Usage
- Medical Conditions: Trifluoperazine is prescribed for the treatment of psychotic disorders like schizophrenia, and for short-term management of non-psychotic anxiety when other medications (like benzodiazepines) haven’t been effective. It can also be used to treat nausea and vomiting.
- Pharmacological Classification: Trifluoperazine is a first-generation (typical) antipsychotic medication, belonging to the phenothiazine class.
- Mechanism of Action: Trifluoperazine primarily acts as a dopamine receptor antagonist, specifically blocking D2 receptors in the brain. This action helps reduce the excessive dopamine activity associated with psychotic symptoms.
Alternate Names
- Generic Name: Trifluoperazine hydrochloride
- Brand Name: Stelazine (discontinued in some regions, available as generic)
How It Works
- Pharmacodynamics: Trifluoperazine exerts its antipsychotic effects by blocking D2 dopamine receptors in the mesolimbic and mesocortical pathways of the brain. It also has some affinity for other receptors, including alpha-adrenergic, histamine H1, and muscarinic receptors, which contribute to its side effect profile.
- Pharmacokinetics:
- Absorption: Well-absorbed orally.
- Metabolism: Extensively metabolized in the liver, primarily via CYP450 enzymes.
- Elimination: Excreted in urine and feces.
- Mode of Action: By blocking D2 receptors, Trifluoperazine reduces dopaminergic neurotransmission, alleviating positive symptoms of schizophrenia (e.g., hallucinations, delusions). Its effects on other receptor systems contribute to side effects such as sedation (histamine H1 blockade), dry mouth (muscarinic blockade), and orthostatic hypotension (alpha-adrenergic blockade).
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Primarily a D2 receptor antagonist. Also affects alpha-adrenergic, histamine H1, and muscarinic receptors.
- Elimination Pathways: Primarily hepatic metabolism followed by renal and fecal excretion.
Dosage
Standard Dosage
Adults:
- Schizophrenia: Initial dose: 2-5 mg twice daily, gradually increased to 15-20 mg/day. Maximum dose: 40 mg/day.
- Non-psychotic anxiety: 1-2 mg twice daily, not to exceed 6 mg/day. Treatment duration should not exceed 12 weeks.
- Nausea and vomiting: 1-2 mg twice daily up to Max 6 mg/ day
Children (6-12 years):
- Schizophrenia: Initial dose: 1 mg once or twice daily, gradually increased as needed, not to exceed 15 mg/day.
- Children below 6 years of age: Safety and efficacy not established.
Special Cases:
- Elderly Patients: Lower starting doses (half of the adult dose) are recommended due to increased sensitivity to side effects.
- Patients with Renal Impairment: Close monitoring is necessary, and dosage adjustment may be required.
- Patients with Hepatic Dysfunction: Dose reduction is recommended due to impaired metabolism.
- Patients with Comorbid Conditions: Careful consideration and dose adjustments are necessary in patients with cardiovascular disease, diabetes, or other relevant conditions.
Clinical Use Cases
Trifluoperazine is not typically indicated for use in settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations like cardiac arrest or status epilepticus.
Dosage Adjustments:
Dosage adjustments may be necessary based on patient response, tolerability, and the presence of renal or hepatic impairment. Genetic polymorphisms affecting drug metabolism should also be considered.
Side Effects
Common Side Effects:
Drowsiness, dizziness, dry mouth, blurred vision, constipation, insomnia, extrapyramidal symptoms (EPS) like tremors and dystonia, weight gain, and menstrual irregularities.
Rare but Serious Side Effects:
Neuroleptic malignant syndrome (NMS), tardive dyskinesia, agranulocytosis, severe allergic reactions, seizures, and cardiac arrhythmias.
Long-Term Effects:
Tardive dyskinesia (potentially irreversible movement disorder) can occur with prolonged use.
Adverse Drug Reactions (ADR):
NMS, agranulocytosis, and severe allergic reactions require immediate medical attention.
Contraindications
Hypersensitivity to trifluoperazine or other phenothiazines, coma, severe CNS depression, blood dyscrasias, bone marrow depression, severe liver disease, and existing long QT syndrome or a history of Torsade de Pointes.
Drug Interactions
Trifluoperazine interacts with numerous medications. Clinically significant interactions include those with:
- CNS depressants: Additive sedative effects.
- Anticholinergic drugs: Increased anticholinergic side effects.
- Antihypertensives: Enhanced hypotensive effects.
- QT prolonging drugs: Increased risk of arrhythmias.
- CYP450 substrates, inducers, and inhibitors: Altered trifluoperazine metabolism.
- Lithium, guanethidine, phenytoin, warfarin.
- Alcohol and other CNS depressants.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Not established. Use during pregnancy only if the potential benefit outweighs the risk to the fetus, especially during the first trimester. Neonatal effects have been reported after third-trimester exposure.
- Breastfeeding: Trifluoperazine is excreted in breast milk and can have adverse effects on the nursing infant. The decision to breastfeed should be made considering the risks and benefits for both the mother and the infant. Alternative antipsychotic agents with more data supporting their safety during breastfeeding may be preferred.
Drug Profile Summary
- Mechanism of Action: D2 receptor antagonist.
- Side Effects: Drowsiness, dizziness, dry mouth, EPS, tardive dyskinesia, NMS.
- Contraindications: Hypersensitivity, coma, CNS depression, blood dyscrasias, severe liver disease, long QT syndrome.
- Drug Interactions: CNS depressants, anticholinergics, antihypertensives, QT prolonging drugs, CYP450 interacting drugs.
- Pregnancy & Breastfeeding: Use with caution, considering risks and benefits.
- Dosage: See detailed dosage section above.
- Monitoring Parameters: Monitor for EPS, NMS, blood pressure, liver function, and complete blood counts.
Popular Combinations
Trifluoperazine is not commonly used in combination with other antipsychotics. However, adjunctive medications like anticholinergics may be used to manage EPS.
Precautions
- General Precautions: Screen for allergies, underlying medical conditions (especially cardiac, hepatic, and renal), and concomitant medications.
- Specific Populations: See detailed dosage adjustments above.
- Lifestyle Considerations: Avoid alcohol and other CNS depressants. Caution while driving or operating machinery due to potential drowsiness and impaired alertness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Trifluoperazine?
A: See the detailed Dosage section above, as it varies based on indication, age, and patient-specific factors.
Q2: What are the most common side effects of Trifluoperazine?
A: Common side effects include drowsiness, dizziness, dry mouth, blurred vision, constipation, EPS (e.g., tremors, dystonia), weight gain, and menstrual changes.
A: Neuroleptic malignant syndrome (NMS), tardive dyskinesia, agranulocytosis, severe allergic reactions, and cardiac arrhythmias are serious side effects and require immediate medical intervention.
Q4: Can Trifluoperazine be used during pregnancy?
A: Trifluoperazine should be used during pregnancy only if the potential benefit outweighs the risk to the fetus. Discuss the risks and benefits with your patient.
Q5: Can Trifluoperazine be used during breastfeeding?
A: Trifluoperazine is present in breast milk. The decision to breastfeed should be made in consultation with the patient, weighing the risks and benefits for both the mother and the infant. Consider alternative medications.
Q6: What are the contraindications to using Trifluoperazine?
A: Contraindications include hypersensitivity to trifluoperazine or phenothiazines, coma, severe CNS depression, blood dyscrasias, severe liver disease, and long QT syndrome.
Q7: What are the important drug interactions with Trifluoperazine?
A: Trifluoperazine can interact with numerous medications, including CNS depressants, anticholinergics, antihypertensives, and QT-prolonging drugs. Consult drug interaction resources for a comprehensive list.
Q8: How does Trifluoperazine differ from other antipsychotics?
A: Trifluoperazine is a first-generation antipsychotic and tends to have a higher risk of EPS compared to second-generation antipsychotics.
Q9: How should Trifluoperazine be discontinued?
A: Gradual tapering of the dose is recommended to avoid withdrawal symptoms, especially after long-term use.
