by Mary J. Shomon

The story broke on May 3, 2001, here at my About Thyroid site, when I published the story Synthroid Has a Long History of Problems, Says FDA, in Denial Letter." I had obtained the letter from an inside source a copy of the April 26, 2001 letter in which the FDA had officially denied Synthroid's request to bypass new drug application and be declared "generally recognized as safe and effective."

The letter outlined various concerns of Synthroid's stability, potency and reliability for years. (Read the letter now -- note: the letter is in PDF format.)

Then, the Stop Patient Abuse Now Coalition and Gray Panthers joined forces to help "shift the balance of power from drug industry executives and their friends in Congress to the consumers who need relief," by calling for campaigns against several drugs, including Synthroid. The strategy is intended to raise the financial stakes for drug manufacturers that engage in anti-competitive or anti-consumer behavior in order to avoid competition. Read more about it now.

On May 25, 2001, Levoxyl became the second levothyroxine drug to receive FDA approval. Thyroid patients now had two FDA-approved levothyroxine products to choose from. With an average levothyroxine approval taking nine to ten months, and Synthroid still not having filed their new drug application, the key question for patients was what would happen in August when Synthroid still had not received approval, but the FDA deadline arrived.

On June 1, 2001, the Wall Street Journal published an article on the front page of the Marketplace section, titled "FDA Could Make Abbott Pull Synthroid, Popular Thyroid Drug, From the Market." (Note: The full text of this article was republished by MSNBC at their site, at http://www.msnbc.com/news/581223.asp).

In that article, reporter Chris Adams wrote: "a spokeswoman for the FDA said the regulatory notices the agency has published on Synthroid and its competitors 'don't include a provision' related to simply submitting an application by Aug. 14.

The agency has not decided what it would do if the Aug. 14 deadline came and went before the drug received approval. But it would not rule out asking for the drug's removal and noted that there are two other approved drugs in Synthroid's class that could fill any void left by Synthroid." I was also interviewed for background on that article, and was quoted several times.

The Wall Street Journal coverage opened up a firestorm of coverage and controversy. I was interviewed as a patient advocate by CBS radio news network, the ABC radio news network, WebMD, CBS radio in New York and ABC television on Friday.

In the meantime, on Friday, June 1, Abbott, manufacturer of Synthroid, issued its own press release, titled Abbott Response to News Reports on Synthroid. In their release, they directly contradict the FDA's denial letter, claiming that "the safety and efficacy of Synthroid has been extensively studied and validated."

In the April 26, 2001 letter, however, the FDA has said "The history of potency failures...indicates that Synthroid has not been reliably potent and stable."

The FDA also wrote to Synthroid's manufacturers, "Although you claim that Synthroid has been carefully manufactured, the violations of current good manufacturing practices discussed above indicate that Knoll has not always manufactured Synthroid in accordance with current standards for pharmaceutical manufacturing."

Interestingly, Abbott also includes the following quote: "Synthroid is a tried and trusted product with decades of use and physicians and patients should continue to have confidence in Synthroid," said Leonard Wartofsky, M.D., chairman, Department of Medicine, Washington Hospital Center, Washington, D.C. "It would be dangerous for patients if Synthroid were removed from the market."

Readers should be advised that Leonard Wartofsky, MD, is also an official representative of Synthroid and affiliated with the manufacturer. He was in fact in attendance at meetings with the FDA regarding Synthroid, and FDA records list him as a representative of Knoll/Synthroid. (See FDA's Synthroid Meeting Minutes in PDF format).

On Friday June 1, 2001, the endocrinology community issued a press release, weighing in on the issue. Synthroid Should Remain on the Market, Says the American Association of Clinical Endocrinologists (AACE). In this release, AACE, objected to the idea of Food and Drug Administration (FDA) withdrawing Synthroid from the market, stating "AACE is greatly concerned that the precipitous removal of the drug would create a massive and expensive burden for both patients and physicians alike.

Synthroid patients would have to visit physicians for an alternative medication. This would also require a significant change in pharmacy orders. Moreover, patients will be confused and unnecessarily alarmed over the safety of the drug. Dr. Cobin noted that clinical endocrinologists have not encountered unusual problems in prescribing Synthroid and, in fact, count on its reliability." (Dr. Cobin is Rhoda H. Cobin, MD, FACE, AACE's President.)

Later in the release, Dr. Cobin says: ``This is not about favoring one product over another, but what is best for our patients and the least costly and burdensome for our health care system." Interestingly, readers should be advised that Synthroid is prominently listed on the Sponsors Page of the American Association of Clinical Endocrinologists.

Also on June 1, 2001, the Gray Panthers issued another release, Gray Panthers Challenge Abbott Labs and American Thyroid Association To Answer FDA Concerns Regarding Safety and Effectiveness of Synthroid.

Here, their release reports on a letter sent to Abbott asking the company to respond to FDA concerns regarding the safety and effectiveness of Synthroid, concluding: "Unless we receive satisfactory answers to the questions posed in this letter, we believe your product should be removed from the market."

Gray Panthers Executive Director Tim Fuller said in the release "The FDA clearly stated that a New Drug Application for Synthroid must be approved by August, not just submitted. We should not allow Abbott to ignore the law for its own convenience while patient safety is at risk, especially since safe, effective, and approved alternatives are available."

Associated Press issued its own story late in the afternoon on Friday, June 1, 2001, Popular Thyroid Drug Faces Deadline. This story basically recapped the ongoing controversy.

Over the weekend, the coverage continued. Both the Boston Globe and Philadelphia Inquirer featured recap coverage:

• Thyroid drug's safety queried: FDA warns of dosage problems (Boston Globe, 6/2/2001)

Meanwhile, the debate continued on Monday, June 4, with another press release. American Thyroid Association, The Endocrine Society, and ThyCa Call for Continued Availability of Thyroid Hormone Products. In this release, The American Thyroid Association, The Endocrine Society, and ThyCa: Thyroid Cancer Survivors' Association urged the FDA to maintain the uninterrupted availability of Synthroid.

Says the release: "The American Thyroid Association, The Endocrine Society, and ThyCa recognize that the reason that Synthroid and some other thyroxine preparations have not yet received FDA approval is logistical, not medical."

Interestingly, this statement again ignores the FDA's stated concerns in their letter, in which the FDA wrote to Synthroid: : "...patients using Synthroid have experienced significant, unintended variations in their doses of levothyroxine sodium...these variations are not conducive to proper control of hypothyroidism."

Variations in dosages are of concern to all thyroid patients, but are particularly a concern for thyroid cancer survivors, who rely on stable doses to suppress thyroid function, a key means of preventing thyroid cancer recurrence.

It also should be noted that all three organizations are recipients of funding and support from Synthroid/Knoll.

The American Thyroid Association prominently lists Synthroid on its Sponsors Page. According to a phone call on Monday, 6/4/01 with Nancy Chill, Director of Development and Client Services for the Endocrine Society, the Endocrine Society is a recipient of corporate support from Synthroid. And the Thyroid Cancer Survivors' Association has received funding and support from Synthroid, including a booth presence at its annual conference for thyroid cancer survivors.

Given that the thyroid professional and patient organizations all seem to be coming from a position where their credibility is influenced by pharmaceutical funding, what can patients believe?

And ultimately, how can patients answer the most important question: What does this mean for them?

The answer to that question is not entirely certain.

We do know that there are two FDA-approved levothyroxine products already on the market -- Unithroid and Levoxyl -- that will not be going away anytime soon, and have been demonstrated to be consistent and reliable, according to FDA standards.
We also do know that it's not likely that Synthroid can file for new drug application and receive approval in time for the August, 2001 deadline, given that the application process usually takes nine to ten months from receipt by the FDA.

So, does that mean Synthroid will be pulled off the market?

With an estimated six to eight million patients in the U.S. taking the product, and hordes of corporate lobbyists working every angle on their behalf, it's not likely.

Synthroid may receive some sort of extension from the FDA that will allow the product to continue to be sold after the deadline.

We also know that ultimately, even if the product was taken off the market for a period of time, Synthroid is likely to end up receiving FDA approval within the next year.

What Should Patients Do?

If you are a new thyroid patient who is being prescribed levothyroxine for the first time, you may wish to ask your doctor to prescribe one of the approved levothyroxine products -- Unithroid or Levoxyl -- rather than Synthroid, which has an uncertain future at present. According to research at Drugstore.com, Levoxyl is currently the less expensive product.

If you are a thyroid patient on Synthroid who is experiencing symptoms, having fluctuations in your TSH levels from test to test, or you're simply just not feeling well, you may also wish to explore with your doctor the possibility of switching to one of the approved levothyroxine products -- Unithroid or Levoxyl -- to see if the consistency and stability of dosage helps alleviate symptoms and stabilize your condition.

If you are a thyroid patient who is taking Synthroid and you are stabilized and not experiencing fluctuations or symptoms, then you should talk with your physician about any concerns you may have, stay up on the latest developments concerning Synthroid's approval and availability, and consider developing a contingency plan with your physician in the event that Synthroid is pulled off the market in August should it not meet the FDA drug application deadline.

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