Thyroid Experts Warn of Clinically
Important Differences in Potency
of FDA-Approved Levothyroxine Products
Generic bioequivalence data confirms medical
societies’ concern about recently approved generic levothyroxine
preparations
(FALLS CHURCH, VA)—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 (ATA) and the American
Association of Clinical Endocrinologists (AACE), 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®). 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 are 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.”
The ATA and AACE advise physicians caring for patients on levothyroxine
therapy to —
- Alert patients that their levothyroxine preparation may be
switched at the pharmacy,
- Encourage patients to remain on their current levothyroxine
preparation when possible,
- Ensure that patients understand if they receive a new levothyroxine
preparation that they will need to repeat a thyroid-stimulating
hormone (TSH) blood test four to six weeks later to determine
if they need further dose adjustment.
The societies also strongly urge pharmacists, pharmacies, and health
plans to respect the wishes of patients and physicians who choose
to continue the same levothyroxine preparation. They caution those
who dispense and pay for levothyroxine products that there can be
serious health consequences if patients and their doctors are not
fully informed about the potential risks of substitution and the
requirement for retesting if they choose to switch to another levothyroxine
preparation.
The ATA’s previous statements related to this matter can
be found on the ATA’s web site at: http://www.thyroid.org/professionals/advocacy/04_06_24_fda.html.
Founded in 1923, the ATA is a professional society of 900 U.S.
and international physicians and scientists who specialize in the
research and treatment of thyroid diseases. The Association is dedicated
to promoting scientific and public understanding of the biology
of the thyroid gland and its disorders, so as to improve methods
for their prevention, diagnosis, and management. The ATA fosters
excellence in research, patient care, and education of patients,
the public, and the medical and scientific communities while guiding
public policy about the prevention and management of thyroid diseases.
AACE is a professional medical organization with over 4,900 members
in the United States and 70 other countries. Founded in 1991, AACE
is dedicated to the optimal care of patients with endocrine problems.
AACE initiatives inform the public about endocrine disorders. AACE
also conducts continuing education programs for clinical endocrinologists,
physicians whose advanced, specialized training enables them to
be experts in the care of endocrine disease, such as diabetes, thyroid
disorders, growth hormone deficiency, osteoporosis, cholesterol
disorders, hypertension and obesity.
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