by Chris

Adams, staff reporter

WASHINGTON - The Food and Drug Administration has told the maker of Synthroid, one of the nation's most frequently prescribed drugs, that the medicine has a "history of problems" and cannot be recognized as "safe and effective."

The agency's statements raise the possibility that the 40-year-old drug, which has never been officially approved for use by the FDA, will be subject to regulatory action that could, in the extreme, include removal from the market - a process that could begin as early as August..

"Four years ago, the FDA said that makers of thyroid drugs like Synthroid, known generically as levothyroxine sodium, needed to get FDA approval for the drugs to continue marketing them. Abbott Laboratories, which acquired Synthroid's maker earlier this year, has said it will submit an application to the FDA detailing the drug's safety and efficacy and that it is confident the drug will be allowed to stay on the market...but it (the FDA) would not rule out asking for the drug's removal and noted there are two other approved drugs in Synthroid's class that could potentially fill any void left by Synthroid."

"The regulatory skirmishes between the FDA and Synthroid's maker date back a decade, when the drug was in different corporate hands. It is taken by patients who have hypothyroidism or other disorders of the thyroid, and such thyroid replacement therapy usually continue throughout the patient's lifetime."

"Synthroid went on the market more than four decades ago and never received formal approval from the FDA. Such approval was required, the FDA's spokeswoman said, but neither the agency nor the drug's current owner is certain why it was never received. In the mid-1990s, the FDA began compiling data on adverse events associated with the use of Synthroid as well as with the use of its competitors. In 1997, it noted that "almost every manufacturer" of such drugs had reported recalls because of potency problems."

"When such potency problems occur, the finely calibrated drug regimens that patients with thyroid problems need are likely to go astray, meaning their thyroids will function at less than the desired levels or go into overdrive - problems the FDA found in its review."

"Instead of submitting its own application, Synthroid's maker at the time - Knoll Pharmaceutical- submitted a 'citizen's petition' requesting that the FDA determine that Synthroid is 'generally recognized as safe and effective' and not subject to regulation as a new drug, FDA records show. In late April, however, the FDA replied to the petition, noting that the drug's composition has been changed repeatedly and that the drug 'has a long history of manufacturing problems,' including recalls and plant inspection violations from the early 1990s through 1998."

"The reply also said that a history of potency failures 'indicates that Synthroid has not been reliable potent and stable' and that the evidence 'suggests that Synthroid has stability, potency and consistency problems.' It concluded that when 'patients receive tablets that are filled with a product of unpredictable potency, therapy with levothyroxine sodium is neither safe nor effective..."

"This week, a consumer activist group called the Gray Panthers wrote Abbott asking why preparing an application for the FDA has taken four years..."

"An Abbott spokeswoman said that during the two most recent inspections of its Synthroid plant, the FDA found no violations in its manufacturing processes, and that the product has a four-decade track record with millions of patients using it. The company also said it will submit its application to the FDA 'shortly'."