Is Synthroid Better Than Generic Levothyroxine?

Generic drugs help reduce treatment costs while generally delivering equal (non-inferior) results. However, there is debate as to whether generic levothyroxine is equally effective as the brand name version, Synthroid, in treating hypothyroidism.

Some studies suggest that generic levothyroxine, the synthetic form of the thyroid hormone thyroxine (T4), is non-inferior to Synthroid in treating mild hypothyroidism. Others have found that switching from Synthroid to a generic may make it harder to maintain tight control of your thyroid hormone levels.

This article will tell you what you need to know about generic levothyroxine products, including their ingredients, safety, costs, and how they compare to Synthroid.

How Ingredients Differ

Levothyroxine sodium is the second-most prescribed drug in the United States, with approximately 25 million people using either Synthroid or generic levothyroxine to manage their hypothyroidism (low thyroid function).

In addition to Synthroid, there are seven generic versions licensed in the U.S.

Generic drugs in the United States are regulated by the Food and Drug Administration (FDA) to ensure that the active ingredients are not only the same but that a generic is also bioequivalent (meaning delivering the same intended effect) to the brand-name drug.

These standards must be documented and approved by the FDA before a generic manufacturer can produce and sell the drug.

As a means of illustration, here is how Synthroid matches up to two of the leading generic levothyroxine products, Levo-T and Levoxyl.

Comparative Safety of Synthroid and Generics

Generic levothyroxine products licensed by the FDA are just as safe as Synthroid. There is no evidence of one being "more safe" or "less safe" than another.

The safety is ensured in part by a certification process overseen by an independent authority called the United States Pharmacopeia (USP). The USP certifies that a drug contains the stated amount of ingredients listed on the product label and that no impurities were found.

All generic levothyroxine products in the United States are independently certified by the USP.

While it is possible to be sensitive to certain inactive ingredients in levothyroxine, like lactose or color additives, the amounts are generally so low as to pose few health risks.

Risk of Heart Disease?

Despite its reported safety, some studies in the past had suggested that generic levothyroxine was linked to an increased risk of cardiovascular disease when compared to Synthroid.

While people with hypothyroidism are generally at a higher risk of cardiovascular diseases, including heart attack, congestive heart failure, atrial fibrillation, and stroke, managing thyroid levels with levothyroxine can greatly reduce the risk.

As such, if the early findings were correct, it would suggest that generic levothyroxine works "less well" in managing thyroid disease.

These concerns were largely laid to rest in 2019 based on research published in the Mayo Clinic Proceedings. According to the analysis of over 87,000 people on either Synthroid or generic levothyroxine, there were no differences in the rate of heart attack, heart failure, atrial fibrillation, or stroke in either group.

Even so, ongoing concerns about the safety and efficacy of generic levothyroxine have altered the prescribing practices of some healthcare providers.

According to the American Thyroid Association, primary care providers are more likely to prescribe generic levothyroxine, while specialists like endocrinologists who treat diseases like hypothyroidism are more likely to prescribe Synthroid.

Cost Difference With Generic Levothyroxine

Generic drugs generally, but not always, cost less than their brand-name counterparts. The longer that a generic drug is on the market, the smaller the cost difference will be (due largely to the decreasing price of the brand-name drug).

With Synthroid, the issue is slightly different. While the drug has been around since 1955, it was only formally approved by the FDA as a "new drug" in 2002. Thereafter, the first generic was awarded FDA approval only two years later, in 2004.

As of 2023, the average retail price of Synthroid 50 mg hovers at around $150 for a 90-day (three-month) supply. In contrast, the average retail price of generic levothyroxine 50 mg is closer to $45 for a 90-day supply.

Effectiveness of Generic Levothyroxine

Prior to the acquisition of Synthroid by AbbVie (then Abbott Pharmaceuticals) in 2001, the FDA received numerous complaints from consumers and medical associations citing inconsistencies in drug quality by the original manufacturer, Knoll Pharmaceuticals.

With the rapid approval of several levothyroxine generics in 2004, these concerns spilled over with organizations like the American Association of Clinical Endocrinologists (AACE) and the American Thyroid Association (ATA) arguing that the newer generics were not bioequivalent to Synthroid.

These authorities argued that FDA policy allows potency ranges of generical to vary by 5%, meaning that the potency can fall anywhere from 95% and 105% of the brand-name product. With levothyroxine, either extreme can be problematic—making it harder to stabilize thyroid function if patients are underdosed with one generic and overdosed with another.

The problem, the AACE and ATA state, becomes even greater if a patient switches between generics or between a generic and Synthroid.

Recent studies have largely allayed some of these fears:

• Differences in efficacy: A 2020 study published in the Journal of the American Medical Association Open Network found that generic levothyroxine is as effective as Synthroid for the initial treatment of mild hypothyroidism. The analysis involved 17,598 adults prescribed levothyroxine from 2008 to 2017.
• Switching between generics: A 2022 study in the Journal of the American Medical Association Internal Medicine found that switching from one generic levothyroxine product to another does not significantly affect thyroid hormone levels in people with hypothyroidism. A total of 15,829 adults were involved in this research.

Can I Switch From Synthroid?

Not all of the concerns about generic levothyroxine have been allayed. For example, if you are taking Synthroid and thinking about switching to save costs, there is evidence that doing so may not be the best idea.

A 2019 study published in Advances in Therapy compared 9,925 adults who consistently used Synthroid to 9,925 adults who switched from Synthroid to a generic. What the researchers found was that people who switched were 15% more likely to have their thyroid hormones fall out of the "normal" range than those who stuck with Synthroid.

While this may suggest that Synthroid is somehow "better" than the generics, there are other possible explanations for the disparity. Among them, studies have shown that the very practice of switching is linked to poor drug adherence. By contrast, sticking with the same drug—irrespective of the drug type—is associated with better adherence and better outcomes.

What You Can Do

Despite some continuing debate over the efficacy of generic levothyroxine vs. Synthroid, most experts agree that the main focus should be placed on taking your thyroid medications consistently and correctly.

To do this:

• Take levothyroxine on an empty stomach 30 to 60 minutes before breakfast to avoid erratic absorption.
• Take levothyroxine at the same time in the morning, keeping to a consistent routine.
• Never run out of drugs. Set a reminder on your cell phone so that you know when to renew your prescription or request a new prescription
• Ask your pharmacist to order the same drug every month. Your healthcare provider can write "DAW" (dispense as written) on the prescription to ensure the same brand is prescribed.
• If you experience an upset stomach or other digestive side effects that make it hard to adhere to treatment, ask about a softgel form of levothyroxine called Tirosint that is more tolerable for people with sensitive stomachs.
  
• If you are unable to maintain normal thyroid hormone levels despite perfect adherence—ask your provider if you should also take Cytomel (liothyronine), a synthetic version of the thyroid hormone triiodothyronine (T3)—to bolster your response.
  

Summary

Despite concerns that generic levothyroxine may not be as effective as the brand-name drug (Synthroid), a growing body of research has shown that both are equally effective when first starting treatment of mild hypothyroidism.

While switching between generics may also be OK, the American Thyroid Association recommends staying with one drug rather than switching from one to the next. Whatever form of levothyroxine you use, take it daily as prescribed to ensure the best results.