A fixed-dose combination (FDC) of a benzodiazepine (Chlordiazepoxide) and a typical antipsychotic of the phenothiazine class (Trifluoperazine). Primarily used for the management of moderate to severe anxiety, tension, and agitation, especially when associated with psychoneurotic states or somatic conditions. The combination leverages the anxiolytic and sedative effects of Chlordiazepoxide with the antipsychotic and antiemetic properties of Trifluoperazine, offering a synergistic effect for specific clinical presentations. Its use is now more restricted due to the risk of significant sedation, extrapyramidal symptoms (EPS), and dependence.
Adult: Usually 1 tablet (Chlordiazepoxide 10mg + Trifluoperazine 1mg) two to three times daily. The dose must be individualized. Start low (e.g., half tablet twice daily) and titrate based on response and tolerability.
Note: Administer orally with or without food. To minimize gastric upset, can be taken with food. Tablets should be swallowed whole with a glass of water. Avoid abrupt discontinuation after prolonged use.
The combination exerts a dual action on the central nervous system. Chlordiazepoxide potentiates GABAergic inhibition by binding to a specific site on the GABA-A receptor, increasing chloride ion influx, leading to neuronal hyperpolarization and CNS depression. Trifluoperazine acts primarily as a postsynaptic dopamine D2 receptor antagonist in the mesolimbic and mesocortical pathways. It also has significant antagonistic effects at alpha-1 adrenergic, histamine H1, and muscarinic cholinergic receptors.
Pregnancy: Category D (US FDA). Both drugs cross the placenta. Chlordiazepoxide use in first trimester may be associated with increased risk of congenital malformations. Use in late pregnancy can cause neonatal flaccidity, withdrawal symptoms, and respiratory depression. Should be avoided, especially in first and third trimesters. Use only if potential benefit justifies clear risk.
Driving: STRONGLY ADVISED AGAINST. Causes drowsiness, dizziness, and blurred vision, impairing the ability to drive or operate machinery. Effects may persist into the next day.
| Alcohol, Opioids, Barbiturates, other CNS Depressants | Additive CNS depression, profound sedation, respiratory depression, risk of death | Major |
| Levodopa, Dopamine Agonists | Trifluoperazine antagonizes dopamine, reducing efficacy of Parkinson's drugs | Major |
| Anticholinergics (e.g., Trihexyphenidyl, Atropine) | Additive anticholinergic side effects (dry mouth, constipation, urinary retention, confusion) | Moderate |
| Antihypertensives | Enhanced hypotensive effect, especially postural hypotension | Moderate |
| Enzyme Inducers (e.g., Phenytoin, Carbamazepine, Rifampicin) | Increased metabolism of both drugs, reducing their efficacy | Moderate |
| Enzyme Inhibitors (e.g., Fluoxetine, Paroxetine, Cimetidine, Ketoconazole) | Increased plasma levels of chlordiazepoxide/trifluoperazine, leading to toxicity | Moderate |
| Drugs prolonging QT interval (e.g., Erythromycin, Class IA/III antiarrhythmics) | Increased risk of life-threatening cardiac arrhythmias (Torsades de Pointes) | Major |
| Lithium | Increased risk of neurotoxicity (encephalopathy) and EPS | Moderate |
Same composition (Chlordiazepoxide (10mg) + Trifluoperazine (1mg)), different brands: