fluconazole and carbamazepine

Fluconazole inhibits the hepatic cytochrome P450 enzyme CYP3A4, which is the primary pathway for carbamazepine metabolism. This inhibition reduces carbamazepine clearance, increasing its plasma concentrations and those of its active metabolite (carbamazepine-10,11-epoxide).

Raised carbamazepine concentrations can cause dose-related toxicity, including dizziness, ataxia, diplopia, nystagmus, and confusion. Severe toxicity may lead to seizures or cardiac arrhythmias. The risk is greatest in patients on stable carbamazepine therapy who start fluconazole.

If co-prescription is necessary, monitor plasma carbamazepine concentrations and clinical signs of toxicity, especially at the start of fluconazole therapy. Reduce the carbamazepine dose as required. Advise patients to report neurological symptoms.

Well documented in clinical studies and case reports. The interaction is predictable and clinically significant.