Chevy Chase, MD—While substituting one brand of a prescription medication for another is usually safe and effective, substitutions for sodium levothyroxine (L-T4), a medication used for the treatment of thyroid disease, can result in adverse health effects. The body is very sensitive to small alterations in thyroid hormone levels, and L-T4 doses from different manufacturers can deliver significantly varying amounts of the drug resulting in potential clinical problems.

Under current rulings by the U.S. Food and Drug Administration (FDA), doses of L-T4 from certain manufacturers are considered the same as, or bioequivalent to, those from other manufacturers. Due to this ruling, patients can be switched between certain sources of L-T4 without the knowledge of the prescribing physician.

To address this potential risk to patients with thyroid disease, The Endocrine Society has issued a new position statement that outlines a series of recommendations to Congress, the FDA, and physicians.

"Even a slight change in L-T4 dose, such as when a patient is switched from one source to another, can adversely affect cardiac and brain function, among other things," said Dr. Robert M. Carey, president of The Endocrine Society. "These effects are even more pronounced in children, who can also suffer long-term developmental delay."

L-T4 is a synthetic version of thyroxine, a thyroid hormone made naturally in the body. Thyroid hormones regulate important biological functions, including metabolism, the nervous system, and the cardiovascular system. Thyroid hormones are also important for proper growth and development in children, including normal brain development in infants and toddlers.

In order to ensure the safety of patients, the position statement calls for the FDA to reverse its current ruling of bioequivalence among L-T4 products and use a more sensitive and clinically relevant method to determine bioequivalence. The current method calls for an analysis of a snapshot of the level of thyroxine in the blood of normal volunteers after administration of large doses of L-T4.

According to the position statement, this method fails to take into account the measurement of serum concentrations of the pituitary hormone thyroid stimulating hormone (TSH), which is a more sensitive indicator of the body's exposure to thyroid hormone than the direct measure of thyroid hormones in the blood.

"Small changes in TSH levels, even in the absence of measurable changes in blood level of thyroid hormone, have been associated with significant adverse clinical consequences," said Dr. Carey. "Under the FDA's current determination of L-T4 bioequivalence, there is no guarantee that a patient's effectively absorbed dose will remain constant enough to stabilize TSH levels if the patient is switched from product to product."

To safeguard the health of patients, the Society supports the following actions:

• Congress should encourage the FDA   to design and implement a method to determine bioequivalence of L-T4 that   will consider TSH levels over time, the most sensitive and clinically   relevant measure of L-T4 efficacy.
• The FDA should rescind its current   determinations of bioequivalence among L-T4 products and instead announce   that the products have not been shown to be bioequivalent. This will   ensure that patients' prescriptions are not switched without the order of   the prescribing physician.
• The FDA should require patient   warning information in L-T4 products emphasizing the importance of   consulting the prescribing physician if the source of L-T4 is switched.
• Physicians who are not thyroid   specialists must be fully informed of the potential consequences of even   slightly altered doses of L-T4. Therefore, physician-targeted information   in L-T4 products must clearly communicate the potential problems with even   slight alterations in dose and the need to re-evaluate the patient upon   substitution. 

The Endocrine Society's position paper on bioequivalence of sodium levothyroxine is here: http://www.endo-society.org/advocacy/policy/upload/L-T4-Position-Statement-with-member-comments-header.pdf

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Founded in 1916, The Endocrine Society is the world's oldest, largest, and most active organization devoted to research on hormones and the clinical practice of endocrinology. Today, The Endocrine Society's membership consists of over 14,000 scientists, physicians, educators, nurses and students in more than 80 countries. Together, these members represent all basic, applied, and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Md. To learn more about the Society, and the field of endocrinology, visit our web site at www.endo-society.org.