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

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.

Survey of Clinical Practice Patterns in the Management of 992 Hyperthyroid Patients in France.

BACKGROUND: Considerable variations in diagnosis and therapeutic practices are reported for hyperthyroidism (HT) between countries. METHODS: A clinical study was conducted among a representative sample of 263 endocrinologists in France. All consecutive patients seen for HT during the study period were included. Diagnosis and treatment modalities were recorded from hyperthyroid patients with Graves disease (GD, n = 802), multinodular goiter (MNG, n = 121), and toxic adenoma (TA, n = 69). RESULTS: Antithyroid antibodies were measured in half of the population (anti-TPO in 48.5% and anti-TSH receptor in 57.8%). Patients had thyroid ultrasonography and scintigraphy in 93.8 and 40.3%, respectively. Therapeutic management depended on the etiology: for the first episode of GD, antithyroid drugs (ATDs) were the first-line treatment in 91% of the patients, combined with surgery in 6.1% and with radioiodine in 2.9%. Surgery was preferred to radioiodine in MNG (52.6 vs. 22.4%) and TA (59.1 vs. 24.2%). Euthyroid status was achieved after 3 months in 64.4% of GD. A "block and replace" protocol was used in 41.2% of patients. After 3 months, 73% of patients were euthyroid in the "block and replace" group compared to 56.2% in the group with ATDs alone (p = 0.009). For MNG and TA, more than 75% of patients were euthyroid at the 3-month follow-up. CONCLUSIONS: Large discrepancies remain between clinical practice and international guidelines. These results should boost efforts to improve adherence to these guidelines.