title: A case of a potential drug interaction between clobazam and etravirine-based antiretroviral therapy.
abstract: The cytochrome P450 isoforms primarily involved in clobazam metabolism are CYP3A4 and 2C19. Drugs that modulate these enzymes would then be expected to alter the exposure of clobazam and its major metabolites. Etravirine, a second-generation non-nucleoside reverse transcriptase inhibitor has been shown to induce CYP3A4, while inhibiting CYP2C9 and CYP2C19. We report a case in which a potential drug interaction between clobazam and etravirine may have led to increased concentrations of clobazam and its pharmacologically active metabolite, N-desmethylclobazam, causing neurotoxic symptoms.
authors.affiliation: Department of Infectious Diseases & HIV, St Michael's Hospital, Toronto, ON, Canada. naccaratom@smh.ca
authors.forename: Mark
authors.initials: M
authors.lastname: Naccarato
authors.forename: Deborah
authors.initials: D
authors.lastname: Yoong
authors.forename: Colin
authors.initials: C
authors.lastname: Kovacs
authors.forename: Kevin
authors.initials: K
authors.lastname: Gough
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors; D001569:Benzodiazepines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000078306:Clobazam; D065729:Cytochrome P-450 CYP2C9; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D020258:Neurotoxicity Syndromes / Q000209:etiology; D009570:Nitriles; D011724:Pyridazines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; C451734:etravirine; D001569:Benzodiazepines; D000078306:Clobazam; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases