A leading pharmaceutical manufacturer was asked by the Food and Drug Administration yesterday to agree to stop selling a widely prescribed antibiotic that, the FDA says, pointlessly causes reversible liver damage in thousands of users.
But Eli Lilly & Co. of Indianapolis immediately turned down the request. It said that neither scientific nor legal considerations warrant removal from the market of Ilosone, which is used to treat certain infectious diseases. The FDA said it intends to initiate legal action to halt sales.
Ilosone is a form of a popular and useful antibiotic called erythromycin and is sold at Dista Products Co., a Lilly division. The FDA request does not apply to rival versions, or salts, of erythromycin.
Last year alone, physicians wrote a reported 7.7 million new and refill prescriptions for Ilosone.The retail value was about $60 million.
Lilly introduced Ilosone in 1960. The National Institute of Health Clinical Center and New York Hospital of Cornell University discontinued its use in 1969. The Council of Drugs of the Maerican Medical Association said in 1971 that Ilosone was the only erythromycin associated with liver toxicity. Several Veterans Administration hospitals stopped stocking it.
In April 1973, the Health Research Group (HRG), which is financed by Ralph Nader's Public Citizen Inc., petitioned the FDA to stop sales of Ilosone on the ground that it was more toxic -- but no more effective than other erythromycins.
On the advice of a panel of outside experts, the FDA denied the petition on the ground that Ilosone appeared therapeutically superior to other erythromycins in a way that offset the risk of liver injuries, including hepatitis and jaundice. Also on the panel's advice, however, the FDA in 1974 ordered Lilly to warn in the labeling for physicians of a significantly higher risk of liver damage.
Last year, the FDA's Bureau of Drugs was told by two scientists, working under agency contracts, that the evidence of therapeutic superiority for Ilosone appeared to be invalid. In addition, the FDA evaluated adverse reactions associated with erythromycins and concluded that Ilosone was linked to 93 percent.
Last March, HRG director Sidney M. Wolfe told bureau director J. Richard Crout that the HRG was starting to prepare a second petition to halt Ilosone sales.
In the 6 1/2 years since the first petition, he estimated, "at least 100,000 people have needlessly suffered liver toxicity."
On Wednesday, the eve of the filing of the ptition, the FDA phoned Lilly to say that the agency was going to request voluntary withdrawal of Ilosone. FDA Associate Commissioner Wayne L. Pines said that agency officials had been gearing up for the action for weeks and hadn't known the HRG petition was about to be filed.
In a letter yesterday to Patricia Roberts Harris, secretary of health, education and welfare, Wolfe said the FDA's "educational moves" had done little to deter physicians from writing prescriptions for Ilosone, that 41 million prescriptions for it have been filled since his 1973 petition, and that the drug was causing 20 times as much liver damage as all other erythromycins.
He urged her to ban the drug in order to "put a stop to this outrageous . . . toll of thousands of avoidable drug injuries."
In Indianapolis, Lilly termed Ilosone "safe and effective." Millions have taken Ilosone "with no serious side effects," the firm said, adding that adverse reactions are "rare," have never been known to be fatal, and subside when medication is discontinued.