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Exp Clin Endocrinol Diabetes 2021; 129(12): 908-917
DOI: 10.1055/a-1302-9343
Article

Comparison of Safety Profiles of the New and Old Formulations of Levothyroxine in a First Global Introduction in France

Hendrik Lehnert
1   Center of Brain, Behavior and Metabolism, University of Luebeck, Lübeck, Germany
2   University of Salzburg, Austria
,
Claire Castello-Bridoux
3   Merck Santé S.A.S., Lyon, France
,
Bushan Channaiah
4   Merck KGaA, Darmstadt, Germany
,
Karine Martiniere
3   Merck Santé S.A.S., Lyon, France
,
Steven Hildemann
4   Merck KGaA, Darmstadt, Germany
,
Jean-Louis Wémeau
5   Department of Endocrinology, University of Lille, Lille, France
› Author Affiliations Funding: This study was funded by Merck KGaA (Darmstadt, Germany).
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Abstract

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.

Supplementary Material



Publication History

Received: 17 September 2019
Received: 03 November 2020

Accepted: 28 January 2021

Article published online:
28 January 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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