative antipsychotics with better-established safety profiles are typically preferred.
Special Cases:
- Elderly Patients: Initiate at a lower dose (1-2.5 mg/day orally or 6.25 mg IM for decanoate) and titrate cautiously due to increased sensitivity to extrapyramidal side effects.
- Patients with Renal Impairment: Use with caution and monitor closely. Dose adjustments might be required based upon creatinine clearance values.
- Patients with Hepatic Dysfunction: Use with caution and monitor liver function tests closely. Dose adjustment might be needed.
- Patients with Comorbid Conditions: Exercise caution in individuals with cardiovascular disease, epilepsy, diabetes, or other conditions. Careful monitoring and potential dose modifications might be needed.
Clinical Use Cases
Fluphenazine is generally not indicated for use in procedures like intubation, surgical settings, or during mechanical ventilation. Its primary role is in the management of psychotic disorders. For sedation in such procedures, short-acting medications like benzodiazepines or other sedative agents are preferred. Fluphenazine might be used in the ICU for managing acute psychotic exacerbations, but careful consideration of potential drug interactions and side effects is crucial. For emergencies involving psychosis-related agitation or aggression, intramuscular fluphenazine hydrochloride can be employed.
Dosage Adjustments
Dosage adjustments should be made based on patient response, tolerability, and clinical status. Monitor closely for side effects, particularly extrapyramidal symptoms. Consider therapeutic drug monitoring in some cases. Dose modifications are necessary for renal or hepatic impairment, comorbid conditions, and interacting medications.
Side Effects
Common Side Effects:
Sedation, dizziness, dry mouth, blurred vision, constipation, urinary retention, orthostatic hypotension, extrapyramidal symptoms (dystonia, akathisia, parkinsonism), weight gain.
Rare but Serious Side Effects:
Neuroleptic malignant syndrome (NMS), tardive dyskinesia, agranulocytosis, seizures, severe hypotension, cardiac arrhythmias (including QT prolongation), liver dysfunction.
Long-Term Effects:
Tardive dyskinesia (a movement disorder), metabolic syndrome (weight gain, dyslipidemia, hyperglycemia), sexual dysfunction.
Adverse Drug Reactions (ADR):
NMS, agranulocytosis, severe hypotension, cardiac arrhythmias, anaphylaxis.
Contraindications
Comatose states, CNS depression, subcortical brain damage, severe cardiovascular disease, blood dyscrasias, liver failure, hypersensitivity to fluphenazine.
Drug Interactions
Drugs that prolong the QT interval (e.g., some antibiotics, antiarrhythmics), CNS depressants (e.g., alcohol, benzodiazepines, opioids), anticholinergic drugs, CYP2D6 inhibitors or inducers.
Pregnancy and Breastfeeding
Pregnancy Safety Category C. Fluphenazine can cross the placenta and may cause extrapyramidal symptoms or withdrawal symptoms in neonates. Use during pregnancy only if the potential benefit outweighs the risk to the fetus. Fluphenazine is excreted in breast milk and may cause adverse effects in nursing infants. Breastfeeding is generally not recommended.
Drug Profile Summary
- Mechanism of Action: Dopamine D1 and D2 receptor antagonist.
- Side Effects: Sedation, extrapyramidal symptoms, tardive dyskinesia, NMS, metabolic effects.
- Contraindications: Comatose states, CNS depression, severe cardiovascular disease, liver failure.
- Drug Interactions: QT prolonging drugs, CNS depressants, anticholinergics, CYP2D6 inhibitors/inducers.
- Pregnancy & Breastfeeding: Category C; use with caution; breastfeeding not recommended.
- Dosage: See detailed dosage section above.
- Monitoring Parameters: Extrapyramidal symptoms, weight, blood glucose, lipids, liver function tests, complete blood count, ECG (in some patients).
Popular Combinations
Fluphenazine is sometimes used in combination with other psychotropic medications, such as antidepressants or mood stabilizers, to address specific symptom clusters or comorbid psychiatric conditions.
Precautions
Close monitoring is essential, particularly at the start of treatment and with dose increases. Pre-screening should assess cardiovascular health, liver and kidney function, and history of seizures or blood disorders. Caution is advised in elderly patients, pregnant/breastfeeding women, and patients with pre-existing medical conditions. Avoid alcohol and other CNS depressants. Monitor for suicidal ideation.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Fluphenazine?
A: See the detailed dosage section above, as it varies depending on the formulation (oral, IM hydrochloride, IM decanoate), patient characteristics (adult, elderly, renal/hepatic impairment), and clinical context.
Q2: What are the most common side effects of Fluphenazine?
A: Common side effects include sedation, dizziness, dry mouth, blurred vision, constipation, urinary retention, orthostatic hypotension, and extrapyramidal symptoms (dystonia, akathisia, parkinsonism).
A: Serious side effects include neuroleptic malignant syndrome (NMS), tardive dyskinesia, agranulocytosis, seizures, and severe cardiac effects (e.g., QT prolongation, arrhythmias).
Q4: What are the contraindications for using Fluphenazine?
A: Contraindications include comatose states, severe CNS depression, known hypersensitivity to fluphenazine, subcortical brain damage, severe cardiovascular disease, blood dyscrasias, and liver failure.
Q5: Can Fluphenazine be used during pregnancy or breastfeeding?
A: Fluphenazine is Pregnancy Safety Category C, meaning it should only be used during pregnancy if the potential benefits outweigh the risks to the fetus. Its use during breastfeeding is generally not recommended due to potential harm to the infant.
Q6: What are the key drug interactions to be aware of with Fluphenazine?
A: Important drug interactions involve agents that prolong the QT interval, CNS depressants, anticholinergics, and CYP2D6 inhibitors or inducers.
Q7: How is Fluphenazine metabolized and eliminated from the body?
A: Fluphenazine is primarily metabolized in the liver by CYP450 enzymes, particularly CYP2D6. Metabolites and the parent drug are eliminated mainly in the urine and to a lesser extent in the feces.
Q8: What monitoring parameters are important for patients receiving Fluphenazine?
A: Monitor for extrapyramidal side effects, changes in weight, blood glucose and lipid levels, liver function, complete blood count, and ECG (in high-risk individuals).
Q9: What patient education should be provided to someone starting Fluphenazine?
A: Patients should be advised about potential side effects, including extrapyramidal symptoms, sedation, and metabolic effects. Emphasize the importance of adherence to the prescribed regimen, avoidance of alcohol and other CNS depressants, and reporting any concerning symptoms to their healthcare provider.
