The U.S. Food and Drug Administration is tightening the potency specifications for levothyroxine sodium, used to treat underactive thyroid glands and other thyroid conditions, to ensure the drug retains its potency over its entire shelf life. This action is being taken in response to concerns that the potency of the drug may deteriorate prior to its expiration date.
The change will help improve the quality of the product so that consumers receive the level of medication needed to treat their thyroid disorders. Levothyroxine sodium products are used by over 13 million patients.
FDA is mandating that levothyroxine sodium drug products tighten their potency specifications to meet a 95 percent to 105 percent potency specification until their expiration date. The shelf life is the length of time a drug can be stored before it degrades to unacceptable levels. The 95 percent lower potency 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. Currently, these products are allowed a potency range of 90 to 110 percent.
The action is consistent with the recommendations of a joint FDA advisory committee and follows concerns expressed about levothyroxine sodium products by health care professionals and patients. Manufacturers and marketers have two years to comply with the revised specification.
A healthy, functioning thyroid gland is critical to regulating a person’s overall metabolic function, which consequently impacts a host of other bodily functions. “These medicines are vital to people taking thyroid replacement or suppression therapies,” said Janet Woodcock, M.D., deputy commissioner and chief medical officer and acting director of FDA’s Center for Drug Evaluation and Research. “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.”
Consumers can also help maintain the potency of their medications by storing medications in a dry place at room temperature and avoiding humid, hot environments such as bathrooms, which speed deterioration.
Over the past decade, the FDA has spent considerable resources to ensure that levothyroxine sodium products are safe and effective. The FDA requested and received stability data from manufacturers of all the approved, marketed levothyroxine sodium drug products manufactured between July 2003 and June 2005, and examined the stability profile of each drug.
The data revealed a trend toward a loss of potency, with some preparations showing potency approaching 90 percent of labeled potency by the expiration date. Although all approved levothyroxine sodium products fall within the current potency specification of 90 percent to 110 percent, the stability data showed that some products rapidly degrade over their labeled shelf life. Some strengths or package types, such as blister packs, degrade more rapidly than others, resulting in varying expiration dates within product lines. In addition, there is variability in expiration dating periods between products from different manufacturers. Some levothyroxine sodium tablets remain very stable, losing less than 5 percent of labeled potency within 24 months, while other products lost approximately 10 percent of labeled potency in 9 months. 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.
Levothyroxine sodium products have been marketed for decades in the United States. This class of drugs is used to treat hypothyroidism, as a thyroid replacement therapy, to suppress the growth of benign goiters and thyroid cancer, and as an adjunct to surgery and radioiodine therapy designed to manage some types of thyroid tumors.