FDA Issues Guidance on Levothyroxine Sodium, a Popular Thyroid Hormone
For decades, Levothyroxine sodium, the most popular thyroid hormone for replacement therapy, had not been required to go through the Food and Drug Administration's approval process. But in 1997, the FDA reclassified all oral levothyroxine products as "new drugs," obligating the manufacturers to meet approved New Drug Applications (NDAs) before August 14, 2001. A history of potency and stability problems with orally administered levothyroxine sodium products resulted in the agency's decision.
Two levothyroxine sodium products, Unithroid and Levoxyl, have recently been approved by the FDA to treat hypothyroidism. And now the FDA is issuing guidance regarding the transition of patients from unapproved to these approved products, and the handling of those products being marketed without an approved application. The FDA will gradually do away with the unapproved products to allow manufacturers of approved products to expand to meet demand and to give patients and health care providers enough time for a clean transition.
Two of the most common formulations that are being phased out are Synthroid and Levothroid. Manufacturers of unapproved oral levothyroxine sodium drug products without an NDA pending with the FDA must cease distribution by August 14, 2001.
August 2001 Update
Graves' disease is the most common cause of hyperthyroidism, an overactivity of the thyroid gland that results in too much thyroid hormone circulating through the body. The high thyroid level raises the body's metabolism, causing frequent bowel movements, increased heart rate, irritability, and anxiety, as well as an increased appetite partnered with weight loss. In addition, about one in five people with Graves' disease has bulging eyes. The condition is most common in young to middle-aged women.
Doctors usually treat Graves' disease with antithyroid medicines, radioactive iodine treatment, or surgery. The goal of treatment is to induce long-term remission, that is, to permanently reduce the amount of hormone the thyroid gland produces. Most often, patients find antithyroid medicines effective while they are on them, but hyperthyroidism often returns once the drugs are stopped. Radioactive iodine and surgery, on the other hand, destroy or remove so much of the thyroid gland that it no longer produces enough thyroid hormone. As a result, patients need to take thyroid pills for the rest of their lives. Until now, it has been difficult for physicians to predict which treatment will be more effective for which patients.
A new study, published in the March 2000 The Journal of Clinical Endocrinology & Metabolism, shows that patients under 40 and men do not respond as well to antithyroid medicines, and that men are less likely to be successfully treated with only one dose of radioiodine therapy. The researchers followed 423 patients for six months after they completed therapy. Of the patients, 314 received antithyroid medicines (usually an 18-month course of carbimazole) and 109 received radioiodine therapy.
Of the patients taking antithyroid medicines, only 37% remained in remission six months after treatment. Of those, men were significantly less likely than women (20% vs. 40%) to remain in remission, and patients younger than 40 were significantly less likely than patients over 40 (33% vs. 48%) to stay in remission. Men were also significantly less likely than women (47% vs. 74%) to enter remission after one dose of radioiodine therapy.
In response to these findings, the researchers proposed that men and patients younger than 40 receive early treatment with radioiodine therapy or surgery, since antithyroid medicines are unlikely to lead to remission. In addition, they suggest further research to investigate whether higher initial doses of radioiodine may be appropriate for male patients.
To learn more about Graves' disease, see page 844 of the Family Health Guide.
Researchers have long noted that low thyroid function (hypothyroidism) during pregnancy is associated with neuropsychological development problems in babies. A recent study published in the New England Journal of Medicine has shown that, in fact, hypothyroidism in pregnant women can negatively affect their children's performance on neuropsychological tests. And in fact, this effect may be noted even when a woman's thyroid function is only slightly below normal and without symptoms.
This research suggests that it may be worthwhile to test thyroid function in all pregnant women. Treating a woman for this condition will not only benefit her baby, but may also help women with unrecognized hypothyroidism who have no symptoms yet. 64% of the women in this study who had undiagnosed low thyroid function during pregnancy were shown to have developed confirmed hypothyroidism at follow-up 11 years later. While testing all pregnant women for low thyroid function is not yet standard practice, this research suggests that it may be in the future. If you are pregnant and have concerns about this information, talk with your doctor.
If you are a woman and you know you have low thyroid function and are of childbearing age, be sure to work closely with your doctor to keep your condition under control. If you do become pregnant, this becomes even more important. For more information on low thyroid function, see page 848 in the Family Health Guide.
A recent study has revealed that calcium carbonate may reduce the body's ability to absorb the thyroid medication levothyroxine. The people who are probably most affected by this discovery are postmenopausal women, since they often end up taking both levothyroxine and calcium carbonate. However, anyone taking levothyroxine and calcium carbonate concurrently can experience the same effect.
Patients participating in the study ranged in age from 27 to 78 years old and were almost evenly divided between men and women. They all had hypothyroidism (low thyroid function) and were taking levothyroxine. During the study, they were asked to take 1,200 mg of calcium carbonate daily over a three-month period. The majority of patients had significantly lower levels of thyroxine by the end of this period. They were then asked to discontinue taking the calcium carbonate, and their thyroxine levels were measured again after two months. At the end of the two-month period, their thyroxine levels were found to have returned to normal range.
In light of the fact that patients participating in the study were instructed to take the calcium carbonate daily with the levothyroxine on an empty stomach, researchers believe that the acidity level in the stomach may be a factor in how much levothyroxine is absorbed by the body. Researchers have suggested that one way to curb calcium carbonate's effect on levothyroxine is to take the calcium carbonate after a meal in order to optimize the bodys absorption of levothyroxine. They add that if while taking calcium carbonate and levothyroxine concurrently, a patient's thyrotropin level rises, it would be advisable to separate the times at which he or she takes calcium carbonate and levothyroxine on a given day. In some cases, physicians might want to increase the dosage of levothyroxine, to compensate for the effects of calcium carbonate.
October 2000 Update