UPDATED: FDA and its research take aim at thyroid association's guideline on not using levothyroxine generics
Generic drugs represent the vast majority of all drugs prescribed in the US.
But in some unique cases, the FDA acknowledges that there are doctors who are concerned about drugs with a narrow therapeutic window (i.e., as the FDA says, “drugs where small differences in dose or blood concentration may lead to serious therapeutic failures or adverse drug reactions”), and therefore may be more likely to prescribe brand-name products over generics in some cases.
But in one instance, where the American Thyroid Association (ATA) recommends that generics not be used in some instances when the thyroid hormone levothyroxine is used, the FDA is now pointing to new FDA-funded real-world research that shows how switching between generics proved to be similar to sticking with the brand-name counterpart.
For the study, the researchers dove into an administrative claims database that linked lab test measures of thyroid function of patients undergoing treatment for hypothyroidism with levothyroxine, identifying and matching two different populations to compare the effects of generic switching to single-product use.
“Their conclusion is that switching among different generic levothyroxine products was not associated with clinically significant changes in thyroid function (as indicated by subgroup average serum thyrotropin level). The researchers’ conclusion — although fully consistent with FDA precepts of bioequivalence and, at the pharmacy level, product interchangeability itself — conflicts with current ATA guideline recommendations that warn clinicians about potential changes in thyroid function associated with levothyroxine product switching,” the agency explained yesterday.
Prior to initiating this study, the researchers, including some from the Mayo Clinic and FDA, noted how the ATA even questioned the FDA’s methods for determining bioequivalence between levothyroxine products.
And while the ATA guidelines recommend using thyrotropin levels as the biomarkers for evaluating therapeutic equivalence, in the absence of such evidence the ATA recommends that prescribers avoid switching between levothyroxine products in the treatment of hypothyroid patients. As a result of that recommendation, brand-name levothyroxine was preferentially prescribed over generic levothyroxine products, the FDA explains.
“Results of this comparative effectiveness research study suggest that switching among different generic levothyroxine products was not associated with clinically significant changes in TSH level,” the researchers wrote in contradiction to the guideline.
And although the researchers were careful to point out that their study was not designed to assess the therapeutic equivalence of levothyroxine generics and brand-name versions, the FDA added yesterday that this CDER-sponsored research “suggests that there may be institutional resistance among some stakeholders that may not be supported by real-world evidence.”
The ATA leadership told Endpoints News via email:
The ATA finds this study reassuring for patients and clinicians. The ATA will include this study in the systematic review they conduct in preparation for their next update of their hypothyroidism guidelines. Meanwhile not all levothyroxine products (all brands and all generics) have been compared with each other in rigorous bioequivalence testing. So it remains reasonable for clinicians to be alert for altered thyroid status in individuals who have their levothyroxine products switched, and consider re-checking a patients thyroid function tests if the clinical situation suggests that the patient may have developed symptoms of either undertreatment or overtreatment of their hypothyroidism.
Editor’s note: Article updated with comment from the ATA.