Tomida Takeshi, Kimura Takeshi, Yamamoto Kazuhiro, Uda Atsushi, Matsumoto Yuki, Tamura Naoki, Iida Masashi, Tanifuji Akiko, Matsumoto Kumiko, Mizuta Naomi, Ebisawa Kei, Ohji Goh, Omura Tomohiro, Iwata Kentaro, Yano Ikuko
Department of Pharmacy, Kobe University Hospital, 7-5-2 Kusunoki-Cho, Chuo-Ku, Kobe, 650-0017, Japan.
Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8558, Japan.
J Pharm Health Care Sci. 2024 Sep 3;10(1):54. doi: 10.1186/s40780-024-00376-4.
While nirmatrelvir/ritonavir (NMV-r) has been positioned as a first-line treatment for mild to moderate COVID-19, it has multiple and significant drug-drug interactions (DDIs). The use of NMV-r in Japan has been limited compared to the United States. This study aimed to describe the distribution of DDIs with NMV-r and their management in patients with COVID-19 under the control of a management system for the appropriate use of NMV-r.
A retrospective observational study was conducted at a Japanese university hospital. The management system included a flowchart for selecting antivirals and a list for reviewing DDI management, based on the National Institutes of Health guidelines and the guidance of the Japanese Society of Pharmaceutical Health Care and Sciences. Patients with mild to moderate COVID-19 and prescribed NMV-r or molnupiravir (MOV) were included. The primary outcome was DDI management practices, including the selected COVID-19 medications. The secondary outcome included the distribution of DDI classification and the 30-day all-cause mortality.
This study included 241 patients (median age of 60 years, 112 [46.5%] females), of whom 126 and 115 received NMV-r and MOV, respectively. Of the 241 patients, 145 (60.2%) received concomitant medications that have DDIs with NMV-r. All 30 patients with severe renal impairment or insufficient details on concomitant medications received MOV. Forty-nine patients with concomitant medications required alternative COVID-19 therapy consideration due to DDIs, of whom 42 (85.7%) patients received MOV. Eighty-one patients had concomitant medications requiring temporary adjustment, of whom 44 (54.3%) patients received NMV-r, and 42 of these patients temporarily adjusted these concomitant medications. Five patients with concomitant medications that can continued by monitoring the effects/adverse effects, of whom 4 (80.0%) patients received NMV-r. Seventy-six patients without concomitant medications requiring DDI management, of whom 71 (93.4%) patients received NMV-r. The 30-day all-cause mortality for eligible patients was 0.9% [95% confidence interval, 0.1-3.1].
Most patients received appropriate antivirals according to the classification of DDIs, and most patients with concomitant medications requiring temporary adjustment received the recommended DDI management. Our management system is effective in promoting the use of NMV-r in the appropriate patients and managing problematic DDIs.
虽然奈玛特韦/利托那韦（NMV-r）已被定位为轻度至中度新冠病毒病（COVID-19）的一线治疗药物，但它存在多种显著的药物相互作用（DDIs）。与美国相比，NMV-r在日本的使用受到限制。本研究旨在描述在NMV-r合理使用管理系统的控制下，COVID-19患者中NMV-r的药物相互作用分布情况及其管理。
在一家日本大学医院进行了一项回顾性观察研究。该管理系统包括根据美国国立卫生研究院指南和日本药物保健与科学协会的指导制定的抗病毒药物选择流程图和药物相互作用管理审查清单。纳入轻度至中度COVID-19且开具NMV-r或莫努匹拉韦（MOV）的患者。主要结局是药物相互作用管理实践，包括所选的COVID-19治疗药物。次要结局包括药物相互作用分类分布和30天全因死亡率。
本研究纳入241例患者（中位年龄60岁，女性112例[46.5%]），其中126例和115例分别接受了NMV-r和MOV治疗。在241例患者中，145例（60.2%）接受了与NMV-r存在药物相互作用的伴随用药。所有30例严重肾功能损害或伴随用药细节不足的患者均接受了MOV治疗。49例有伴随用药的患者因药物相互作用需要考虑改用其他COVID-19治疗方法，其中42例（85.7%）患者接受了MOV治疗。81例有伴随用药的患者需要临时调整用药，其中44例（54.3%）患者接受了NMV-r治疗，且其中42例患者对这些伴随用药进行了临时调整。5例有伴随用药且可通过监测疗效/不良反应继续用药的患者，其中4例（80.0%）患者接受了NMV-r治疗。76例无需要进行药物相互作用管理的伴随用药的患者，其中71例（93.4%）患者接受了NMV-r治疗。符合条件患者的30天全因死亡率为0.9%[95%置信区间，0.1 - 3.1]。
大多数患者根据药物相互作用分类接受了适当的抗病毒药物治疗，大多数需要临时调整伴随用药的患者接受了推荐的药物相互作用管理。我们的管理系统在促进NMV-r在合适患者中的使用以及管理有问题的药物相互作用方面是有效的。
