Center for Experiential Pharmacy Practice, School of Pharmacy, Tokyo University of Pharmacy and Life SciencesTokyo, Japan.
Department of Practical Pharmacy, Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Chiba, Japan.
J Pharm Pharm Sci. 2022;25:245-252. doi: 10.18433/jpps32908.
Everolimus-induced diabetes mellitus (DM) outcomes include everolimus-resistant tumors and poor hyperglycemia outcomes, which lead to various other negative clinical outcomes. This study aimed to evaluate the effect of associations between concomitant drug treatment and time to DM event occurrence (onset or exacerbation) on the outcomes of everolimus-induced DM in patients with cancer.
Data from the Japanese Adverse Drug Event Report database (JADER) were used, and patient drug use, time of DM event occurrence, and DM outcomes were determined from patient records. Associations between concomitant drug groups with everolimus and DM event occurrence were then evaluated for patients with both good and poor DM outcomes.
Top ten groups used concomitantly were drugs for the treatment of hypertension (HT), controlled DM, constipation, hypothyroidism, kidney disease, insomnia, hyperlipidemia, hyperuricemia, anemia, and gastritis. Among them, only HT, controlled DM, and hyperlipidemia were associated with DM event occurrence. These three drug groups were examined by the outcome of everolimus concomitant usage and revealed a significantly shorter time to DM event occurrence for patients with poor outcomes than for those with good outcomes (p = 0.015) among patients without a concomitant drug for DM. Each of these three drug groups was analyzed on patients who were concomitantly administered with one of each drug group with everolimus and revealed a significantly shorter time to DM event occurrence for patients with poor outcomes than for those with good outcomes in patients who received concomitant HT drugs (p = 0.006). Moreover, among the four HT drug categories, calcium channel blockers were significantly associated with poor outcomes (odds ratio, 2.18 [1.09-4.34], p = 0.028).
To prevent everolimus-induced poor DM outcomes, early DM detection and treatment are necessary, and the effect of the concomitant drug should be considered before initiating everolimus treatment.
依维莫司引起的糖尿病（DM）的结局包括依维莫司耐药肿瘤和血糖控制不佳，这会导致各种其他负面临床结局。本研究旨在评估伴随药物治疗与 DM 事件（发病或恶化）发生时间之间的关联对癌症患者中依维莫司引起的 DM 结局的影响。
使用日本不良药物事件报告数据库（JADER）的数据，从患者记录中确定患者的药物使用、DM 事件发生时间和 DM 结局。然后评估伴用药物与 DM 事件发生之间的关联，对 DM 结局良好和不佳的患者分别进行评估。
前十大伴用药物组为治疗高血压（HT）、控制 DM、便秘、甲状腺功能减退、肾病、失眠、高血脂、高尿酸血症、贫血和胃炎的药物。其中，只有 HT、控制 DM 和高血脂与 DM 事件发生相关。对这些三组药物进行了依维莫司伴随使用的结局检查，结果显示，在无 DM 伴随药物的患者中，DM 结局不佳的患者比 DM 结局良好的患者 DM 事件发生时间更短（p = 0.015）。在接受依维莫司和一种伴用药物的患者中，对这三组药物进行了分析，结果显示，DM 结局不佳的患者比 DM 结局良好的患者 DM 事件发生时间更短（p = 0.006）。在这四种 HT 药物类别中，钙通道阻滞剂与不良结局显著相关（比值比，2.18[1.09-4.34]，p = 0.028）。
为了预防依维莫司引起的不良 DM 结局，需要早期检测和治疗 DM，并在开始依维莫司治疗前考虑伴随药物的影响。
