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Back To Vidyya 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 effects.

  • 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 with hypothyroidism
  • 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 generally transient

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Editor: Susan K. Boyer, RN
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