Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Clin Pharmacol Ther. 2021 Oct;110(4):1011-1017. doi: 10.1002/cpt.2314. Epub 2021 Jun 27.
Polypharmacy is common among patients taking prescription opioids long-term, and the codispensing of interacting medications may further increase opioid overdose risk. To identify nonopioid medications that may increase opioid overdose risk in this population, we conducted a case-crossover-based screening of electronic claims data from IBM MarketScan and Optum Clinformatics Data Mart spanning 2003 through 2019. Eligible patients were 18 years of age or older and had at least 180 days of continuous enrollment and 90 days of prescription opioid use immediately before an opioid overdose resulting in an emergency room visit or hospitalization. The main analysis quantified the odds ratio (OR) between opioid overdose and each nonopioid medication dispensed in the 90 days immediately before the opioid overdose date after adjustment for prescription opioid dosage and benzodiazepine codispensing. Additional analyses restricted to patients without cancer diagnoses and individuals who used only oxycodone for 90 days immediately before the opioid overdose date. The false discovery rate (FDR) was used to account for multiple testing. We identified 24,866 individuals who experienced opioid overdose. Baclofen (OR 1.56; FDR < 0.01; 95% confidence interval (CI), 1.29 to 1.89), lorazepam (OR 1.53; FDR < 0.01; 95% CI, 1.25 to 1.88), and gabapentin (OR 1.16; FDR = 0.09; 95% CI, 1.04 to 1.28), among other nonopioid medications, were associated with opioid overdose. Similar patterns were observed in noncancer patients and individuals who used only oxycodone. Interventions may focus on prescribing safer alternatives when a potential for interaction exists.
长期服用处方类阿片的患者普遍存在多种药物治疗的情况，而同时开具相互作用的药物可能会进一步增加阿片类药物过量的风险。为了确定在该人群中可能增加阿片类药物过量风险的非阿片类药物，我们对 IBM MarketScan 和 Optum Clinformatics Data Mart 中的电子索赔数据进行了基于病例交叉的筛选，时间范围为 2003 年至 2019 年。符合条件的患者年龄在 18 岁或以上，至少有 180 天的连续入组和 90 天的处方类阿片药物使用，紧接着发生了阿片类药物过量导致急诊室就诊或住院的情况。主要分析在调整处方类阿片药物剂量和苯二氮䓬类药物同时开具的情况下，计算了在阿片类药物过量日期前 90 天内开出的每种非阿片类药物与阿片类药物过量之间的比值比 (OR)。额外的分析仅限于没有癌症诊断的患者和在阿片类药物过量日期前的 90 天内仅使用羟考酮的个体。错误发现率 (FDR) 用于考虑多次检验。我们确定了 24866 名经历阿片类药物过量的个体。巴氯芬 (OR 1.56；FDR<0.01；95%置信区间 (CI)，1.29 至 1.89)、劳拉西泮 (OR 1.53；FDR<0.01；95% CI，1.25 至 1.88) 和加巴喷丁 (OR 1.16；FDR=0.09；95% CI，1.04 至 1.28) 等非阿片类药物与阿片类药物过量有关。在非癌症患者和仅使用羟考酮的个体中也观察到类似的模式。当存在相互作用的潜在风险时，干预措施可能侧重于开具更安全的替代药物。
