Potential interaction between carbamazepine and loxapine: case report and retrospective review

OBJECTIVE: To report a potential interaction between carbamazepine (CBZ), an anticonvulsant medication, and loxapine, an antipsychotic. CBZ is being increasingly used to treat a variety of psychiatric disorders. Because of this, the potential for multiple-drug therapy and subsequent drug interactions is increased. METHODS: We prospectively monitored plasma CBZ and carbamazepine epoxide (CBZE) concentrations in a single patient during and after withdrawal of loxapine comedication. Additionally, we retrospectively evaluated four patients who had received concomitant therapy with CBZ and loxapine. RESULTS: Plasma CBZE/CBZ ratios decreased from 0.76 to 0.18 following discontinuation of loxapine. Absolute CBZE plasma concentrations also decreased from 1.7 to 0.6 micrograms/mL after loxapine therapy was stopped. Retrospectively screened patients who were receiving concomitant loxapine-CBZ therapy all had unusually elevated CBZE/CBZ plasma concentration ratios (0.75-1.91). CONCLUSIONS: These cases suggest that an interaction occurs between loxapine and CBZ. Possible mechanisms include either induction of CBZ metabolism to its epoxide metabolite, or inhibition of the enzymatic metabolism of CBZE (epoxide hydrolase).