Phenytoin as a possible cause of acetaminophen hepatotoxicity: Case report and review of the literature

A 55-year-old woman was hospitalized for treatment of community-acquired pneumonia. Unexplained, moderate elevations in hepatic transaminase and enzyme levels prompted review of her drug regimen. She had taken acetaminophen 1300-6200 mg/day during the hospitalization. She also received phenytoin for posttraumatic seizures. Acetaminophen was discontinued, and the patient's liver chemistries returned to normal within 2 weeks of discharge. Acetaminophen is metabolized in part by cytochrome P450 (CYP) 2E1, and inducers of CYP2E1 are known to predispose patients to acetaminophen-related hepatotoxicity. Phenytoin induces CYP2C and CYP3A4 isoforms, but not CYP2E1. The literature suggests, however, that CYP3A4 may participate in acetaminophen metabolism to a greater extent than previously realized, and induction of this isoform may predispose patients to acetaminophen-induced hepatotoxicity.