Department of Development and Education of Clinical Research; These authors contributed equally to this work; Hiroshi Kato,1-98 Dengakugakubo, Kutsukake-cho 470-1192, Toyoake, Aichi, Japan.
Department of Pharmacotherapeutics and Informatics, Fujita Health University School of Medicine, Aichi, Japan.
Pharmazie. 2024 Aug 1;79(7):169-172. doi: 10.1691/ph.2024.4528.
Gabapentinoid anticonvulsants are standard treatment for neuropathic pain and are often combined with opioids for treating cancer. It is assumed that this combination may heighten somnolence and respiratory depression due to the inhibitory effects of opioids on the central nervous system. Although pregabalin, a gabapentinoid, is known to increase somnolence frequency during opioid therapy, whether mirogabalin exerts similar effects on somnolence frequency under opioid therapy remains unknown. This study examined the signals of somnolence and respiratory depression in response to pregabalin and mirogabalin use by utilizing data from the Japanese Adverse Drug Event Report database and assessed their interaction with strong opioid analgesics. Information was obtained from the JADER database from April 2004 to August 2023 via the Pharmaceuticals and Medical Devices Agency website. The study focused on neuropathic pain medications, specifically "pregabalin" and "mirogabalin besilate." Adverse events were defined using preferred terms (PTs) from the Medical Dictionary for Regulatory Activities version 26.1. The PTs considered were "Somnolence (10041349)" and "Respiratory depression (10038678)." To investigate the effect of the combination of strong opioid analgesics with pregabalin and mirogabalin on the occurrence of somnolence, a multivariable logistic regression analysis was conducted. Signals for somnolence were detected with the use of both drugs (pregabalin: information component (IC) [95% confidence intervals (CIs)]: 2.89 [2.70 to 3.08]; mirogabalin: IC [95% CIs] 2.50 [1.85 to 3.16]). When evaluating respiratory depression, a typical and serious adverse event of opioid analgesic use, a signal was detected with pregabalin use but not with mirogabalin use (pregabalin: (IC [95% CIs] 1.28 [0.83 to 1.73]; mirogabalin: IC [95% CIs] -0.15 [-2.20 to 1.89]). Multivariable analysis indicated that the use of strong opioid analgesics increased the occurrence of somnolence when combined with pregabalin but not when combined with mirogabalin ( = 0.004). While the safety of concomitant administation of mirogabalin with opioids remains controversial, caution should be exercised when using pregabalin, especially in combination with opioids for neuropathic pain, compared to that for mirogabalin.
加巴喷丁类抗惊厥药是治疗神经病理性疼痛的标准治疗方法，常与阿片类药物联合用于治疗癌症。据推测，这种联合用药可能会因阿片类药物对中枢神经系统的抑制作用而增加嗜睡和呼吸抑制。虽然加巴喷丁类药物普瑞巴林在阿片类药物治疗期间已知会增加嗜睡频率，但米罗加巴林在阿片类药物治疗下是否会对嗜睡频率产生类似影响尚不清楚。本研究利用日本不良事件报告数据库的数据，通过评估加巴喷丁和米罗加巴林对阿片类药物治疗时的镇静和呼吸抑制信号及其与强阿片类镇痛药的相互作用，来研究这些药物的信号。信息来自 2004 年 4 月至 2023 年 8 月通过药品和医疗器械管理局网站从 JADER 数据库中获取。本研究主要关注神经病理性疼痛药物，具体为“普瑞巴林”和“米罗加巴林苯磺酸盐”。不良事件使用监管活动医学词典 26.1 版的首选术语（PTs）定义。考虑的 PTs 是“嗜睡（10041349）”和“呼吸抑制（10038678）”。为了研究强阿片类镇痛药与普瑞巴林和米罗加巴林联合使用对嗜睡发生的影响，进行了多变量逻辑回归分析。使用两种药物（普瑞巴林：信息成分（IC）[95%置信区间（CIs）]：2.89[2.70 至 3.08]；米罗加巴林：IC[95% CIs]2.50[1.85 至 3.16]）检测到镇静信号。当评估阿片类药物使用的典型和严重不良事件呼吸抑制时，仅在使用普瑞巴林时检测到信号，而在使用米罗加巴林时未检测到信号（普瑞巴林：（IC[95% CIs]1.28[0.83 至 1.73]；米罗加巴林：IC[95% CIs]-0.15[-2.20 至 1.89]）。多变量分析表明，与米罗加巴林相比，强阿片类镇痛药与普瑞巴林联合使用会增加嗜睡的发生（ = 0.004）。虽然米罗加巴林与阿片类药物同时使用的安全性仍存在争议，但与米罗加巴林相比，在使用普瑞巴林治疗神经病理性疼痛时应格外小心。
