ISONIAZID-RIFAMPIN FULMINANT HEPATITIS - POSSIBLE CONSEQUENCE OF ENHANCEMENT OF ISONIAZID HEPATOTOXICITY BY ENZYME-INDUCTION

Abstract

Six cases of fulminant hepatitis in patients treated with isoniazid and rifampin [anti-tuberculosis drugs] are reported. In 4 of these patients, treatment was started within 3 days after general anesthesia. The course of the disease was remarkably similar in all 6 patients: the time interval from the beginning of the isoniazid-rifampin administration to the onset of jaundice was 6-10 days; disorders of consciousness appeared less than 3 days after the onset of jaundice; serum transaminases were 26-80 times the upper limit of normal; the main liver lesion was centrilobular necrosis; hypersensitivity manifestations were absent; all 6 patients recovered. Fulminant hepatitis might be attributable to a hepatotoxic metabolite of isoniazid, the production of which would be increased as a consequence of the enzyme-inducing effect of rifampin and, possibly, other drugs administered for general anesthesia.