Acetaminophen in chronic liver disease

The safety of acetaminophen in therapeutic doses was evaluated in subjects with stable chronic liver disease. Six subjects with chronic liver disease were given 4.0 gm daily for 5 days. Although the mean half-life (t 1/2) acetaminophen was 3.42 hr, there was no evidence of drug cumulation or hepatotoxicity. A double-blind, two-period crossover design was also used to evaluate acetaminophen in 20 subjects. Acetaminophen, at a dose of 4.0 gm daily for 13 days, was well tolerated by these subjects with stable chronic liver disease. One subject developed symptoms, which worsened and were associated with deterioration in the results of laboratory studies, while taking acetaminophen. Subsequent challenges with 4.0 gm acetaminophen daily for periods of 10 and 14 days were well tolerated, which indicates that the deterioration was not related to the drug. During this study there were no abnormalities indicative of an adverse reaction to acetaminophen. There is, therefore, no contraindication to the use of acetaminophen in therapeutic doses in the presence of stable chronic liver disease.