Clozapine × Tramadol

Tramadol and clozapine both depress the central nervous system, and together they raise the risk of profound sedation, respiratory depression, coma and death (tramadol label). Both lower the seizure threshold: tramadol can cause seizures even at recommended doses and adds to the seizure potential of antipsychotics, while the seizure risk of clozapine rises with the dose (tramadol and clozapine labels). Clozapine slows gut motility through its potent anticholinergic effect and tramadol also reduces motility, so together they increase the risk of severe constipation and bowel obstruction (US clozapine and tramadol labels). The liver enzyme CYP2D6 converts tramadol to its active metabolite. The US clozapine label says clozapine can raise levels of drugs broken down by CYP2D6, while the Spanish clozapine label reports no clinically relevant interactions with such drugs. Clozapine is not on the serotonergic drug lists in the tramadol labels, and no document describes serotonin syndrome for this pair.

Central nervous system depression shows as unusual drowsiness, confusion, pinpoint pupils, slow and shallow breathing, and coma in severe cases (tramadol label). Seizures present as sudden loss of consciousness with convulsions and are more likely at higher doses of either drug. Constipation, abdominal distension or pain, nausea and vomiting point to slowed gut motility that can progress to obstruction (US clozapine label). Both drugs can lower blood pressure, causing dizziness or fainting on standing up (clozapine and tramadol labels).

Under the US tramadol label (FDA), combine tramadol with antipsychotics only when other pain treatment options are inadequate. Use the lowest effective tramadol dose and the shortest duration of combined use (Spanish tramadol label). When adding tramadol for a patient who already takes clozapine, start tramadol at a lower dose than usual and titrate to response (US tramadol and clozapine labels). Keep tramadol at or below 400 mg a day, since the seizure risk rises above that dose (tramadol label). Uncontrolled epilepsy contraindicates both tramadol and clozapine (both labels). If seizures occur, reduce the clozapine dose and start anticonvulsant treatment if needed (clozapine label). Warn the patient and carers about drowsiness and signs of respiratory depression, and advise against driving or operating machinery (clozapine and tramadol labels). Check bowel function often, treat constipation promptly and consider preventive laxatives in high-risk patients (US clozapine label).