Levothyroxine, a synthetic form of the thyroid hormone T4, is the primary treatment for the underactive thyroid condition known as hypothyroidism. It's currently estimated that as many as 13 million Americans take thyroid hormone replacement medication for hypothyroidism. At present, there are eight different brand name and generic levothyroxine products being manufactured in the U.S. The brand names include Synthroid, Levoxyl, Levothroid and Unithroid.
For insurance companies and HMOs, generic levothyroxine is considered equivalent to the brand names. And because there is a substantial cost differential between generic levothyroxine and many of the brand name products, insurers, HMOs and patients have been turning to generic levothyroxine.
According to the professional organizations, however, "generic levothyroxine preparations are frequently dispensed as equivalent to branded preparations, while not necessarily being shown to be therapeutically equivalent...FDA bioequivalence standards for levothyroxine product comparisons and directions to pharmacists for product substitution may result in some patients no longer receiving the proper amount of levothyroxine."
Representatives of AACE, ATA and the Endocrine Society are sharing their concerns at a joint meeting of the FDA Metabolic Drugs Advisory Committee and the Advisory Committee for Pharmaceutical Science on October 4, 2006. The consortium has three main concerns.
1. They believe that the method used by the FDA to compare the different levothyroxine products -- and which has identified them as equivalent -- is not sensitive enough to be accurateThe consortium claims that the different levothyroxine formulations are being substituted for one another "with little regard to whether or not they are equivalent, even by FDA, as opposed to professional society, standards." They report that:
2. The current policy generates additional cost and inconvenience, because patients require additional blood tests and dose adjustments after switching to generic levothyroxine preparations
3. The FDA is not using the serum Thyroid Stimulating Hormone (TSH) test to compare bioequivalence of levothyroxine preparations, and the consortium believes the TSH test to be "the most reliable indicator of thyroid hormone action"
...of the 56 potential switches between products, only 14 (25%) of these potential changes have been directly compared by bioequivalence testing. Yet, the FDA has directed pharmaceutical companies to delete the "black box" warning indicating that dose adjustments may be required after switching patients from one preparation to anotherleaving patients and physicians unaware of whether or not thyroid hormone levels have been affected by the change.
What Does This All Mean?The basic issue is that levothyroxine does vary in terms of potency from manufacturer to manufacturer.
As a patient, if you use a particular brand of levothyroxine, most batches will have a consistent potency -- barring any unusual manufacturing irregularities. So if you are on a brand name levothyroxine, and you get the same brand with each prescription refill, you should not experience much potency variation, if any.
Each manufacturer's generic levothyroxine product is also considered consistent in potency. However, when you are prescribed a generic product, your doctor is not able to specify which manufacturer's generic product you will get. And your pharmacist cannot guarantee that you'll get your generic levothyroxine from a particular manufacturer. Patients who take generic levothyroxine can, with each prescription refill, receive product from any one of the various manufacturers of generic levothyroxine. Since generic levothyroxine drugs do not have consistent potency from one manufacturer to the next, this introduces the possibility that with each new refill of medication, you will get a batch from a different manufacturer...one that is too potent, or not potent enough -- effectively delivering too much or not enough levothyroxine.
If you get too much levothyroxine than you need, you can experience debilitating and sometimes dangerous symptoms of hyperthyroidism, for example insomnia, anxiety, high heart rate, high blood pressure, diarrhea, hair loss, and an increased risk of osteoporosis. If you get too little levothyroxine, your hypothyroidism is undertreated, leaving you with symptoms that may include exhaustion, weight gain, depression, infertility, and an increased risk of heart disease, among others.