STREPTOKINASE I.V. APPROVED FDA LABELING NOTES 47% MORTALITY REDUCTION

STREPTOKINASE I.V. APPROVED FDA LABELING NOTES 47% MORTALITY REDUCTION among acute myocardial infarction patients treated within one hour of the onset of chest pain. The mortality experience data is derived from the large Italian trial (the GISSI study). FDA approved streptokinase I.V. on Nov. 5 for treatment of heart attack. The product has been approved since 1982 for that indication, but only via catheter administration, and previous labeling warned in bold type that reduced mortality had not been shown. "Streptokinase is indicated for use in management of acute myocardial infarction in adults for the lysis of intracoronary thrombi, improvement of ventricular function and reduction of mortality when administered by either the intravenous or intracoronary route," the revised labeling states. "Earlier administration of streptokinase is correlated with greater clinical benefit." The product's therapeutic benefit appears to revolve around the "earlier administration" aspect of the new indication. A same-day press release by Hoechst-Roussel, one of two companies to receive approval, notes that I.V. streptokinase "will enable treatment of heart attack victims to begin at least an hour sooner, resulting in a critical time savings in the clot-dissolving, and life-saving process." The nearly 12,000-patient GISSI study established mortality reduction with streptokinase as time-dependent -- a 23% decrease occurred in patients treated within three hours after the onset of chest pains and 17% among those treated between three and six hours. An overall 23% decrease in mortality resulted when the results of all studies were pooled. In addition, studies measuring left ventricular function showed an ejection fraction in the streptokinase group three to six percentage points higher than in the control group. The recommended dosing is 1.5 mil. IU administered within 60 minutes of, or as soon as possible after the onset of symptoms. "The rate of reocclusion of the infarct-related vessel has been reported to be approximately 20%," the labeling continues. "When the reinfarctions were evaluated in studies involving 8,800 streptokinase-treated patients, the overall rate was 3.8% (range 2-15%). In over 8,500 control patients, the rate of reinfarction was 2.4%." Adverse reactions observed in conjunction with the use of I.V. streptokinase include bleeding, allergic reactions and fever. The overall incidence of major bleeding using high-dose infusion is 1.2%, according to the approved labeling. "In three studies in which anticoagulation was optional following intravenous administration of streptokinase for acute myocardial infarction, the incidence of major bleeding ranged from 0.3-6.2%," labeling states. "In 21 studies in which anticoagulation was compulsory, the incidence of major bleeding ranged from 0-16%." Intracranial bleeding incidents associated with high doses of Genentech's TPA product Activase were discussed by FDA's Cardio-Renal Drugs Advisory Committee at its May 29 meeting. At that meeting, the committee recommended I.V. streptokinase for approval and asked for more information on Activase. Hoechst-Roussel and KabiVitrum received approval to market I.V. streptokinase in the U.S. under the brand names Streptase and KabiKinase, respectively. SmithKline is the exclusive distributor for the KabiVitrum product under an agreement announced Oct. 29. FDA's Nov. 5 approval letter to KabiVitrum advised the company that future advertising and promotional labeling should be submitted to the agency for review prior to its dissemination. "All promotional claims must be consistent with and not contrary to approved labeling," Office of Biologics Research & Review Director Elaine Esber, MD, wrote. "No comparative promotional claims of superiority over other similar product should be made unles data to support such claims are submitted to and approved."