Anticonvulsant and Antiretroviral Interactions

Abstract

OBJECTIVE To evaluate the clinical significance of interactions between anticonvulsant and antiretroviral agents and provide recommendations regarding their concurrent use. DATA SOURCES A PubMed search (1966 to April 2003) was conducted using individual anticonvulsant and antiretroviral drug names and the following key search terms: anticonvulsant, antiepileptic, antiretroviral, protease inhibitor, and pharmacokinetic. Abstracts from scientific meetings that pertained to drug interactions were manually reviewed. STUDY SELECTION AND DATA EXTRACTION All articles identified by the PubMed search were examined. Articles and abstracts from scientific meetings with relevant information were included. DATA SYNTHESIS Six case reports were identified that describe interactions between anticonvulsant agents and protease inhibitors. In several reports, carbamazepine serum concentrations increased by approximately two- to threefold with concurrent ritonavir, resulting in carbamazepine-related toxicity. Carbamazepine was also associated with loss of viral suppression when combined with indinavir. Phenytoin serum concentrations were decreased with nelfinavir in a patient who developed recurrent seizures. The effect of ritonavir on phenytoin was variable; a 30% reduction in phenytoin serum concentration occurred in one patient, while no apparent change was observed in another. Interactions with nonnucleoside reverse-transcriptase inhibitors are poorly characterized because existing data involve concurrent protease inhibitor therapy. The utility of newer anticonvulsant agents is explored. Experience with newer anticonvulsant agents in 2 patients at our site is also described. CONCLUSION Limited data exist regarding interactions between anticonvulsant and antiretroviral agents. Valproic acid and newer anticonvulsant agents may provide useful alternatives to first-generation agents. Clinicians need to be diligent when monitoring for anticonvulsant–antiretroviral interactions because of the potential for toxicity, loss of seizure control, and incomplete viral suppression.