FDA Calls for Cutting Dosage of AZT by 50%

Federal health officials recommended Tuesday that patients with AIDS or advanced AIDS-Related Complex take only half of the previously recommended dosage of the antiviral drug AZT, predicting that fewer patients would be forced to discontinue the drug because of its toxic side effects.

The Food and Drug Administration said that new labeling approved for the drug, also known as zidovudine, would state that it should be administered for long-term therapy at 600 milligrams a day, rather than the previously recommended 1,200 milligrams.

The FDA noted, however, that patients should receive the higher dose for at least one month before initiating the lower amount. It warned that the effectiveness of the lower dose on the neurological problems experienced by many AIDS patients still is unknown.

The recommendations resulted from a 2 1/2-year study that compared high and low doses of AZT among more than 500 patients. The study found that patients in the low-dose group tolerated the drug better than those in the high-dose group, without any loss of effectiveness.

“AZT remains the best available therapy for the disease,” said Dr. Michael Gottlieb, a Los Angeles physician whose practice is devoted almost exclusively to AIDS patients. “This new information on the lower dose should encourage patients with AIDS to choose it as the backbone of their medical regimen.”

The FDA action appears to resolve one of several roadblocks preventing doctors from administering the drug to certain patients. Some doctors have been concerned that insurers wouldn’t pay for the costly drug until the FDA broadened its labeling recommendations to include low-dosage recommendations.

Still unresolved, however, is whether physicians should administer AZT to two other groups--patients with early AIDS-Related Complex and those who have been infected with the human immunodeficiency virus and show some evidence of immune system damage but have not yet developed symptoms of the disease.

Preliminary results of two studies--announced with much fanfare by federal health officials last August--have shown the drug to be effective in arresting the progression of disease in patients with early symptoms and in delaying its onset in those without any symptoms.

But the results of the studies have not yet been published in a medical journal, and the Department of Health and Human Services has not issued new guidelines for physicians who treat these patients. The result, some doctors and patient advocacy groups have charged, is that thousands of patients around the country are being harmed because they are not receiving AZT while doctors wait for the studies to be published.

“It really isn’t fair to the practitioner--who is trying to give the best possible care to patients--to have no more information than what is in a press release,” said Jeff Levi, a spokesman for the New York-based Gay Men’s Health Crisis.

Brad Stone, an FDA spokesman, said that the agency only recently received data from the two AZT studies involving patients with early AIDS-Related Complex and those who are infected but asymptomatic and that it would not act until the material has been reviewed thoroughly. The FDA has scheduled an advisory committee meeting for Jan. 29 to discuss the application of AZT to those two groups.

AZT, the only antiviral drug approved to treat AIDS, has been in widespread use since late 1986 and was formally approved in March, 1987. It has been shown to prolong significantly the lives of patients with AIDS and AIDS-Related Complex and to reduce the frequency and severity of the infections that characterize the deadly disease.

But many patients taking the drug have experienced dangerous side effects, including a dramatic drop in the production of red blood cells--resulting in severe anemia--and a reduction in white blood cells to the extent that administration of the drug must be stopped.

“Today’s announcement means that fewer patients may have to discontinue AZT therapy because of serious side effects,” HHS Secretary Louis W. Sullivan said in a statement.

Further, the new recommendation is expected to reduce overall treatment costs, which run about $8,000 a year for patients taking the drug at higher doses, even after two separate 20% price cuts by the drug’s manufacturer, Burroughs Wellcome Co. of Research Triangle Park, N.C.

The dosage study, begun in December, 1986, and sponsored by the National Institute of Allergy and Infectious Diseases, compared two groups of 262 patients each. One group took 1,500 milligrams of AZT a day, which was the high dose used in early clinical trials of the drug, and the second group took 600 milligrams.

The FDA said that some physicians may already be prescribing the lower dosages because early findings from the study were publicly discussed last summer.