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药物相互作用对老年男性口服羟考酮不良反应的影响。

The impact of drug interactions on adverse effects of oral oxycodone in male geriatric patients.

机构信息

College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.

College of Pharmacy & Institute of Pharmaceutical Science and Technology, Ajou University, Suwon-si, Korea.

出版信息

J Clin Pharm Ther. 2020 Oct;45(5):976-982. doi: 10.1111/jcpt.13113. Epub 2020 Feb 18.

Abstract

WHAT IS KNOWN AND OBJECTIVE

With increased opioid use, drug-drug interactions (DDIs) and associated adverse events are growing among geriatric patients. However, the clinical significance of potential metabolic DDIs associated with opioid use has not been fully evaluated among geriatric patients. Particularly, cytochrome (CYP) P450 enzymes are important in drug metabolism of oxycodone and a black box warning for oxycodone reveals serious risks associated with drug-oxycodone interactions. This study focused on the use of oxycodone in geriatric patients to evaluate its adverse drug reactions (ADRs) and DDIs associated with CYP P450 enzymes.

METHODS

A retrospective cohort study using patients treated at Korea Veterans Hospital was performed. Data from male patients aged 65 years and older who received oxycodone were analysed. Binomial variables describing patient-related characteristics, drug-related characteristics and CYP-mediating drugs were constructed. Associations between these variables and the frequency of ADRs were determined. The odds ratio (OR) and adjusted odds ratio (AOR) were calculated from univariable and multivariable analyses, respectively.

RESULTS AND DISCUSSION

Among 111 patients, 32.4% experienced at least one ADR. The most common ADR was gastrointestinal-related (n = 21), followed by dizziness and drowsiness (n = 8). Use of either CYP2D6 inhibitors or CYP3A4 inhibitors increased the rate of ADRs by 20.4 and 25.4 times, respectively. In the case of patients taking both inhibitors, the adjusted OR was 48.6, and the attributable risk was 97.9%.

WHAT IS NEW AND CONCLUSION

This study suggests that inappropriate combinations of oxycodone with CYP2D6 inhibitors and/or CYP3A4 inhibitors may warrant treatment modification to avoid ADRs in geriatric patients. Clinicians should monitor any signs of ADRs that may reflect DDIs while a geriatric patient is taking oxycodone.

摘要

已知和目的

随着阿片类药物使用的增加,老年患者的药物-药物相互作用(DDI)和相关不良事件也在增加。然而,阿片类药物使用相关的潜在代谢性 DDI 的临床意义尚未在老年患者中得到充分评估。特别是细胞色素(CYP)P450 酶在羟考酮的药物代谢中很重要,羟考酮的黑框警告揭示了与药物-羟考酮相互作用相关的严重风险。本研究重点关注老年患者中羟考酮的使用,以评估与 CYP P450 酶相关的其不良药物反应(ADR)和 DDI。

方法

使用韩国退伍军人医院治疗的患者进行回顾性队列研究。分析了年龄在 65 岁及以上接受羟考酮治疗的男性患者的数据。构建了描述患者相关特征、药物相关特征和 CYP 介导药物的二项变量。确定了这些变量与 ADR 频率之间的关联。使用单变量和多变量分析分别计算比值比(OR)和调整比值比(AOR)。

结果和讨论

在 111 名患者中,32.4%至少发生了一次 ADR。最常见的 ADR 是胃肠道相关(n=21),其次是头晕和嗜睡(n=8)。CYP2D6 抑制剂或 CYP3A4 抑制剂的使用分别使 ADR 发生率增加了 20.4 倍和 25.4 倍。在同时使用两种抑制剂的患者中,调整后的 OR 为 48.6,归因风险为 97.9%。

新内容和结论

本研究表明,羟考酮与 CYP2D6 抑制剂和/或 CYP3A4 抑制剂的不适当组合可能需要调整治疗方案,以避免老年患者发生 ADR。当老年患者服用羟考酮时,临床医生应监测任何可能反映 DDI 的 ADR 迹象。

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