Effect of maximal therapeutic acetaminophen (APAP) dosing in alcoholics

Background APAP, at the maximal recommended daily dose (4 g/day), is considered safe for most patients, regardless of co‐morbid conditions. Some practitioners advise alcoholics to avoid APAP or to decrease the daily dose. This recommendation is not supported by prospective data. Studies of shorter duration suggest that 4 gram/day APAP is safe for alcoholics. This study evaluated the hepatic effects of 4 g/day APAP dosing for 3 days in alcoholics. Methods A prospective, double‐blinded, randomized, placebo‐controlled trial of alcoholics was conducted at 2 detoxification centers. Exclusion criteria included AST or ALT >200 IU/L or INR >1.5. Randomization was 2:1 APAP (1g every 4‐hrs for 4 doses) or placebo for 3 days. Serum APAP, AST, ALT, and INR were measured at baseline, day 3, and day 5. Results 385 patients completed the trial (262 APAP, 123 placebo). Treatment groups were not different in demographics, severity of alcoholism or nutritional status. There was no difference in AST, ALT or INR group means on any day; the study had 95% probability of detecting a 15 IU/L mean difference in AST. 11 patients (7 APAP, 4 placebo; p=0.75) developed an AST greater than 200 IU/L (range 203 ‐ 448 IU/L). Conclusions AST and ALT abnormalities and fluctuations are common in alcoholics in detoxification. Alcoholics treated with the maximal daily recommended dose of APAP for 3 days did not develop liver injury. Clinical Pharmacology & Therapeutics (2005) 77 , P94–P94; doi: 10.1016/j.clpt.2004.12.251