Bioequivalence of generic Synthroid questioned

OB/GYN News, Oct 1, 2004 by Elizabeth Mechcatie

A recently approved generic formulation of levothyroxine "is significantly more potent" than Synthroid, and could lead to serious side effects if a patient were switched from one to the other, two clinical endocrinology organizations have warned.

Bioequivalence data used as the basis of the recent approval of a generic version of levothyroxine indicate that the generic--manufactured by Sandoz and approved in June--"may be as much as one-eighth more potent" than Synthroid, the American Thyroid Association (ATA) and the American Association of Clinical Endocrinologists (AACE) said in a statement.

This information "confirms our concern that current FDA standards defining the equivalence of levothyroxine products are too lax," and "switching between two products could compromise the effectiveness of treatment," resulting in serious side effects, AACE president Dr. Carlos Hamilton said in the statement.

Levothyroxine has a narrow toxic-to-therapeutic ratio, so "even minor or inadequate dosing" can result in problems for the patient, the statement said. Synthroid, manufactured by Abbott Laboratories, has been the most widely used brand of levothyroxine.

The ATA and AACE recommend that physicians "encourage" their patients on levothyroxine to stay on the same preparation, if possible, although pharmacies may switch products. If the preparation has to be switched, patients will need to have a thyroid-stimulating hormone blood test 4-6 weeks afterward to determine if the dosage needs to be adjusted.

The FDA is evaluating the ATA/AACE statement, and did not have a response at press time.

Michael Roth, who is executive director of communications at Novartis, told this newspaper that the company stands by approval of the Sandoz product, which is "therapeutically bioequivalent to both Synthroid and Levoxyl." (Levoxyl was approved in 2001.) The company has "conducted significant testing of our product to ensure stability and validated that our product does, indeed, match that of the branded counterparts," he said. Sandoz is the generic business unit of Novartis.

BY ELIZABETH MECHCATIE

Senior Writer