Protease inhibitor-induced carbamazepine toxicity

Neurologic manifestations of HIV infection are quite diverse and can develo p into seizures. Because new drug therapies have been developed, it is impo rtant to know the interactions between antiretroviral and antiepileptic age nts. A 36-year-old patient with HIV developed a set of progressive left hem iparesis and secondarily generalized partial seizures related to progressiv e multifocal leukoencephalopathy. Phenytoin and carbamazepine were necessar y to control the seizures. Instead of diverse antiretroviral therapies, the viral load was increased. Protease inhibitors (ritonavir and saquinavir) w ere added to the treatment and the patient developed progressive ataxia rel ated to carbamazepine toxicity. Carbamazepine was discontinued and the pati ent remained asymptomatic. The patient was diagnosed with carbamazepine tox icity related to the introduction of ritonavir. Ritonavir is a potent inhib itor of hepatic cytochrome P450, mainly the CYP3A4 isoform. Carbamazepine i s metabolized by this subsystem. Ritonavir acted as a CYP3A4 inhibitor, dim inishing carbamazepine metabolism and provoking an increase in serum levels and clinical toxicity. We present a case of interaction between ritonavir and carbamazepine. Interaction between antiepileptic and antiretroviral age nts is an emergent problem caused by the increasing association of the two therapies. We recommend strict monitoring of serum antiepileptic drug (AED) levels to avoid toxicity and inadequate seizure control.