Levothyroxine Formulation Considerations in Hypothyroidism Management

Antonio Bianco, MD, PhD: One thing I find interesting, especially because there was a recent publication by Juan Pablo Brito [Campana, MBBS] from Mayo Clinic, is how consistent patients should be regarding brands of levothyroxine or different generic medications and even generic vs brand-name medications. I always follow the ATA [American Thyroid Association] recommendation. I tell my patients, pick what you want among the recommended options, but be consistent; stay with your choice. I always tell the patients, speak to a pharmacist, don’t buy medications at different branches of the pharmacy, always go to the same one. Get to know the pharmacist, because sometimes if you’re taking a generic, the source of the generic will change, and that might be a factor in the efficacy of the medication. There are so many variables that we just discussed—time between taking the medication and eating breakfast, other medications, caloric intake. If there’s one variable that we can control, which is the type of levothyroxine you’re taking, I think that’s low-hanging fruit [ie, easy to control]. Focus on selecting one medication and sticking to that one. That concept became solidified for me when I was practicing in Miami, which is a hub for Latino and Hispanic individuals, so many of my patients live a few months in different Latin American countries and a few months in Miami, and I would see their TSH [thyrotropin levels] fluctuate a lot. I would ask them “Where are you getting your levothyroxine?” And they might say, “Well, doctor, every time I’m in a different country, I get different sources of levothyroxine.” From practical experience, I know that makes a difference. There are multiple variables that you can’t control, but this is one - that you can. Dr Hennessey, how do you see it?

James Hennessey, MD, FACP: I agree with you wholeheartedly on that, and I enjoy your insight about the folks down in Miami moving back and forth across borders and getting refills where it’s cheaper…then coming back to the United States and being prescribed yet another brand and having to buy that. When it comes to levothyroxine preparations, I tend to speak not in brand names, but instead I consider each preparation to be a unique formulation. It’s hard for me not to think of each one of these preparations as being unique.

Antonio Bianco, MD, PhD: I think you’re right. Absolutely. Getting back to Dr Brito Campana’s study, what Juan Pablo’s work showed is that exchanging different generic forms is not going to make a big difference in TSH levels, but if you look at the data of most of the patients surveyed, they were taking a low dose of levothyroxine. They were only prescribed up to 50 mcg per day.

James Hennessey, MD, FACP: —56.3%. Or 50 mcg per day.

Antonio Bianco, MD, PhD: That tells me those patients may still have some thyroid reserve, which would tend to buffer major fluctuations in TSH.

James Hennessey, MD, FACP: That’s correct. They looked at generic levothyroxine files from insurance databases in 1000 patients. As is typical, the patients are a little bit older, they’re about 59 years old, and most of them are women, 73%. The unique thing about the 3generics that were used in this analysis was that approximately 82% of the patients being followed were on the same sourced preparation—generic A, generic B, or generic C—and about 17% or 18% were switched among the top 3 generics used. It turns out that the 3 generics being assessed were all rated as AB1, and in FDA parlance, that means that the company showed a certain levothyroxine preparation as its reference and then compared itself to that reference. The 2 other generic companies also compared themselves to that reference. So, all 3 of these drugs were AB1 rated as interchangeable. Because the reference drug was not selling like hotcakes, they also decided to go into the generic market. Therefore, all 3 of those drugs are available as generics and that’s why Juan Pablo picked from those 3—because they had the 3 biggest numbers. All 3 are methyl cellulose-based tablets. They all have similar excipients and bioavailability characteristics. If I were to choose which group of generics to study, to show that there’s no difference among them, I would choose generics with similar recipients. That’s how the study turned out, and it was very interesting.

Antonio Bianco, MD, PhD: I see.

James Hennessey, MD, FACP: The results are somewhat limited, although Juan Pablo doesn’t agree with me, because it was quite clear that results were compiled among those who were compared by propensity score matching. It’s a magically done study.

Antonio Bianco, MD, PhD: Sure. Absolutely.

James Hennessey, MD, FACP: But ultimately, they were not able to demonstrate that there were big differences.

Transcript edited for clarity