Liquid Levothyroxine Better for Hypothyroid Patients

Tablets found to be less effective treatment

tirosint, levothyroxine, thyroid treatment, hypothyroidism drugs
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At the 2017 meeting of the American Thyroid Association, a number of researchers reported on new studies that showed that liquid forms of levothyroxine are more effective than tablets in treating many groups of patients.

Levothyroxine is a synthetic drug form of thyroxine (T4), a key hormone produced by the thyroid. Levothyroxine is the primary treatment for hypothyroidism, an underactive thyroid that most commonly results from surgical removal of the thyroid, radioactive ablation of the gland, and destruction of the gland as a result of the autoimmune disease Hashimoto’s thyroiditis.

Generic levothyroxine, and commonly-known brand names such as Synthroid and Levoxyl, are tablet forms of this thyroid hormone replacement drug. The tablet form of levothyroxine is the predominant way this drug is taken.

For several years, a liquid, softgel capsule form of levothyroxine has been available in the United States under the brand name Tirosint. The Tirosint brand of levothyroxine was designed primarily as a hypoallergenic, specialized form of levothyroxine for people who have digestive or intestinal problems, difficulties with absorption of thyroid medication, or allergies to the fillers and binders in the tablet formulations of levothyroxine drugs.

In February of 2017, the FDA approved a liquid levothyroxine, Tirosint-SOL. Liquid levothyroxine has been available in Italy since 2012. The liquid levothyroxine was intended as an alternative for patients who cannot swallow, who are fed by tube, and for children with hypothyroidism. Tirosint-SOL is expected to be available throught the U.S. market by 2018.

Liquid Levothyroxine vs. Tablets

In one study, Italian researchers demonstrated that liquid forms of levothyroxine result in better normalization of thyroid levels compared to tablets. They evaluated a group of patients taking levothyroxine tablets, who, despite dosage increases, did not have thyroid stimulating hormone (TSH) and free T4 levels within the reference range.

The researchers switched the patients to the same doses of liquid or softgel levothyroxine and remeasured their thyroid levels. They found that 85 percent of the patients studied showed a significant improvement in both their TSH levels and their free T4 levels. Several weeks after starting the liquid forms of levothyroxine, the hypothyroid patients were able to reach thyroid levels within the targeted reference ranges.

The researchers concluded that the liquid forms of levothyroxine have a more favorable outcome when compared to tablet formulation in some patients.

After Thyroidectomy, Softgel Capsules More Effective

In another study, researchers compared the effectiveness of levothyroxine tablets and softgels in patients who had a total thyroidectomy for a multinodular goiter. These patients did not have any malabsorption issues.

Around half the patients studied were given tablets, and the other half received the softgel capsules at the same disease, starting immediately after the thyroid surgery. The patients’ TSH, free thyroxine (FT4), and free triiodothyronine (FT3) levels were evaluated after 6 weeks and then after 12 weeks.

At both 6 and 12 weeks, the patients taking the softgel capsules had significantly lower TSH levels. At both measurement points, the number of patients who had elevated TSH levels above 3.5 mcU/ml—deemed hypothyroid for this study—was significantly higher in the patients receiving tablets. The researchers concluded that even in patients who had no malabsorption or digestive issues, levothyroxine softgel capsules were more effective.

Better TSH Control TSH After Cancer

Another Italian study looked at patients with differentiated thyroid cancer (DTC) taking levothyroxine. According to the American Thyroid Association, these patients should main a TSH level between 0.1 and 0.5 mU/L—below the lower end of the reference range—to help prevent recurrence of thyroid cancer. Because this is a relatively narrow window, it’s important that levothyroxine treatment be consistent in maintaining the TSH level.

The researchers compared the variability of the TSH level in patients treated with liquid levothyroxine, versus tablets. Half the patients received liquid levothyroxine, and half received a tablet, and all had the same thyroid hormone replacement dosage. Several measurements of TSH levels were done.

The researchers saw a significant increase in TSH levels in the patients taking tablets, compared to those taking liquid levothyroxine. Specifically, almost 16 percent of the patients on tablets did not reach the target TSH range, compared to only 4% of those on the liquid levothyroxine. The researchers concluded that the use of LT4 levothyroxine compared to tablets resulted in a significantly higher number of the cancer patients maintaining TSH values the targeted range to lower their risk of cancer recurrence.

About Liquid Levothyroxine

As noted, in the U.S., commercially manufactured liquid levothyroxine is available in Tirosint brand softgel capsules, and in Tirosint-SOL liquid. Tirosint does not contain sugars, dyes, alcohol, wheat starch (gluten), lactose, acacia, or any other additives or fillers that are commonly used to make levothyroxine tablets. The only ingredients in the capsules are levothyroxine, gelatin, glycerin, and water, which are not likely to interfere with absorption or cause allergies. The Tirosint-SOL contains only levothyroxine.

Tirosint has been reserved primarily for patients who have conditions like Crohn’s disease or irritable bowel syndrome that are known to affect digestion or absorption. Because it is hypoallergenic, it is also used by patients with known allergies to fillers or ingredients used in the manufacture of brand name and generic levothyroxine tablets. 

Some added benefits of Tirosint liquid formulations: food, calcium, iron, coffee, and milk do not appear to interfere with absorption of liquid levothyroxine, as they do with tablets.  

Because of its status as a specialty drug for a limited audience, and because Tirosint is significantly more expensive than other brands of levothyroxine or generic tablets, it has to date not been widely used for hypothyroidism treatment in the United States.

A Word From Verywell

The research findings suggest that many patients—not just those with malabsorption or allergies—could potentially benefit from switching away from tablet forms of levothyroxine to the liquid forms of levothyroxine. Another research study published in the journal RD Diet found that among 1,000 patients taking levothyroxine, 15 percent had allergies to the fillers and additives found in levothyroxine tablets.

There are some challenges to making a switch from a tablet levothyroxine to Tirosint softgel capsules or Tirosint-SOL liquid, however:

  • Your doctor may not be aware of Tirosint capsules or Tirosint-SOL liquid as options.
  • Your insurance, HMO, or other health coverage may not be willing to pay for or reimburse for Tirosint. In this case, you may need your health care provider to justify a “dispense as written” or “no substitution/no generic” prescription.
  • If you have to pay out-of-pocket, the cost differential—which can be as much as $50 to $100 or more per month—may make the switch prohibitive for you financially.

If, however, you are finding it challenging to reach your targeted or optimal thyroid test levels and resolve your continuing symptoms of hypothyroidism, you may want to have a discussion with your healthcare provider regarding whether a switch in your treatment is recommended.

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Article Sources
  • Benvanga, S. et al. “L-Thyroxine in an Oral Liquid or Softgel Formulation Ensures More Normal Serum Level of Free T4.” Thyroid. October 2017, 27(S1): A-166-A-188. 
  • Fallahi, P et. al. “Oral L-Thyroxine in Gel Capsule Versus the Tablet Formulation in Patients Submitted to Total Thyroidectomy.” Thyroid. October 2017, 27(S1): A-166-A-188. 
  • McMillan M, Rotenberg K, et al. Cormorbidities, Concomitant medications, and diet as factors affecting levothyroxine therapy: results of The CONTROL surveillance project. Drugs RD. 2015. December 21. 
  • Pirola, I. et. al.  “TSH Variability in Patients Affected by Differentiated Thyroid Cancer Treated with Levothyroxine Liquid Solution or Tablet.” Thyroid. October 2017, 27(S1): A-166-A-188. 
  • Sevilla Alsina, ME et. al. “An Alternative Approach in the Management of Hypothyroidism After Failure of Oral Levothyroxine.” Thyroid. October 2017, 27(S1): A-166-A-188.