http://www2.massgeneral.org/pharmacy/Newsletters/2001/October_2001/Why_do_we_continue_to_write_for_Synthroid.htm
Why do we continue to write for Synthroid?
Volume XI, Issue 8
Harold J. DeMonaco, M.S., Director of Drug Therapy Management
Levothyroxine products have been touted as having a low therapeutic index and as such many clinicians have prescribed what they believe to be the most consistent product available, Synthroid. We have recently examined the prescribing practices of PCHI physicians participating in contract with local insurers and confirmed that Synthroid is the most prescribed "branded generic" product in the network. But Synthroid is a brand of levothyroxine that is not recognized as safe and effective by the FDA. This is puzzling since there are two FDA-approved products (Unithroid and Levoxyl) available. Why would physicians fail to use FDA-approved products and continue to use a product which the FDA categorized as failing batch-to-batch reliability and adequate stability testing?
The history of Synthroid reads like a "made-for-TV" movie. Thyroid replacement drugs have been available since the late 1930's but without much in the way of Food and Drug Administration oversight. Drugs that were commercially available prior to the 1938 establishment of the modern FDA were grandfathered and allowed to continue to be sold commercially even though they have not met regulatory standards. Synthroid became the largest selling brand name levothyroxine in the United States, capturing over 85% of total sales of over $600 Million annually during the early 1990's.
In 1986, Flint Laboratories, the then-manufacturer of Synthroid, contracted with a researcher at the University of California to conduct a study that they hoped would demonstrate that Synthroid was a better product than the major competitors' products. Unfortunately, when the study was completed in 1990, it clearly showed that all available brands of levothyroxine were, in fact, equal. In the intervening years, Flint Laboratories was sold to Boots Pharmaceuticals. When the researchers attempted to publish their results, Boots Pharmaceuticals exercised a clause in the contract that required their approval of the publication. The publication of the results of the study would have theoretically resulted in a switch to less expensive competitor products and a potential loss of the near monopoly Boots had on the thyroid replacement market. Boots Pharmaceuticals was sold to Knoll. Knoll persisted in their opposition to the publication of the study. Intervention on the part of the FDA finally broke the impasse. The manuscript was eventually published in 1997 in the Journal of the American Medical Association. With the publication came more than 60 class action suits alleging consumers had paid 2-3 times what they should have paid for levothyroxine as a result of the suppression of the University of California study from 1990 to 1997. Knoll eventually settled the case for $135 million.
In the meantime, the FDA began to take issue with many of the claims being made by the manufacturers of Synthroid of the superiority of their product over the competitors less expensive brand. Armed with the results of the University of California study and others, the FDA concluded that not only were the available brands of levothyroxine all equivalent, they were all substandard, including Synthroid. In 1997, the FDA issued a revocation of the approval status for all brands of levothyroxine, giving manufacturers until August 2001 to file a so-called New Drug Application or NDA. The NDA process requires manufacturers to demonstrate the safety and effectiveness of their product. Knoll continued to insist that their product was safe and effective and steadfastly refused to file for an NDA. In April 2001, Abbott Laboratories, having just purchased Knoll Pharmaceuticals, indicated they would file for an NDA for Synthroid and did so. The FDA has yet to opine.
But the competition was not sitting idly by. In August 2000, the FDA issued its first NDA for a levothyroxine product from Jerome Stevens Pharmaceuticals under the brand name Unithroid. Jones Pharma obtained FDA approval to market their version of levothyroxine, Levoxyl, on May 25, 2001.
Despite the availability of two FDA-approved levothyroxine products, physicians continue to prescribe Synthroid, a non-FDA-approved product. It is also twice as expensive as the FDA-approved products. We can only assume that effective marketing on the part of the manufacturers is the cause of this prescribing pattern nationwide. It will be interesting to track prescribing trends once the FDA renders a decision on Synthroid.
References:
1. Dong BJ. Hauck WW. Gambertoglio JG. Gee L. White JR. Bubp JL. Greenspan FS. Bioequivalence of generic and brand-name levothyroxine products in the treatment of hypothyroidism. [see comments]. JAMA. 1997; 277: 1205-1213.
2. Rennie D. Thyroid storm. JAMA. 1997; 277: 1238-43.
3. http://www.fda.gov/cder/guidance/4647fnl.htm
Why do we continue to write for Synthroid?
Volume XI, Issue 8
Harold J. DeMonaco, M.S., Director of Drug Therapy Management
Levothyroxine products have been touted as having a low therapeutic index and as such many clinicians have prescribed what they believe to be the most consistent product available, Synthroid. We have recently examined the prescribing practices of PCHI physicians participating in contract with local insurers and confirmed that Synthroid is the most prescribed "branded generic" product in the network. But Synthroid is a brand of levothyroxine that is not recognized as safe and effective by the FDA. This is puzzling since there are two FDA-approved products (Unithroid and Levoxyl) available. Why would physicians fail to use FDA-approved products and continue to use a product which the FDA categorized as failing batch-to-batch reliability and adequate stability testing?
The history of Synthroid reads like a "made-for-TV" movie. Thyroid replacement drugs have been available since the late 1930's but without much in the way of Food and Drug Administration oversight. Drugs that were commercially available prior to the 1938 establishment of the modern FDA were grandfathered and allowed to continue to be sold commercially even though they have not met regulatory standards. Synthroid became the largest selling brand name levothyroxine in the United States, capturing over 85% of total sales of over $600 Million annually during the early 1990's.
In 1986, Flint Laboratories, the then-manufacturer of Synthroid, contracted with a researcher at the University of California to conduct a study that they hoped would demonstrate that Synthroid was a better product than the major competitors' products. Unfortunately, when the study was completed in 1990, it clearly showed that all available brands of levothyroxine were, in fact, equal. In the intervening years, Flint Laboratories was sold to Boots Pharmaceuticals. When the researchers attempted to publish their results, Boots Pharmaceuticals exercised a clause in the contract that required their approval of the publication. The publication of the results of the study would have theoretically resulted in a switch to less expensive competitor products and a potential loss of the near monopoly Boots had on the thyroid replacement market. Boots Pharmaceuticals was sold to Knoll. Knoll persisted in their opposition to the publication of the study. Intervention on the part of the FDA finally broke the impasse. The manuscript was eventually published in 1997 in the Journal of the American Medical Association. With the publication came more than 60 class action suits alleging consumers had paid 2-3 times what they should have paid for levothyroxine as a result of the suppression of the University of California study from 1990 to 1997. Knoll eventually settled the case for $135 million.
In the meantime, the FDA began to take issue with many of the claims being made by the manufacturers of Synthroid of the superiority of their product over the competitors less expensive brand. Armed with the results of the University of California study and others, the FDA concluded that not only were the available brands of levothyroxine all equivalent, they were all substandard, including Synthroid. In 1997, the FDA issued a revocation of the approval status for all brands of levothyroxine, giving manufacturers until August 2001 to file a so-called New Drug Application or NDA. The NDA process requires manufacturers to demonstrate the safety and effectiveness of their product. Knoll continued to insist that their product was safe and effective and steadfastly refused to file for an NDA. In April 2001, Abbott Laboratories, having just purchased Knoll Pharmaceuticals, indicated they would file for an NDA for Synthroid and did so. The FDA has yet to opine.
But the competition was not sitting idly by. In August 2000, the FDA issued its first NDA for a levothyroxine product from Jerome Stevens Pharmaceuticals under the brand name Unithroid. Jones Pharma obtained FDA approval to market their version of levothyroxine, Levoxyl, on May 25, 2001.
Despite the availability of two FDA-approved levothyroxine products, physicians continue to prescribe Synthroid, a non-FDA-approved product. It is also twice as expensive as the FDA-approved products. We can only assume that effective marketing on the part of the manufacturers is the cause of this prescribing pattern nationwide. It will be interesting to track prescribing trends once the FDA renders a decision on Synthroid.
References:
1. Dong BJ. Hauck WW. Gambertoglio JG. Gee L. White JR. Bubp JL. Greenspan FS. Bioequivalence of generic and brand-name levothyroxine products in the treatment of hypothyroidism. [see comments]. JAMA. 1997; 277: 1205-1213.
2. Rennie D. Thyroid storm. JAMA. 1997; 277: 1238-43.
3. http://www.fda.gov/cder/guidance/4647fnl.htm