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.
