USA: Study on Levothyroxine Switching

Conflicting the current guidelines on the management of hypothyroidism, a recent study in JAMA Internal Medicine has revealed that switching from one generic levothyroxine preparation to another is not associated with significant changes in TSH level. The current guideline recommendation warns clinicians about potential changes in serum thyrotropin (TSH) levels associated with switching among levothyroxine products sourced from different manufacturers.

"We found no statistically significant differences in TSH levels among propensity-matched patients who were or were not switched from one generic form of levothyroxine to another," Juan P. Brito, Mayo Clinic, Rochester, Minnesota, and colleagues wrote in their study.

Switching among generic levothyroxine sodium products made by different manufacturers typically occurs at the pharmacy and may affect TSH levels. Considering this, Dr. Brito and the team aimed to compare TSH levels between patients who continued taking the same sourced generic levothyroxine product and those who switched in a comparative effectiveness research study.

The study with 1:1 propensity matching used data from OptumLabs Data Warehouse, a national administrative claims database linked to laboratory test results. It included adults aged 18 years or older if they filled a generic levothyroxine prescription between January 1, 2008, and June 30, 2019, and had a stable drug dose, the same drug manufacturer, and a normal TSH level (0.3-4.4 mIU/L) for at least 3 months before either continuing to take the same product or switching among generic levothyroxine products (index date).

Those who were pregnant, had a diagnosis of hypopituitarism or hyperthyroidism, or had a medical condition or used medications that could affect thyrotropin levels were excluded. Also, if they filled a prescription for other forms of thyroid replacement therapy between 6 months before the index date and when the first TSH level was obtained 6 weeks to 12 months after the index date, they were excluded. Data analysis was done from December 1, 2019, to November 24, 2021.

Main outcome and measures included a percentage of people with a normal (0.3-4.4 mIU/L) or markedly abnormal (<0.1 or >10.0 mIU/L) TSH level using the first available laboratory result 6 weeks to 12 months after the index date.

Key Findings

• A total of 15,829 patients filled generic levothyroxine (mean age, 58.9 years; 73.4% were women; 4.5% were Asian, 10.2% were Black, 11.4% were Hispanic, and 71.4% were White individuals); of these patients, 56.3% received a daily levothyroxine dose of 50 μg or less.
• A total of 13,049 patients (82.4%) continued taking the same sourced preparation, and 2,780 (17.6%) switched among generic levothyroxine preparations.
• Among 2,780 propensity-matched patient pairs, the proportion of patients with a normal TSH level after the index date was 82.7% among nonswitchers and 84.5% among switchers (risk difference, −0.018).
• The proportion of patients with a markedly abnormal TSH level after the index date was 3.1% (87) among nonswitchers and 2.5% (69) among switchers (risk difference, 0.007).
• The mean TSH levels after the index date were 2.7 mIU/L among nonswitchers and 2.7 mIU/L among switchers.

"Results from the study suggest that switching among different generic levothyroxine products was not associated with clinically significant changes in TSH level," wrote the authors. "They are in conflict with the current guideline recommendation that warns clinicians about potential changes in TSH level associated with switching among levothyroxine products sourced from different manufacturers."

Reference

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

Keywords

JAMA, hypothyroidism, serum thyrotropin, generic, Juan P Brito, TSH