Analysis Group, Inc., Boston, Massachusetts 02199, USA.
Pain Med. 2010 Nov;11(11):1718-25. doi: 10.1111/j.1526-4637.2010.00979.x.
This study determined the risk of serious hepatotoxicity resulting in hospitalizations among patients prescribed opioid/acetaminophen combinations.
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.
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).
There is no population data-based evidence supporting elevated risk of hepatotoxicity-related hospitalization associated with opioid/acetaminophen combinations.
本研究旨在确定处方阿片类药物/对乙酰氨基酚复方制剂的患者发生严重肝毒性导致住院的风险。
采用保险索赔数据库进行回顾性队列研究。纳入至少有 1 次羟考酮/对乙酰氨基酚或氢可酮/对乙酰氨基酚复方制剂用药索赔的成年患者（N=1228356）。采用前后设计比较阿片类药物/对乙酰氨基酚复方制剂起始前后严重肝毒性风险。还比较了阿片类药物/对乙酰氨基酚组与阿片类药物单一用药者（N=11809）的对照组之间的严重肝毒性风险。在阿片类药物/对乙酰氨基酚组中，使用二项分布的正态近似法比较了阿片类药物/对乙酰氨基酚治疗前后肝毒性相关住院的风险。使用多变量泊松回归调整组间基线差异，比较了阿片类药物/对乙酰氨基酚组与阿片类药物单一用药组的肝毒性相关住院发生率。
在阿片类药物/对乙酰氨基酚队列中，阿片类药物/对乙酰氨基酚治疗后 6 个月的肝毒性相关住院风险低于治疗前，风险降低了 1.2/10000（治疗前为 0.12%；95%置信区间[CI]，0.12 至 0.13；治疗后为 0.11%；95%CI，0.11 至 0.12）。在 12 个月期间，治疗后 12 个月的风险增加了 2.4/10000（治疗前为 0.14%；95%CI，0.14 至 0.15；治疗后为 0.17%；95%CI，0.16 至 0.18）。调整混杂因素后，阿片类药物单一用药组的肝毒性相关住院率并不低于阿片类药物/对乙酰氨基酚组（阿片类药物单一用药相对于阿片类药物/对乙酰氨基酚的发生率比为 2.9；95%CI，1.8 至 4.7）。
没有基于人群数据的证据支持阿片类药物/对乙酰氨基酚复方制剂与肝毒性相关住院风险升高相关。
