Switching generic levothyroxine preparations does not affect thyroid hormone levels
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Adults who switch generic levothyroxine preparations from one manufacturer to another do not have a difference in mean thyroid-stimulating hormone levels compared with those who do not switch, according to study data.
According to guidelines published by the American Thyroid Association in 2014, providers are advised to avoid switching among generic levothyroxine products from different manufacturers. Juan P. Brito, MD, MSc, associate professor of medicine and consultant in the division of endocrinology at the Mayo Clinic in Rochester, Minnesota, said the guidelines have led providers to prescribe brand-name levothyroxine for most adults with hypothyroidism because physicians are unable to keep track of when pharmacies switch generic products.
“We decided to do this study to test whether switching among generic levothyroxine products have any effect on thyroid hormone values,” Brito told Healio. “In those who switch, we don’t see an impact on thyroid hormone levels compared with people who did not switch. This sends a signal that switching is safe and keeping patients on generic levothyroxine doesn’t have a significant impact on thyroid hormone values.”
Brito and colleagues conducted a retrospective study of deidentified administrative claims data from 2008 to June 2019 in the OptumLabs Data Warehouse, a database that includes people enrolled in commercial insurance and Medicare Advantage programs across the U.S. Researchers included 15,829 adults who filled a generic levothyroxine prescription from Mylan, Sandoz or Lannett (mean age, 58.9 years; 73.4% women, 71.4% white). Adults with a stable prescription dose from the same manufacturer and a normal TSH level between 0.3 mIU/L and 4.4 mIU/L for at least 3 months were included in the analysis. TSH levels were collected from those who used the same generic prescription from a random fill date within a year of their first fill data, and from the date of switching for adults who changed preparations.
The findings were published in JAMA Internal Medicine.
Of the study cohort, 82.4% continued taking the same generic preparation during the study period, and 17.6% switched at least once. The 2,780 adults who switched were paired with an adult in the nonswitching group using propensity score-matching. Among the matched pairs, the percentage of adults with a normal TSH between 0.3 mIU/L and 4.4 mIU/L was similar between switchers (84.5%) and nonswitchers (82.7%). Similarly, the proportion of adults with markedly abnormal TSH levels of less than 0.1 mIU/L or greater than 10 mIU/L was similar for switchers (2.5%) and nonswitchers (3.1%). Mean TSH levels were 2.7 mIU/L in both groups.
In a subgroup of 364 adults receiving more than 100 g of levothyroxine daily, there was no significant difference between switchers and nonswitchers in the percentage of those with normal TSH levels. There were also no associations observed in sensitivity analysis.
Brito said the findings provide evidence for the ATA to update its recommendations to allow generic levothyroxine switching, noting the change can have a significant cost savings for patients currently taking brand-name preparations.
“Levothyroxine is one of the most prescribed medications in the U.S.,” Brito said. “It’s a huge market, and prescribing only brands is a significant expense to the health care system and the patients as well.
“Clinicians should not give patients a brand name just because they have concerns about switching,” Brito added. “They should revise the recommendation that we keep the patients on the same product.”
For more information:
Juan P. Brito, MD, MSc, can be reached at brito.juan@mayo.edu.
Perspective
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Jonathan D. Leffert, MD, FACP, FACE, ECNU
The study by Brito and colleagues on switching generic preparations of levothyroxine provides new data on this old topic and much food for thought. Brito and colleagues looked retrospectively at over 15,000 patients taking generic levothyroxine preparations to determine if switching preparations in this group of patients made a difference in their thyroid-stimulating hormone level. They found that among the switchers and nonswitchers, approximately 85% in each group maintained their TSH in the normal range. In each group, those with the highest and lowest TSH levels were also made up about the same proportion (3%). The conclusion of the study is that switching did not seem to make a difference in the TSH levels among patients on generic levothyroxine, and thus the current American Thyroid Association guidelines to avoid switching brand name preparations for generic preparations should be revised.
My initial concern with the conclusions of this study is this retrospective group included only patients on generic preparations, so it did not address the guideline concern about switching from brand name to generics. Secondly, the study did not include patients who are pregnant, a group in which trimester-specific TSH levels are required to ensure a good outcome. Other patients with specific thyroid disorders, such as those with thyroid cancer requiring suppression of their TSH and patients with secondary hypothyroidism due to pituitary disorders, also were not included in this cohort of patients.
Finally, Brito and colleagues previously examined this same database and found that 30% of the patients had normal thyroid function prior to initiating thyroid hormone. Because patients with normal pre-treatment TSH levels would not be likely to exhibit much in the way of change between different generic preparations, patients with normal thyroid function pre-treatment would more than likely have the same post-treatment thyroid function regardless of the preparation used to treat. In this present study, it was unclear if this database included only hypothyroid patients on treatment or patients with normal thyroid function on treatment.
As endocrinologists, we see patients with a wide variety of thyroid hormone replacement needs, which call for a range of thyroid hormone replacements. Our guidelines provide the flexibility to use thyroid hormone replacements based upon the clinical situation. These clinical situations, as stated in the guideline, include thyroid cancer patients, frail patients and those with congenital hypothyroidism. I would include pregnant patients and those with secondary hypothyroidism in which T4 levels would be most commonly used as a guide to therapy.
In order for guidelines to change, the evidence should be a moderate or high quality, which requires randomized clinical trials rather than retrospective studies, and the patient population should have documented hypothyroidism on replacement therapy.
In the final analysis, this study has raised some interesting questions regarding the important topic of switching between generic levothyroxine preparations. Before treatment guidelines can be changed, we will need more data on the special groups of patients, such as pregnant and thyroid cancer patients, studies that reinforce the equivalence of brand name and generic preparations of levothyroxine, and randomized controlled trials of hypothyroid patients on replacement therapy who have undergone switching of their therapy.
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