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Levothyroxine: problems caused by a change in formulation were foreseeable

The specificities of levothyroxine mean that it was foreseeable that a change in formulation would require a careful rebalancing of the treatment for some patients.

Following a change in the formulation of Levothyrox° tablets in France in March 2017, thousands of patients reported suffering from various disorders which they believed were related to the new brand. This change was requested by the French medicines agency in 2012, to reduce the fluctuations in levothyroxine content in tablets over time and from one batch to another. These fluctuations are sometimes harmful because levothyroxine has a narrow therapeutic margin, requiring a very precise individual adjustment of the dosage with careful monitoring of the signs and symptoms, as well as the plasma thyroid stimulating hormone (TSH) assay. Determining the optimal dosage takes time because levothyroxine is eliminated slowly from the body; during a change of dosage, it takes approximately 5 weeks to establish a new equilibrium.

Pharmacokinetic and pharmaceutical quality studies, and previous replacement of one levothyroxine-based brand with another, show weaknesses in the old formulation, the benefits of the new, and the fact that it was foreseeable that some patients would be affected for several weeks or months in switching from one to the other.

The first results of the pharmacovigilance survey, concerning about 5000 cases reported in the French pharmacovigilance database between March and September 2017, do not show any new adverse effects of the new formulation.

In short, the specificities of levothyroxine made it possible to anticipate that a change of formulation would require a careful rebalancing of treatment dosage of certain patients. It is regrettable that patients and healthcare professionals were not properly informed.

©Prescrire 1 February 2018

"Levothyroxine: predictable disorders caused by a change in formulation" Prescrire Int 2018; 27 (190): 45-46. (Pdf, subscribers only).

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For more information:

Lévothyrox° (levothyroxine):
a change in formulation results
in thousands of reports of
adverse effects
(September 2017)