Analysis of data from special drug use surveillance on elevation of liver function tests in Japanese patients administered high dose acetaminophen

Abstract

Background: Acetaminophen is widely used for pain relief, but is known to cause liver injury in cases of overdose. Previously, the maximum dose in Japan was 1500 mg/day, which was much lowerthan those in othercountries. In 2011, the approved maximum dose was changed to 4000 mg/day in Japan, raising concerns over the safety of its use in Japanese patients. Therefore, we performed an epidemiological study to examine the safety of acetaminophen. In this study, we analyzed the data from a special drug use surveillance on elevation of liver function tests in Japanese patients, to assess drug-induced liver injury (Dili) of high-dose acetaminophen. Methods: Patients who were treated with a high dose (2400 to 4000 mg/day) of acetaminophen for 4 to 24 weeks were included. Data were collected from the hospital medical information systems of 87 hospitals, from which consecutive eligible patients between January 2011 and April 2013 were identified. An abnormal liver function test (LFT) was defined as elevated alanine transaminase (ALT) level greaterthan 3 times the upperlimit of the normal range. The prevalence of abnormal LFT was calculated, and correlation with background factors was analyzed using logistic regression. Results: A total of 703 cases that met the inclusion criteria were analyzed. Abnormal LFT findings were observed in 22 cases (3.1%), and causality with acetaminophen could not be ruled out in 7 cases (1.0%). A logistic regression analysis showed that abnormal LFT findings correlated significantly with the presence of concomitant disease, a history of allergic disease, the duration of treatment, and on-demand use. Conclusion: The prevalence of elevated ALT level among Japanese patients treated with acetaminophen was almost identical to that reported in other countries. However, a significant relationship between abnormal LFT and some clinical factors including the duration of treatment was found. However, this study had a limitation of inadequate patient population, suggesting a need to collect data continuously in Japan.