Risk of hepatotoxicity-related hospitalizations among patients treated with opioid/acetaminophen combination prescription pain medications

Pain Med. 2010 Nov;11(11):1718-25. doi: 10.1111/j.1526-4637.2010.00979.x.

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.

MeSH terms

  • 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
  • Female
  • Hospitalization / statistics & numerical data*
  • Humans
  • Hydrocodone / administration & dosage
  • Hydrocodone / adverse effects
  • Male
  • Middle Aged
  • Oxycodone / administration & dosage
  • Oxycodone / adverse effects
  • Pain / drug therapy
  • Risk Factors

Substances

  • Analgesics, Opioid
  • Drug Combinations
  • Acetaminophen
  • Hydrocodone
  • Oxycodone