HEPATOTOXICITY ASSOCIATED WITH ACETAMINOPHEN USAGE IN PATIENTS RECEIVING MULTIPLE-DRUG THERAPY FOR TUBERCULOSIS

We report three patients who experienced hepatotoxic reactions in asso ciation with acetaminophen ingestion while undergoing treatment for ac tive tuberculosis with isoniazid, rifampin, and other agents. Ah were young adult women. One patient intentionally took a large amount of ac etaminophen and had typical signs and symptoms of acetaminophen overdo sage; another took acetaminophen in combination form for a minor upper respiratory illness. She experienced no symptoms. The remaining patie nt took acetaminophen to ameliorate the symptoms of fever and malaise that were subsequently attributed to tuberculosis. She had the rapid o nset of signs and symptoms of isoniazid hepatotoxicity. The patterns o f liver function abnormalities were similar: each patient experienced pronounced serum elevations of hepatocellular enzymes with at most onl y modest rises in those of bilirubin. Ah antituberculous drugs were wi thheld until symptoms resolved and laboratory values became normal; th en treatment for tuberculosis was resumed without isoniazid and was su ccessfully completed in all three patients. These cases plus similar r eports in the literature suggest that isoniazid or rifampin, or both, may potentiate the hepatotoxicity of acetaminophen, perhaps by inducti on of cytochrome P450 isozymes that oxidize acetaminophen to its toxic metabolites.