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

• Published in: Pain medicine (Malden, Mass.) Vol. 11; no. 11; pp. 1718 - 1725
• Main Authors: Duh, Mei Sheng, Vekeman, Francis, Korves, Caroline, Lefebvre, Patrick, Dial, Ellison, Latremouille-Viau, Dominick, Wei, Robert S., Stangle, Bruce E., Lafeuille, Marie-Helene, Michna, Edward, Greenberg, Paul E.
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01.11.2010
• Subjects: Acetaminophen; Acetaminophen - administration & dosage; Acetaminophen - adverse effects; Adult; Aged; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - adverse effects; Chemical and Drug Induced Liver Injury - epidemiology; Chemical and Drug Induced Liver Injury - etiology; Drug Combinations; Drugs; Female; hepatotoxicity; Hospitalization - statistics & numerical data; Humans; Hydrocodone; Hydrocodone - administration & dosage; Hydrocodone - adverse effects; Male; Middle Aged; Opioids; Oxycodone; Oxycodone - administration & dosage; Oxycodone - adverse effects; Pain; Pain - drug therapy; Pain Management; Risk Factors; Safety
• ISSN: 1526-2375; 1526-4637
• DOI: 10.1111/j.1526-4637.2010.00979.x

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.