Considerations for Generic-to-Generic Levothyroxine Switching

Abstract

To the Editor I am thankful to Brito et al 1 for considering the clinical effect of switching US Food and Drug Administrationapproved generic levothyroxine products in their recent comparative effectiveness research study. The authors included adults who filled generic levothyroxine preparations from any of the 3 most common manufacturers: Mylan, Sandoz, and Lannett. All 3 of these preparations are AB1 rated, as they meet bioequivalence requirements to an AB1-rated reference drug. The Mylan and Sandoz products were rated to Lannett's Unithroid. However, Mylan was not compared with the Sandoz product, so they are not technically therapeutically equivalent. Pharmacists may view all AB1-rated products as equivalent. All 3 products have a common microcrystalline cellulose excipient, likely resulting in similar dissolution characteristics and bioavailability. The reader should not extend this apparent clinical interchangeability beyond these 3 similar generics, as the authors acknowledged.The effect of residual endogenous thyroid function on these outcomes is a shared concern. 1 Less than 2% of patients had athyreosis. This would be most applicable to the nearly onethird of patients who likely had no underlying hypothyroidism 2 and were included in the nearly 60% ingesting no more than 50 μg and the 87% with a daily dosage less than 100 μg. I believe this residual function results in a buffering effect on clinical outcomes, making it difficult to detect differences in bioavailability.On the basis of clinical experiences following substitution of levothyroxine products during manufacturing disruptions 3 and introduction of reformulated (pharmacokinetically equivalent) products, 4 the European Thyroid Association 5 recommends caution, counseling, and follow-up testing in patients who have switched from 1 product to another.I agree that the results of the study by Brito et al 1 are not applicable to switching from brand-name to generic products. The aforementioned limitations should have softened the conclusion that switching generic levothyroxine products is unlikely to have substantial implications for treatment effects. When patients report that their dispensed LT4 tablets look different, I will be moderately reassured if they are on low doses of the products addressed by Brito et al. I will still offer a worried patient a thyrotropin check and follow-up visit in 6 weeks to allay their anxiety, maintaining the patientphysician relationship.