Protease inhibitor-induced carbamazepine toxicity.
Neurologic manifestations of HIV infection are quite diverse and can develop into seizures. Because new drug therapies have been developed, it is important to know the interactions between antiretroviral and antiepileptic agents. A 36-year-old patient with HIV developed a set of progressive left hemiparesis and secondarily generalized partial seizures related to progressive multifocal leukoencephalopathy. Phenytoin and carbamazepine were necessary to control the seizures. Instead of diverse antiretroviral therapies, the viral load was increased. Protease inhibitors (ritonavir and saquinavir) were added to the treatment and the patient developed progressive ataxia related to carbamazepine toxicity. Carbamazepine was discontinued and the patient remained asymptomatic. The patient was diagnosed with carbamazepine toxicity related to the introduction of ritonavir. Ritonavir is a potent inhibitor of hepatic cytochrome P450, mainly the CYP3A4 isoform. Carbamazepine is metabolized by this subsystem. Ritonavir acted as a CYP3A4 inhibitor, diminishing 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 agents 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.
Berbel Garcia
A
A
Department of Neurology, Hospital 12 de Octubre, Madrid, Spain.
Latorre Ibarra
A
A
Porta Etessam
J
J
Martinez Salio
A
A
Perez Martinez
D
D
Siaz Diaz
R
R
Toledo Heras
M
M
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002220:Carbamazepine / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D004828:Epilepsies, Partial / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010291:Paresis / Q000188:drug therapy; D019438:Ritonavir / Q000009:adverse effects* / Q000493:pharmacokinetics; D013997:Time Factors
D000927:Anticonvulsants; D017320:HIV Protease Inhibitors; D002220:Carbamazepine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D019438:Ritonavir