A fixed-dose combination of a typical antipsychotic (phenothiazine derivative) and an anticholinergic agent. Trifluoperazine is a high-potency antipsychotic used for schizophrenia and other psychotic disorders. Trihexyphenidyl is added to counteract the extrapyramidal symptoms (EPS) induced by trifluoperazine, particularly in the initial phase of treatment. This combination is primarily used for the management of psychotic disorders where EPS is a significant concern.
Adult: Initially, 1 tablet (Trifluoperazine 2.5mg + Trihexyphenidyl 1mg) twice daily. May be increased gradually based on response and tolerance. Usual maintenance: 2-4 tablets per day in divided doses. Maximum trifluoperazine dose typically 30-40mg/day; anticholinergic dose should be the minimum effective.
Note: Administer orally with or after food to minimize gastric upset. Tablet can be taken with a full glass of water. Do not crush or chew unless advised. Avoid abrupt discontinuation.
Trifluoperazine exerts its antipsychotic effect primarily by blocking postsynaptic dopamine D2 receptors in the mesolimbic pathway of the brain. It also has moderate antagonistic activity at alpha-1 adrenergic receptors and histamine H1 receptors. Trihexyphenidyl is a competitive antagonist at central muscarinic acetylcholine receptors (M1, M4), reducing the relative cholinergic excess in the striatum caused by dopamine blockade, thereby preventing or treating extrapyramidal symptoms.
Pregnancy: Category C (US FDA). Not recommended unless potential benefit justifies risk. Phenothiazines cross placenta. Risk of EPS, withdrawal, and other effects in neonate. Use only if clearly needed.
Driving: May impair alertness, coordination, and reaction time. Patients should not drive or operate machinery until their individual response is known, especially during initial therapy and dose adjustments.
| Other CNS Depressants (Alcohol, Opioids, Benzodiazepines) | Additive CNS depression, respiratory depression | Major |
| Anticholinergics (Atropine, Antihistamines, TCAs) | Additive anticholinergic toxicity (delirium, hyperthermia, ileus) | Major |
| Levodopa, Dopamine Agonists | Mutual antagonism; reduced efficacy of both | Major |
| QT-prolonging drugs (Class IA/III antiarrhythmics, Macrolides, Fluoroquinolones) | Increased risk of torsades de pointes | Major |
| Enzyme Inducers (Phenobarbitone, Carbamazepine, Rifampicin) | Reduced plasma levels of trifluoperazine | Moderate |
| Enzyme Inhibitors (Fluoxetine, Paroxetine, CYP2D6 inhibitors) | Increased plasma levels of trifluoperazine, risk of toxicity | Moderate |
| Antihypertensives | Potentiated hypotension | Moderate |
| Metoclopramide | Increased risk of EPS | Moderate |
Same composition (Trifluoperazine (2.5mg) + Trihexyphenidyl (1mg)), different brands: