Over the course of the last few decades, the FDA has chipped away at removing unapproved prescription drug products from the market. In most cases, the drugs have been marketed for a long time, sometimes referred to as so-called “grandfathered drugs.” However, the FDA’s goal has been to bring all products under the regulatory umbrella of FDA approval and now has come the time for unapproved thyroid products to be removed from the marketplace. The FDA notice of the enforcement action (here) for this class of medication (which is an animal-derived thyroid medication sometimes called desiccated thyroid extract or DTE) notes that there will be a one year time period during which patients should have sufficient time to switch to a synthetic form of the drugs in consultation with their physicians. Thyroid medications have historically been described as narrow therapeutic range drugs and, as stated in the press release from the FDA, “Generally, thyroid hormone replacement medications need to be dosed very carefully. There is only a small difference between a dose that is too low and will not work well and a dose that is too high, which can cause side effects. This means a doctor needs to monitor a patient’s thyroid hormone levels closely and adjust their medication dose precisely to keep their levels in the right range.”

The FDA’s concern regarding approved thyroid products was raised in 2007 when the Agency “issued letters to all new drug application (NDA) and abbreviated new drug application (ANDA) holders requiring that they change the specifications for their products so that all levothyroxine sodium products approved for use in humans will meet a 95% to 105% potency specification throughout their labeled shelf-lives. This action was part of the agency’s ongoing efforts to address concerns about the variability in the stability profile of FDA approved levothyroxine sodium products and is consistent with FDA’s previous regulatory actions intended to ensure that levothyroxine sodium drug products maintain their quality throughout their shelf lives.”

Due to the fact that the desiccated form of the product has not been reviewed by the FDA for safety or efficacy, the FDA’s current enforcement action expresses concerns that:

  • “Tablets made from the same manufacturing batches may not always provide the same thyroid hormone levels. Inconsistent doses can have serious consequences for patients. Too much medication can cause unwanted effects, and too little could not be effective.
  • Thyroid medications derived from animal thyroid glands have an increased risk of certain impurities due to the source – animal thyroid tissue – or the way it is manufactured. These issues can lead to infections and other health concerns.”

The FDA has sent letters to the manufacturers of desiccated thyroid products (here) that identify the FDA’s concerns and give the background as to why the Agency is taking this action.

The FDA believes that allowing for a transition period of twelve months for practitioners to switch patients to a synthetic thyroid product is sufficient; however, making the switch and finding the specific and correct dose for each patient will be a process that has the potential to raise concerns in patients. Remember that there are currently over fifteen different strengths of levothyroxine oral dosage forms being marketed. The product is dosed in micrograms and the difference in many doses is very minute. If the twelve months are not sufficient for practitioners and patients to make the switch successfully, perhaps the FDA will lengthen the enforcement discretion period. We will have to wait and see.