New study addresses levothyroxine dosing concern

The question of generic equivalency of levothyroxine products has remained unanswered for several decades. But a new study led by Mayo Clinic researchers found that for patients with predominantly benign thyroid disease and newly treated hypothyroidism, there were no differences in cardiovascular event risks between patients treated with brand or generic levothyroxine.

Using a large, national data repository, researchers reviewed the records of approximately 88,000 patients, divided equally in half based on the initiation of generic or brand levothyroxine. Examining the two cohorts and the number of hospitalizations for heart attacks, congestive heart failure, atrial fibrillation, or strokes, the research team did not find any difference in the event rates for the four types of cardiovascular events.

However, according to Robert Smallridge, MD, from Mayo Clinic in Jacksonville, FL, and lead author of the study, there were two major limitations: the lack of information on thyroid lab results while patients were on thyroid hormone, and the short duration of follow-up (the average was 1 year).

“If there were no differences in TSH [thyroid-stimulating hormone] values between cohorts, then one would not expect a difference in outcomes, and the follow-up may have been too short to elicit atrial fibrillation and subsequent cardiovascular events,” said Smallridge.

Smallridge added that he was surprised by the short average duration of follow-up available for a prescription that is required for life. Levothyroxine is the most prescribed medication in the United States, with more than 23 million prescriptions written, according to the study, which was published in the July issue of Mayo Clinic Proceedings.

“The results should be regarded as preliminary, given the short mean duration of follow-up,” said Smallridge.

Prior research has linked hypothyroidism to cardiovascular risk, but prompt treatment is known to improve a patient’s lipid panel results and all-around mortality. The American Thyroid Association and the American Association of Clinical Endocrinologists both recommend levothyroxine for routine treatment of hypothyroidism for many reasons, including its affordable costs and favorable adverse effect profile for most patients.

In an October 2018 Medscape editorial, Angela M. Leung, MD, MSc, an endocrinologist at UCLA Health, said the concern about dose equivalency between generic and brand formulations of levothyroxine is mostly historical. FDA now requires synthetic thyroxine (T4) in levothyroxine to be within 5% of the stated dose, making both brand and generic therapeutically interchangeable, like most other brand and generic prescriptions.

Lyndsy Beckman, PharmD, pharmacy quality and patient safety chief from Kaiser Permanente in Hyattsville, MD, was not surprised by the results of the Mayo Clinic study.

“I believe that the FDA and manufacturers of generic medications strive to ensure generic products are just as safe and effective as their brand counterparts,” she said. “This study helps to show that, even for narrow therapeutic index medications, the same patient outcomes and expectation can be achieved.”

According to the study authors, FDA “has declared that generics are equivalent (and often less expensive), so insurers may charge higher prices and require higher co-payments for branded [levothyroxine].” Authors also noted that more physicians are prescribing generic levothyroxine. In 2013, 63% of endocrinologists and 73% of primary care physicians prescribed generic levothyroxine.

“This study helps to show that, even for narrow therapeutic index medications, the same patient outcomes and expectation can be achieved.”

For the full article, please visit www.pharmacytoday.org for the September 2019 issue of Pharmacy Today.