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| FOR IMMEDIATE RELEASE Oct. 15, 2006 |
Contact: Jennifer Reising at jreising@reisingcommunications.com |
American Thyroid Association Speaks Out on FDA Methods for Assessing Bioequivalence of Thyroid Hormone
Recent testimony to FDA and physician survey on significant adverse events in patients are focus of Public Health Symposium at Annual Meeting
(PHOENIX, Oct. 15, 2006)—Improving the outcomes of the 13 million patients who are treated with the thyroid hormone levothyroxine (L-T4) was the focus of a presentation at the “Public Health and the Thyroid” symposia taking place today at the American Thyroid Association’s (ATA) 77th Annual Meeting. Recently acquired data quantified the potential harmful impact of the Food and Drug Administration’s (FDA) 1994 ruling that all levothyroxine preparations are therapeutically equivalent. The survey was spearheaded by the ATA and was completed with the participation of ATA members, and sister society members of The Endocrine Society and the American Association of Clinical Endocrinologists as well as being widely distributed through the medical community.
Levothyroxine is a synthetic thyroid hormone used as a replacement when the thyroid gland does not produce enough thyroid hormone and is underactive — a condition called hypothyroidism. The drug can improve symptoms of thyroid deficiency, such as slow speech, lack of energy, weight gain, hair loss, cold sensitivity, and thick, dry skin. Levothyroxine can also be used to treat goiter, an enlarged thyroid gland, and thyroid cancer.
In 1997, the FDA revised the drug approval process for levothyroxine after receiving 58 adverse drug event reports over a period of seven years. As part of this change in the approval process, the FDA issued standards for thyroxine bioequivalence, deeming that levothyroxine preparations that meet these standards have the same clinical effect and safety profile as the reference product to which they are compared. This then allows pharmacists to switch to generic versions of levothyroxine for another — not necessarily with the knowledge of the patient or the physician. Of concern is that levothyroxine is a drug known to have a narrow toxic-to-therapeutic ratio, with the potential for significant clinical consequences of even minor excessive or inadequate dosing.
If a patient gets more levothyroxine than needed, potential side effects include insomnia, anxiety, increased heart rate, atrial fibrillation, high blood pressure, diarrhea, hair loss, and an increased risk of osteoporosis. If too little levothyroxine is provided, hypothyroidism results, potentially leaving patients with symptoms like fatigue, weight gain, depression, infertility, and an increased risk of heart disease.
Representatives of the ATA, American Association of Clinical Endocrinologists, and The Endocrine Society have been voicing their concerns to the FDA for more than two years, most recently at a joint meeting of the FDA Endocrinologic and Metabolic Drugs Advisory Committee and the Advisory Committee for Pharmaceutical Science on Oct. 4, 2006. The primary concern, reiterated during the public comment period at this meeting, is that the method used by the FDA to compare the different levothyroxine products — and which has identified them as equivalent — is not sensitive enough to detect clinically important differences in levothyroxine preparations.
The societies also emphasized that that the FDA policy generates additional cost and inconvenience because patients are encouraged to return for additional blood tests and clinical assessment to determine the need for potential dose adjustments after being switched to a different levothyroxine preparation. Moreover, the thyroid experts pointed out that the FDA is not using the gold standard blood test used clinically to assess and adjust levothyroxine dose in patients, called the thyroid-stimulating hormone (TSH) test.
James Hennessey, MD, of Providence, R.I., representing the ATA, presented data to the FDA on October 4 that had been collected by the three endocrine societies from clinical practitioners who reported that changes in levothyroxine preparation in a small fraction of patients were associated with significant adverse events. Dr. Hennessey also reported this survey data to meeting attendees at the ATA’s “Public Health and the Thyroid” symposium on October 15. Streaming video of his presentation to the ATA will be available online in January 2007.
Of the 1,421 physicians who responded to the survey, 210 levothyroxine prescribers suspected an adverse event and completed additional information. Of these responders, 160 provided information indicating that switching of levothyroxine preparations had occurred. Eighty-eight percent reported that their patients were switched without their knowledge. Of these patients who were switched, 31% experienced a significant adverse event, such as an urgent clinic visit, emergency room visit, hospitalization, and missed work.
Specific examples provided by physicians include:
- Failure to achieve target TSH levels in a thyroid cancer patient, an important goal to prevent tumor recurrence, due to the sub-potency of a substituted thyroxine preparation;
- Reoccurrence of heart disease symptoms, which abated after switching back to the original name brand preparation;
- Previously stable hypothyroidism becoming unstable on a new preparation; and
- Development of atrial fibrillation in a thyroid cancer patient due to the super-potency of a substituted preparation.
“In 1997, the FDA changed the process for approving levothyroxine preparations after receiving 58 adverse drug event reports over a seven-year period on the potency of levothyroxine products,” noted Dr. Hennessey. “In contrast, in 2006, in a period of a few weeks, we have through our survey, received 210 reports of suspected adverse events resulting from both super- and sub-potency. The majority of these reports were associated with a switching of levothyroxine preparations. Somehow, we’ve yet to get the FDA’s full attention to this matter.”
For more information on thyroid hormone bioequivalence, visit the ATA web site at www.thyroid.org.
The newest research in mechanisms, diagnosis, and clinical management of thyroid disease as well as other important health care issues were featured at the ATA Annual Meeting, Oct. 11–15, 2006, at the Sheraton Wild Horse Pass Resort & Spa in Phoenix. The meeting has brought together thyroid experts from the United States and around the world.
The American Thyroid Association is a nonprofit professional medical society composed of physicians and scientists dedicated to enhancing the understanding of thyroid physiology and pathophysiology, improving diagnosis and treatment of thyroid diseases, and promoting the education of physicians, patients, and the public about thyroid disorders. The ATA’s web site, www.thyroid.org, provides professional and patient resources, such as treatment guidelines, thyroid health brochures in English and Spanish, and access to Friends of the ATA, a patient-oriented service providing access to the latest in thyroid health information.
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