||The Third Most Prescribed Drug In The US Lacks Necessary Approval To Remain On Market
Popular Drug Must Comply With FDA Or Be Pulled From Market On August, 2001
Hypothyroidism, a disease in which the thyroid gland does not produce
sufficient thyroxine, affects up to 24% of the older population,(1) most of
them women. Symptoms range from cold intolerance and weight gain to
cardiovascular disease and dementia. It is estimated that 8 million people are
being treated with levothyroxine sodium, familiar to most people as the drug
Synthroid® (levothyroxine sodium tablets, USP).(2) Synthroid, the #3
prescribed brand in America, with an estimated 85% share of the market, does
not have the approved New Drug Application (NDA) it needs to remain on the
market.(3) Another brand of Synthroid, Unithroid (levothyroxine sodium tablets, USP)
received its NDA in August of 2000. To date, Unithroid is the first and only
oral levothyroxine sodium product approved as safe and effective by the FDA.
Levothyroxine sodium, a narrow therapeutic index (NTI) drug, is titrated
in very small increments until the patient is optimized. From then on, the
patient is on the drug for life and the dosage is retitrated from time to
time. Bioequivalence between levothyroxine sodium brands has never been
established, so it is recommended that patients stay on the same brand
throughout their course of therapy.
Many patients and professionals are unaware that levothyroxine sodium has a long history of
stability, potency, and consistency issues leading to recalls by the FDA. It
is a notoriously unstable compound and difficult to produce. Since 1991, there
have been at least 10 recalls of levothyroxine, involving 150 lots and 100
million tablets.(4) Issues ranged from the tablets having less active
ingredient than indicated, to the failure of medication to maintain its
potency through the expiration date. In addition, because levothyroxine sodium
was available prior to the NDA approval process, it was not subject to the
same strict regulations as FDA-approved drugs with New Drug Applications
(NDAs). Therefore, manufacturers were able to reformulate the product,
resulting in potency fluctuations of up to 30%.(4) The potential for these
issues to negatively impact patients is vast. In addition, in a recent large-
scale study, it was shown that approximately 40% of the participants who were
on thyroid hormone had abnormal thyroid test results.(5)
As a result of the problems stemming from levothyroxine sodium's inherent
instability, the FDA issued a mandate in August 1997 requiring that all
manufacturers of levothyroxine sodium have a complete and approved NDA filed
by August 2000 to continue marketing.(4) At the request of Knoll
Pharmaceutical Company, maker of Synthroid, the deadline was extended 1 year.
Currently, the deadline is set at August 2001. After that, any levothyroxine
sodium product without an NDA may be pulled from the market by the FDA.
To date, only the manufacturer of Unithroid has complied with the FDA
mandate and received NDA approval. This means that there is only 1
levothyroxine sodium currently available that the FDA has approved as safe and
effective, having satisfactorily addressed all issues regarding stability,
potency, dissolution, and bioavailability. Unithroid was previously produced under the names levothyroxine sodium and Thyrox for more than 10 years, with 1
billion tablets manufactured without a recall. Unithroid is now available by
prescription only, and can be found at your local pharmacy. Patients with
hypothyroidism should ask their physicians about their treatment options.
- References: 1. Sawin CT. Subclinical hypothyroidism in older persons. Clin
Geriatr Med. 1995;11:231-238.
- 2. Dong BJ, Hauck WW, Gambertoglio JG.
Bioequivalence of generic and brand-name levothyroxine products in the
treatment of hypothyroidism. JAMA. 1997;277:1205-1213.
- 3. Scott Levin.
Prescription Source Audit, 2000.
- 4. Department of Health and Human Services,
Food and Drug Administration. Prescription drug products; levothyroxine
sodium. Federal Register. 1997;62. Available at http://wais.access.gpo.gov.
- 5. Canaris GH, Manowitz NR, Mayor G, Ridgway, CE. The
Colorado disease prevalence study. Arch Int Med. Available at:
http://archinte.ama-assn.org. Accessed July 13, 2000.
WARNING: Thyroid hormones, including UNITHROID, either alone or with other
therapeutic agents, should not be used for the treatment of obesity. In
euthyroid patients, doses within the range of daily hormonal requirements are
ineffective for weight reduction. Larger doses may produce serious or even
life threatening manifestations of toxicity, particularly when given in
association with sympathomimetic amines such as those used for their anorectic
- Levothyroxine sodium is contraindicated in patients with untreated thyrotoxicosis,
acute myocardial infarction, uncorrected adrenal insufficiency, or
hypersensitivity to any of its inactive ingredients
- Should not be used to treat infertility unless condition is associated
- Use with caution in patients with cardiovascular disease
- Adverse reactions are primarily those of hyperthyroidism due to
overdose, such as palpitations, arrhythmias, heat intolerance, weight
loss, tremors, nervousness, diarrhea, abdominal cramps, fatigue,
headache, and menstrual irregularities
- Reactions to product excipients, such as rash or urticaria, may occur
- Partial hair loss that may occur during initial months of therapy is
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