Executive Summary

ANAQUEST FORANE LABELING: VASODILATION ACTION should be included in labeling of the anesthetic agent, FDA's Anesthetic & Life Support Drugs Advisory Committee recommended at its Aug. 29 meeting. The group also recommended including statements that "coronary steal" (the diversion of blood flow from the myocardium) has been seen in animal models, but has not been conclusively shown in humans, and that evidence relating vasodilation to coronary steal and ischemia is inconclusive. The committee met to discuss labeling changes proposed by Anaquest. The Madison, Wisc.-based firm had proposed adding a discussion of the drug's vasodilation effects to the "Clinical Pharmacology" section of labeling. The firm also suggested including a statement that vasodilation can cause coronary steal. Anaquest suggested adding that with proper hemodynamic monitoring isoflurane can be safely used in patients with coronary artery disease. The firm further proposed including an indirect reference to ischemia, which would state: "Control of patient hemodynamics . . . is the most critical factor in preventing perioperative myocardial ischemia in patients with coronary artery disease." The committee initially voted against the proposed reference to ischemia, asserting that the statement was not specific to the drug. After presentations from FDA-invited speakers on current literature regarding the link between vasodilation and ischemia, the committee concluded that Forane labeling should note that some evidence, although inconclusive, supports the association. In a separate review, the committee recommended approval of Anaquest's Enlon Plus (edrophonium chloride, 10 mg per ml and atropine sulfate, 0.14 mg per ml), a pre-mixed combination of the two approved agents. Atropine, an anti-muscarinic, is frequently administered with edrophonium (Enlon) to counter its muscarinic (heart slowing) effect. The committee suggested a precautionary statement on the monitoring of heart rate be included in the package insert for Enlon Plus. Because atropine may initially slow the heart on administration, the committee recommended a statement cautioning physicians to evaluate initial heart rate before administration and to make preparations to manage the heart rate should slowing occur.