WYETH-AYERST's DALGAN (DEZOCINE) RECOMMENDED FOR SCHEDULE V AND NON-NARCOTIC STATUS UNDER CONTROLLED SUBSTANCES ACT -- FDA ADVISORY CMTE.

Wyeth-Ayerst's injectable analgesic Dalgan (dezocine) should be placed in Schedule V of the Controlled Substances Act based on studies of the drug's abuse potential in animals, FDA's Drug Abuse Advisory Committee recommended on Aug. 7. Although the advisory committee eventually voted unanimously to recommend that, if scheduled, the agonist/antagonist opioid analgesic should be placed in Schedule V once approved, the committee split in an earlier vote on whether to schedule the drug at all. Two of the committee members felt the drug should not be scheduled prior to marketing. The committee also unanimously recommended that dezocine not be classified as a narcotic. An NDA for Dalgan has been pending at FDA since 1983. FDAer Michael Klein, PhD, told the advisory committee that the approval of Dalgan is "imminent." Donald Jasinski, MD, Francis Scott Key Medical Center, who presented data for Wyeth-Ayerst, noted that dezocine acts like a partial agonist of morphine receptors in animals, but also shows the characteristics of a morphine receptor antagonist. "We concluded [that dezocine has] potential to abuse," Jasinski said. However, he noted that dezocine, because of its lack of toxicity and relatively low abuse potential, was safer than full morphine agonists. He maintained that dezocine did not represent "a public health problem," in part, because it would be marketed as an injectable. Wyeth-Ayerst's position was that "the injectable of dezocine not be controlled as with nalbuphine and butorphanol." Once approved, Dalgan will be the fifth agonist/antagonist analgesic to reach the U.S. market. To date, two of the agonist/antagonist analgesics have been listed as controlled substances -- oral pentazocine (Sterling's Talwin) and buprenorphine (Norwich-Eaton's Buprenex) -- by both the U.S. and the World Health Organization. Nalbuphine (DuPont's (ITALICS)Nubain) and butorphanol (Bristol-Myers' Stadol), both injectables, have not been scheduled. In addition to specifically considering Dalgan scheduling, the advisory committee was also asked by FDA to take up the question of a class approach to scheduling for agonist/antagonist analgesics. Although the committee did not vote on the question, it concurred with FDA's current position, established by then-Bureau of Drugs Director Richard Kraut and outlined by Klein in his presentation to the panel: "1) that each drug and market class will be considered under its own merits for control scheduling; and 2) for newly approved drugs where FDA has no marketing or epidemiological data on which to judge the extent of actual abuse, FDA would rather recommend a low schedule of control rather than no scheduling at all." On Aug. 8, the committee was asked by FDA for advice on developing clinical guidelines for drugs to treat abuse and for drugs with abuse potential. However, the committee, generally, was not in favor of firm guidelines for such studies. The committee, at the request of Anti-inflammatory/analgesia/anesthetic Division Director John Harter, said it would be willing to meet more often -- up three-to-four times a year -- to discuss specific problems as they come up. Before the Aug. 7-8 meeting, FDA's Drug Abuse Advisory Committee had not met since January 1985. At that time, the committee was under the authority of FDA's Neuropharmacologic Drugs Division. Drug abuse functions have since been switched to pilot review staff in the Anti-inflammatory/analgesia/anesthetic Division.