Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, University of Florida College of Pharmacy, Gainesville, Florida, USA.
Division of Outcomes and Translational Sciences, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA.
Clin Pharmacol Ther. 2024 Oct;116(4):1005-1012. doi: 10.1002/cpt.3314. Epub 2024 May 26.
Hydrocodone, tramadol, codeine, and oxycodone are commonly prescribed opioids that rely on activation by cytochrome P450 2D6 (CYP2D6). CYP2D6 inhibitors can significantly decrease CYP2D6 activity, leading to reduced generation of active metabolites, and impairing pain control. To understand this impact, we assessed emergency department (ED) visits in patients initiating these CYP2D6-dependent opioids while on CYP2D6-inhibitor antidepressants vs. antidepressants that do not inhibit CYP2D6. This retrospective cohort study included adult patients prescribed CYP2D6-dependent opioids utilizing electronic health records data from the University of Florida Health (2015-2021). The association between ED visits and inhibitor exposure was tested using multivariable logistic regression. The primary analysis had 12,118 patients (72% female; mean (SD) age, 55 (13.4)) in the hydrocodone/tramadol/codeine cohort and 5,547 patients (64% female; mean (SD) age, 53.6 (14.2)) in the oxycodone cohort. Hydrocodone/tramadol/codeine-treated patients exposed to CYP2D6-inhibitor antidepressants (n = 7,043) had a higher crude rate of pain-related ED visits than those taking other antidepressants (n = 5,075) (3.28% vs. 1.87%), with an adjusted odds ratio (aOR) of 1.75 (95% CI: 1.36 to 2.24). Similarly, in the oxycodone cohort, CYP2D6-inhibitor antidepressant-exposed individuals (n = 3,206) had a higher crude rate of ED visits than individuals exposed to other antidepressants (n = 2,341) (5.02% vs. 3.37%), with aOR of 1.70 (95% CI: 1.27-2.27). Similar findings were observed in secondary and sensitivity analyses. Our findings suggest patients with concomitant use of hydrocodone/tramadol/codeine or oxycodone and CYP2D6 inhibitors have more frequent ED visits for pain, which may be due to inadequate pain control.
氢可酮、曲马多、可待因和羟考酮是常用的依赖细胞色素 P450 2D6（CYP2D6）激活的阿片类药物。CYP2D6 抑制剂可显著降低 CYP2D6 活性，导致活性代谢物生成减少，并损害疼痛控制。为了了解这种影响，我们评估了在开始使用 CYP2D6 依赖性阿片类药物时同时使用 CYP2D6 抑制剂抗抑郁药与不抑制 CYP2D6 的抗抑郁药的患者在急诊就诊的情况。这项回顾性队列研究纳入了利用佛罗里达大学健康电子健康记录数据（2015-2021 年）处方 CYP2D6 依赖性阿片类药物的成年患者。使用多变量逻辑回归检验 ED 就诊与抑制剂暴露之间的关联。主要分析包括氢可酮/曲马多/可待因队列中的 12118 例患者（72%为女性；平均[标准差]年龄，55[13.4]）和羟考酮队列中的 5547 例患者（64%为女性；平均[标准差]年龄，53.6[14.2]）。暴露于 CYP2D6 抑制剂抗抑郁药的氢可酮/曲马多/可待因治疗患者（n=7043）的疼痛相关 ED 就诊的粗率高于服用其他抗抑郁药的患者（n=5075）（3.28% vs. 1.87%），调整后的比值比（aOR）为 1.75（95%CI：1.36 至 2.24）。同样，在羟考酮队列中，暴露于 CYP2D6 抑制剂抗抑郁药的个体（n=3206）的 ED 就诊粗率高于暴露于其他抗抑郁药的个体（n=2341）（5.02% vs. 3.37%），aOR 为 1.70（95%CI：1.27 至 2.27）。在二次和敏感性分析中也观察到了类似的结果。我们的研究结果表明，同时使用氢可酮/曲马多/可待因或羟考酮和 CYP2D6 抑制剂的患者因疼痛而更频繁地去急诊就诊，这可能是由于疼痛控制不足所致。
