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Thyroid Drug's Safety Queried; FDA Warns Of Dosage Problems

June 6, 2001

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 Smoter in an interview.

Although the FDA has the authority to pull the drug from the market,

that action appears unlikely.

FDA spokeswoman 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. 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.

Copyright 2001 The Boston Globe. All rights reserved.

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