Risk of Hepatotoxicity-Related Hospitalizations among Patients Treated with Opioid/Acetaminophen Combination Prescription Pain Medications

Abstract

Objective. This study determined the risk of serious hepatotoxicity resulting in hospitalizations among patients prescribed opioid/acetaminophen combinations.Methods. A retrospective cohort study using an insurance claims database was conducted. Adult patients with ≥1 claim for oxycodone/acetaminophen or hydrocodone/acetaminophen combinations were included (N=1,228,356). A pre-post design was employed to compare serious hepatotoxicity risk before versus after initiation of opioid/acetaminophen combination. Serious hepatotoxicity risk between the opioid/acetaminophen group and a control group of opioid-alone users (N=11,809) was also examined. Within the opioid/acetaminophen group, risk of hepatotoxicity-related hospitalizations pre- versus post-opioid/acetaminophen treatment was compared using the normal approximation with the binomial distribution. The incidence rate of hepatotoxicity-related hospitalizations for the opioid/acetaminophen group was compared with the opioid-alone group using multivariate Poisson regression adjusting for baseline differences between groups.Results. Of the opioid/acetaminophen cohort, hepatotoxicity-related hospitalization risk in the 6-month post-opioid/acetaminophen period was lower than that in the pre-period with a risk reduction of 1.2 per 10,000 (pre-period=0.12%; 95% confidence interval [CI], 0.12 to 0.13; post-period=0.11%; 95% CI, 0.11 to 0.12). In the 12-month period, risk increased in the post-period by 2.4 per 10,000 (pre-period=0.14%; 95% CI, 0.14 to 0.15; post-period=0.17%; 95% CI, 0.16 to 0.18). After adjusting for confounders, the opioid-alone group did not demonstrate a lower rate of hepatotoxicity-related hospitalizations than the opioid/acetaminophen group (incidence rate ratio of opioid-alone over opioid/acetaminophen=2.9; 95% CI, 1.8 to 4.7).Conclusions. There is no population data-based evidence supporting elevated risk of hepatotoxicity-related hospitalization associated with opioid/acetaminophen combinations. © 2010 Wiley Periodicals, Inc.