Background Levothyroxine sodium marketed in France was reformulated following a French National Agency for Medicines and Health Products Safety request for a more stringent potency specification. Despite previously established purity and bioequivalence of the new and old formulations, reports of adverse events substantially increased following reformulation. This analysis evaluated the nature and relevance of the medically confirmed safety reports. Methods Spontaneous and solicited individual case safety reports in France were retrieved from 26 March 2015 to 30 June 2016 (old formulation) and 26 March 2017 to 30 June 2018 (new formulation). Rates of reports and adverse events were calculated for the overall patient population and for at-risk subgroups. Adverse events delineated by thyroid-stimulating hormone levels were evaluated. Results A total of 295 and 42 775 reports for the old formulation and new formulation, respectively, were retrieved, with 149 and 5503 medically confirmed. The most common medically confirmed adverse events were consistent with the known safety profile of levothyroxine, with generally comparable rates between both formulations (range of differences, 1.8–4.1%). Most cases were not serious (old formulation, 65.8%; new formulation, 78.7%). Reporting rates were similar or higher for the old formulation within subgroups of at-risk patients. Nature/distributions of adverse events by thyroid-stimulating hormone levels as determined by both the marketing authorization holder of levothyroxine and the French National Agency for Medicines and Health Products Safety were similar. Conclusions The new formulation safety profile aligns with the established profile of the old formulation of levothyroxine. The benefit–risk profile is unchanged, such that the benefits of using the new formulation in the approved indications outweigh the risks associated with the treatment.

中文翻译：

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法国首次全球引进左甲状腺素新旧制剂的安全性比较

背景 在法国销售的左甲状腺素钠是根据法国国家药品和健康产品安全局对更严格的效力规格的要求重新配制的。尽管先前已确定新旧配方的纯度和生物等效性，但在重新配方后，不良事件的报告显着增加。该分析评估了医学确认的安全报告的性质和相关性。方法 检索自 2015 年 3 月 26 日至 2016 年 6 月 30 日（旧版）和 2017 年 3 月 26 日至 2018 年 6 月 30 日（新版）在法国自发和征求的个人病例安全报告。计算了整个患者群体和高危亚组的报告率和不良事件发生率。评估了由促甲状腺激素水平描述的不良事件。结果共检索到旧剂型和新剂型的报告295份和42775份，其中经医学证实的149份和5503份。最常见的医学证实的不良事件与已知的左甲状腺素安全性一致，两种制剂的发生率大致相当（差异范围，1.8-4.1%）。大多数病例并不严重（旧配方，65.8%；新配方，78.7%）。在高危患者亚组中，旧配方的报告率相似或更高。由左旋甲状腺素的上市许可持有人和法国国家药品和健康产品安全局确定的促甲状腺激素水平的不良事件的性质/分布相似。结论 新配方的安全性特征与左甲状腺素旧配方的既定特征一致。收益-风险概况没有改变，因此在批准的适应症中使用新制剂的收益超过了与治疗相关的风险。