Executive Summary

SMITHKLINE BEECHAM'S TAGAMET I.V. UPPER GI BLEEDING INDICATION approved by FDA, the company announced Dec. 9. FDA cleared the supplemental NDA on Nov. 13, but SmithKline Beecham waited to make the announcement until the American Society of Hospital Pharmacists meeting in New Orleans. The approved label now indicates Tagamet (cimetidine) continuous infusion for "prevention of upper gastrointestinal bleeding in critically ill patients." Tagamet is the first H[2] antagonist to carry the indication. "For reasons that are not completely clear, critically ill hospitalized patients are at high risk of developing upper gastrointestinal tract damage as a complication of severe illness or traumatic injury," SmithKline Beecham said. "Studies have shown that nearly 90% of cardiac surgery patients and up to 100% of severe injury patients may suffer some damage to the lining of the upper GI tract. In up to 30% of patients, this damage causes clinically significant bleeding that may be fatal," the company stated. The condition is also found in "critically ill patients suffering from shock, infection, burns, and central nervous system injury." The new indication is the second for Tagamet this year. The oral dosage form of the drug was approved March 7 for gastroesophageal reflux disease (GERD)("The Pink Sheet" May 6, In Brief). Tagamet's U.S. patent expires in May 1994. SmithKline Beecham filed for the new indication on April 10, 1990. FDA's Gastrointestinal Drugs Advisory Committee recommended approval of the new indication on July 25 ("The Pink Sheet" July 29, p. 4). The new Tagamet label includes data from the company's TA-SO2 study, which the advisory committee found convincing. That 131- patient trial showed a 14% incidence of bleeding in Tagamet patients versus 33% in placebo patients. The approved dose for the new indication is 50 mg/hr continuous infusion. Patients with low creatinine levels should use half the recommended dose, the label says. "Treatment beyond seven days has not been studied." One issue of concern for the advisory committee was a possible increase in mortality for patients in the study on Tagamet. The committee voted that there was an increased risk with cimetidine, but agreed that the risk did not preclude approval of the drug. SmithKline Beecham's press release announcing the approval notes that "bleeding associated with mortality was observed in one of the nine patients receiving Tagamet, compared to four of 22 placebo-treated patients."