Aug 11 2004
Two organizations representing more than 5,400 clinical endocrinologists today warned patients taking thyroid medication, prescribing physicians, and pharmacists dispensing these drugs that clinically important differences do, in fact, exist between one recently approved generic levothyroxine preparation and the most widely prescribed brand of levothyroxine.
The members of these organizations, the American Thyroid Association and the American Association of Clinical Endocrinologists, specialize in treatment of hormonal disorders.
Levothyroxine is taken by more than 13 million Americans to treat an underactive thyroid, thyroid gland enlargement, nodules, or cancer. In June, the Food and Drug Administration (FDA) ruled that several generic levothyroxine preparations had the same clinical effect and safety profile as certain branded products. As a result, pharmacists may substitute a patient's current levothyroxine preparation for another, sometimes without their physician's approval.
According to bioequivalence data used to acquire FDA approval, one recently approved generic levothyroxine preparation (Sandoz Levothyroxine Sodium) is significantly more potent than the most widely used brand of levothyroxine (Synthroid(R)). Information from bioequivalence studies submitted to the FDA show that the new generic may be as much as one-eighth more potent (+12.5%) than the widely prescribed branded product.
Furthermore, levothyroxine is a drug known to have a narrow toxic-to- therapeutic ratio with significant clinical consequences of even minor excessive or inadequate dosing. Potential adverse events include symptoms, osteoporosis, atrial fibrillation, worsening of heart disease, preterm delivery in pregnancy, impaired fetal brain development, and high cholesterol.
"Unfortunately, this information confirms our concern that current FDA standards defining the equivalence of levothyroxine products is too lax," said Carlos Hamilton, MD, AACE President. "Switching between two products could compromise the effectiveness of treatment and even result in serious side effects."
The ATA and AACE have repeatedly expressed their concerns about the FDA's recent decision to approve generic substitutes for levothyroxine products and its implications for the millions of Americans who depend on this drug. The societies have also made public their disappointment that the FDA made their decision before considering the input offered by clinical endocrinologists, the recognized experts who care for thyroid patients.
Both the FDA and the societies recommend that patients switching between levothyroxine products have repeat thyroid blood testing to be certain that the treatment dose remains effective and safe. "Under a policy of allowing generic levothyroxine substitution," said Gregory Brent, MD, ATA Secretary, "more frequent thyroid function testing will be necessary. Regrettably, some patients and doctors will not even be aware of a change in preparation before adverse events occur."