Dantrolene sodium and hepatic injury

Abstract

This is a report on hepatic adverse events associated with dantrolene therapy. All cases reported to the manufacturer are included, from all sources, through 1987. Of 122 cases containing sufficient data to analyze, 47 patients had asymptomatic transaminase elevations, 12 had additional mild (≤12.5 mg/dl) hyperbilirubinemia, 36 had jaundice, and 27 patients died. There is an overrepresentation of women over 35 years and patients with multiple sclerosis in the fatal group compared with the study population as a whole (not statistically significant). Mean dantrolene dose was 582 mg/d in fatal cases and 263 mg/d in the nonfatal group. Generally, at least 2 months of therapy was given before injury occurred. Concomitant drugs and nonhepatic, drug-independent disease were associated with a fatal outcome. Serum bilirubin may be predictive for death (mean of 17.0 mg/dl in the fatal group compared with 6.5 mg/dl in nonfatal cases). Of available biopsy reports, 68% included chronic active hepatitis or precirrhotic/cirrhotic lesions. Physicians should monitor liver function in patients taking dantrolene.