Potency specifications tightened for levothyroxine.

The Food and Drug Administration has tightened the potency specifications required for levothyroxine sodium products, mandating that they cannot lose more than 5% of their baseline potency by the time they reach their expiration date.

The FDA announced that levothyroxine products will have to meet a 95%-105% potency specification until their expiration date. Until now, the allowed potency range has been 90%-110%. At a meeting last year, two FDA advisory panels agreed that the looser standard raised clinically significant concerns and should be tightened to the 95%-105% range. Manufacturers and marketers have 2 years to comply with the new specification, according to the FDA.

The tighter specification "will ensure the drugs do not degrade by more than 5 percent of the labeled claim before their expiration date, and the 105 percent upper specification is appropriate to address occasional analytical testing variability," the FDA statement said. "By tightening the potency specification and limiting the amount that products can degrade throughout their shelf life, FDA is reducing the variability in the stability profiles between products that could have clinical consequences in achieving target thyroid levels, especially for the most vulnerable patients, such as those with thyroid cancer."

The FDA is also recommending that patients store levothyroxine in a dry location at room temperature. The agency notes that hot, humid environments such as bathrooms can increase the drug's deterioration rate.

Dr. Janet Woodcock, acting director of FDA's Center for Drug Evaluation and Research, and deputy commissioner and chief medical officer, added that tightening the potency specifications "will ensure that the most vulnerable patients taking thyroid medication will receive the appropriate level of drug therapy needed for their condition."

The three major endocrine professional societies welcomed the tighter potency standards for levothyroxine products, but reiterated that the larger issue of bioequivalence between preparations remains the more clinically significant issue.

A statement released by the Endocrine Society after the FDA announcement was made says that the FDA's recent efforts are "a reasonable step to ensuring the safety of patients taking L-T4 [levothyroxine sodium]," but urged the agency to do more.

The statement noted that since 2005, the Endocrine Society, the American Association of Clinical Endocrinologists, and the American Thyroid Association have been asking the FDA to reconsider its current system for determining bioequivalence of levothyroxine products. "Tightening of potency specifications will alleviate some, but not all, of the measured variability among L-T4 products, and it does nothing to address the flawed method by which FDA determines bioequivalence of the drugs."

Instead of taking a pharmacodynamic approach, the FDA's method of determining bioequivalence is based on pharmacokinetics, and entails measuring serum thyroxine levels after an oral dose of levothyroxine.

To avoid the problems involved in switching products, the societies continue to recommend that patients stay on the same levothyroxine brand, and that physicians request "no substitutions" when writing prescriptions.

If a pharmacist does substitute with a generic, he said the patients need to have the levothyroxine dose retitrated and should have their free [T.sub.4] and TSH levels checked after 6 weeks on the new preparation, at which time the dose should be adjusted accordingly.

An FDA spokesperson said that the "FDA believes that requiring all marketed levothyroxine sodium products to adhere to a tighter potency specification will minimize any clinical differences that may result from switching between different levothyroxine sodium products or refilling a prescription with the same prescribed product."

BY ELIZABETH MECHCATIE

Senior Writer