Drug Interactions between Epitol and nelfinavir

GENERALLY AVOID: Coadministration of nelfinavir and carbamazepine may result in decreased plasma concentrations of nelfinavir and increased plasma concentrations of carbamazepine. The proposed mechanism involves carbamazepine induction of nelfinavir metabolism via CYP450 3A4 and, conversely, nelfinavir inhibition of carbamazepine metabolism via the same enzymatic pathway. No data are available from pharmacokinetic studies. In one case report, a 50-year-old HIV-positive male who had been stabilized on carbamazepine 400 mg three times a day developed excessive drowsiness and became unsteady on his feet three days after starting nelfinavir 1250 mg twice daily as part of a new antiretroviral regimen, along with lamivudine and tenofovir. His serum carbamazepine level was 15 mg/L, which was a 53% increase from three weeks prior when it was 9.8 mg/L. Symptoms resolved within 24 hours after the carbamazepine dosage was reduced to 400 mg twice daily, and carbamazepine level was at 9.3 mg/L two days later.

MANAGEMENT: Given the lack of pharmacokinetic data and the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, it may be preferable to avoid using nelfinavir in combination with carbamazepine. Caution is advised if concomitant use is required. In patients already receiving nelfinavir as part of their HIV treatment regimen, close clinical and laboratory monitoring of antiretroviral response is recommended following the addition or discontinuation of carbamazepine. Likewise, if nelfinavir is added to stable carbamazepine therapy, serum drug levels and pharmacologic effects should be closely monitored and the carbamazepine dosage adjusted accordingly. Patients should be advised to contact their doctor if they develop signs of carbamazepine toxicity such as ataxia, disorientation, dizziness, nausea, vomiting, and visual disturbances.

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