BOSTON (Boston Globe) - The leading prescription medicine for hypothyroidism, taken by millions of Americans, has been plagued by problems that could harm the health of those who take it, according to the Food and Drug Administration.

The composition of the drug, Synthroid, has been changed repeatedly and the potency of the drug varies so much that, in the past, patients have gotten too little of the active ingredient, the agency said in a letter to the manufacturer that was made public this week and first reported in the Wall Street Journal.

The drug has been on the market for 42 years, predating approval requirements of the FDA. In 1997, the agency notified the makers of Synthroid and two other thyroid drugs that they would have to secure the agency's formal approval or stop selling the drug by this August.

In its April 26 letter to Abbott Laboratories, the FDA said it would not waive that requirement because of a "long history of manufacturing problems" and "potency and stability problems that impair the safety and effectiveness of Synthroid." Abbott officials defended the drug and said the company would submit a formal application for FDA approval shortly to ensure that the drug stays on the market. The approval process usually takes about 10 months.

"The safety and efficacy of Synthroid has been extensively studied and validated," the company said in a statement. It noted that than more than 8 million patients use the drug daily.

"All of the things cited in the FDA's letter have been resolved," added Abbott spokeswoman Jennifer Smoter in an interview.

Although the FDA has the authority to pull the drug from the market, that action appears unlikely.

FDA spokeswoman Susan Cruzan said, "We are looking at all of our options and haven't made a final decision on what should happen if the drug doesn't have a final approval" by Aug. 14. "We have to take into consideration the patients' needs." Patients take the drug to supplement or replace hormones that regulate many bodily functions but which are not sufficiently produced by a deficient thyroid gland. The disorder is characterized by a retarded rate of metabolism in sufferers. The FDA's concerns stem largely from manufacturing problems that have periodically led to pills containing less of the drug than advertised.

Patients who get too little of Synthroid may experience symptoms ranging from lethargy to depression.

The problems that the FDA noted in its letter occurred while the drug was manufactured by Knoll Pharmaceutical Co. Abbott acquired the drug in March when it bought Knoll.

Knoll had sought to avoid the formal approval process by submitting information that the drug is "generally recognized as safe and effective." The FDA rejected that petition.

The two other manufacturers of thyroid drugs with the same generic ingredient, levothyroxine sodium, provided the FDA with the detailed safety and effectiveness studies needed for formal approval and have received it.

The makers of those drugs, Levoxyl and Unithroid, also had had problems with variations in potency.

Dr. Kenneth Blanchard, an endocrinologist in private practice in Newton, said he had not seen problems with the drug's potency in his patients who use Synthroid, but that he regularly used Levoxyl and Unithroid instead because they are less expensive and contain fewer allergens among their inactive ingredients.

He said he switched a patient off Synthroid after she called with concerns following news reports about the FDA's action.

"I expect I'll see more of those requests next week," he said Saturday.

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