Switching Among Generic Levothyroxine Does Not Alter Thyrotropin Levels

Diseased thyroid gland, conceptual computer illustration.
A team of investigators assessed the impact of switching among generic levothyroxine products on thyrotropin levels.

Results of a comparative effectiveness research study conflicted with current guideline recommendations, finding that switching between different generic levothyroxine preparations did not alter serum thyrotropin levels. These findings were published in JAMA Internal Medicine.

Administrative claims data from the OptumLabs Data Warehouse were analyzed for this study. Patients who filled prescriptions for generic levothyroxine between 2008 and 2019 were assessed for changes in thyrotropin levels after switching between preparations after at least 3 months of use. To account for baseline differences, patients who switched preparations (n=2780) were matched 1:1 with those who did not switch preparations (n=2780).

The mean ages for those who switched preparations and those who did not were 58.6 and 58.6 years, respectively; 72.6% and 73.4% were women, 71.9% and 72.4% were White, Charlson Comorbidity Index was 1.0 and 1.0, and mean duration of levothyroxine use was 225.5 and 227.7 days, respectively.

The proportion of patients who had normal thyrotropin levels between 6 weeks and 12 months of the index date was 84.5% among those who switched preparations and 82.7% among those who did not switch (risk difference [RD], -0.018; 95% CI, -0.038 to 0.002; P =.07). Similarly, no significant differences were observed for the proportion of patients with abnormal (P =.07) or markedly abnormal (P =.14) thyrotropin levels.

Stratified by dose, a similar proportion of patients had normal thyrotropin levels among the cohort with levothyroxine doses greater than 100 mg (RD, -0.058; 95% CI, -0.122 to 0.006; P =.08) and up to 100 mg (RD, -0.012; 95% CI, -0.032 to 0.009; P =.26). No differential trends were observed in the sensitivity analysis.

This study was limited by not including branded levothyroxine products; it remains unclear whether generic-to-branded or branded-to-generic switching may disrupt thyrotropin levels.

Contrary to current guideline recommendations, this study found no evidence that switching between generic levothyroxine products has a significant clinical effect on thyrotropin levels. These findings should be confirmed among an independent cohort, and recommendations may need to be updated.

Disclosure: Multiple study authors declared affiliations with the biotech or pharmaceutical industries. Please see the original reference for a full list of authors’ disclosures.


Brito JP, Deng Y, Ross JS, et al. Association between generic-to-generic levothyroxine switching and thyrotropin levels among US adults. JAMA Intern Med. Published online February 28, 2022. doi:10.1001/jamainternmed.2022.0045