DUPONT's BREVIBLOC APPROVAL IS FOR SHORT TERM TREATMENT OF ATRIAL FIBRILLATION OR FLUTTER AND TACHYCARDIA; LAUNCH SET FOR FIRST QUARTER 1987

Dupont Critical Care's short acting beta blocker Brevibloc (esmolol) approval is for treatment of atrial fibrillation or flutter in surgical or other situations and for treatment of tachycardia, FDA-approved labeling states. The package insert says Brevibloc is "indicated for the rapid control of ventricular rate in patients with atrial fibrillation or atrial flutter in perioperative, postoperative, or other emergent circumstances where short term control of ventricular rate with a short-acting agent is desirable." The drug is also indicated "in compensatory sinus tachycardia where, in the physician's judgment the rapid heart rate requires specific intervention." Labeling specifies that Brevibloc "is not intended for use in chronic settings where transfer to another agent is anticipated." Dupont had sought approval for a prophylaxis indication. However, labeling does not include that claim. FDA's Cardio-Renal Drugs Advisory Committee recommended approval of the drug in September for prophylactic treatment in a group of high risk perioperative patients that was as yet undefined ("The Pink Sheet" Oct. 6, p. 5). The committee also advised that in order to support a general prophylactic claim for perioperative uses, additional data was needed to support the antieschemic effect of the drug in patients at lower risk. Regarding Brevibloc's use in supraventricular tachycardia, the committee said the claim should be limited to ventricular fibrillation and flutter. The short acting beta blocker was approved Dec. 31, exactly two years to the day after its December 1984 NDA submission. American Critical Care, acquired by Dupont in September, submitted the application. Dupont said Brevibloc will be launched to the trade during the first quarter of 1987. The prior to wholesalers is $18.50 per dose of 2.5 g (250 mg/mL) in 10 ml ampuls. The drug is supplied in boxes of one or ten. Labeling states that in two multicenter, randomized, double-blind, controlled studies comparing Brevibloc with placebo and propranolol, "maintenance doses of 50 to 300 mcg/kg/min of Brevibloc were found to be more effective than placebo and about as effective as propranolol, 3-6 mg given by bolus injections, in the treatment of supraventricular tachycardia, principally atrial fibrillation and atrial flutter." Labeling adds that "about 60-70% of the Brevibloc-treated patients had a desired therapeutic effect (either a 20% reduction in heart rate, a decrease in heart rate to less than 100 bpm, or, rarely, conversion to NSR)." The most important adverse effect with Brevibloc is hypotension. The labeling warns that "in clinical trials 20-50% of patients treated with Brevibloc have had hypotension" and "about 12% of the patients have been symptomatic (mainly diaphoresis or dizziness)." The reaction is dose-related "so that doses beyond 200 mcg/kg/min are not recommended," labeling states. In comparison to propranolol, the insert says "hypotension was about three times as frequent with Brevibloc, 53% vs. 17%." The reaction was "rapidly reversible" with decreased infusion rate or discontinuation of therapy and was reported less frequently in patients receiving concomitant digoxin, labeling states.