Ebisu Pharmacy, Osaka-shi, Japan.
Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, Higashi-osaka, Japan.
J Clin Pharm Ther. 2020 Feb;45(1):65-71. doi: 10.1111/jcpt.13024. Epub 2019 Aug 10.
Amiodarone (AMD) treatment is associated with a number of significant adverse effects including thyroid dysfunction. However, the relationship between the development of thyroid dysfunction and the dosage and treatment duration of AMD remains unclear. The purpose of this study was to examine the onset profiles of amiodarone-associated thyroid dysfunction using a spontaneous adverse drug reaction (ADR) reporting database.
Data were obtained from the US Food and Drug Administration Adverse Event Reporting System (FAERS). For signal detection of spontaneous ADRs, the reporting odds ratio (ROR) and information component (IC) were calculated. Cumulative incidences of hyperthyroidism and hypothyroidism were assessed using the Kaplan-Meier method, and time-to-onset profiles were analysed using the Weibull shape parameter (WSP) test.
The median time-to-onset of hyperthyroidism associated with AMD and other drugs was 720.0 (range: 225.5-1145.0) and 101.5 (range: 14.0-468.8) days, respectively. Patients treated with AMD showed a significantly longer time-to-onset of hyperthyroidism than those treated with other drugs (P < .001). The median time-to-onset of hypothyroidism associated with AMD and other drugs was 183.0 (range: 35.0-727.8) and 153.0 (range: 19.0-608.0) days, respectively. There was no significant difference in the time-to-onset of hypothyroidism between patients treated with AMD and those treated with other drugs (P = .13). For hyperthyroidism, the WSP test showed that AMD had a wear-out failure-type profile and other drugs had early failure-type profiles. For hypothyroidism, the WSP test showed that both AMD and other drugs had early failure-type profiles.
Amiodarone-associated hyperthyroidism had a different onset profile than hyperthyroidism associated with other drugs. Because the time-to-onset of AMD-associated hyperthyroidism is widely distributed, sustained and continuous attention is required to detect and treat hyperthyroidism during AMD treatment. In contrast, AMD-associated hypothyroidism had an onset profile that was similar to that of other drugs, suggesting that attention should be focused on the earlier stages of treatment.
胺碘酮（AMD）治疗与许多重大不良反应有关，包括甲状腺功能障碍。然而，甲状腺功能障碍的发展与 AMD 的剂量和治疗时间之间的关系尚不清楚。本研究的目的是使用自发药物不良反应（ADR）报告数据库检查胺碘酮相关甲状腺功能障碍的发病情况。
数据来自美国食品和药物管理局不良事件报告系统（FAERS）。为了检测自发 ADR 的信号，计算了报告比值比（ROR）和信息成分（IC）。使用 Kaplan-Meier 方法评估甲状腺功能亢进和甲状腺功能减退的累积发生率，并使用威布尔形状参数（WSP）测试分析发病时间曲线。
与 AMD 和其他药物相关的甲状腺功能亢进的中位发病时间分别为 720.0（范围：225.5-1145.0）和 101.5（范围：14.0-468.8）天。与其他药物治疗的患者相比，接受 AMD 治疗的患者的甲状腺功能亢进发病时间明显延长（P <.001）。与 AMD 和其他药物相关的甲状腺功能减退的中位发病时间分别为 183.0（范围：35.0-727.8）和 153.0（范围：19.0-608.0）天。接受 AMD 治疗的患者与接受其他药物治疗的患者之间甲状腺功能减退的发病时间无显著差异（P =.13）。对于甲状腺功能亢进，WSP 测试表明 AMD 具有磨损故障类型的特征，而其他药物具有早期故障类型的特征。对于甲状腺功能减退，WSP 测试表明 AMD 和其他药物均具有早期故障类型的特征。
胺碘酮相关的甲状腺功能亢进的发病特征与其他药物相关的甲状腺功能亢进不同。由于 AMD 相关甲状腺功能亢进的发病时间分布广泛，因此在 AMD 治疗期间需要持续关注并检测和治疗甲状腺功能亢进。相比之下，AMD 相关的甲状腺功能减退的发病特征与其他药物相似，这表明应在治疗的早期阶段关注。
