FDA Anesthetic & Life Support Drugs Advisory Committee Sept. 10, 2003

FDA Anesthetic & Life Support Drugs Advisory Committee Sept. 10, 2003 Art Van Zee,MD St. Charles Clinic St. Charles, Va.

Susstained-release hydromorphone (Palladone) --Risks vs. benefits discussion

Benefits Review sustained release opioids vs. IR opioids

IR oxycodone vs CR oxycodone Comparable Efficacy & Safety Hale Clin J Pain 9/99 BACK PAIN Kaplan R J Clin Oncol 10/98 CANCER Stambauugh J.Clin Pharm 5/01 CANCER

OxyContin--NDA--1995 MEDICAL OFFICER REVIEW (MOR) Summary of Safety “ The best conclusion is that the efficacy of the CR (oxycodone) is equivalent to the IR, with an adverse event profile that is as good as the IR. I would not allow a ‘better’ claim” --Curtis Wright, MRO

OxyContin---NDA---1995 Summary of Efficacy “CR oxycodone appears to be a BID alternative to conventional QID oxycodone. Approval is recommended. Care should be taken to limit competitive promotion. This product has been shown to be as good as current therapy, but has not been shown to have a significant advantage beyond reduction in frequency of dosing.” --Curtis Wright, MRO

The Medical Letter—9/17/01 “OxyContin is a q12h controlled-release formulation of oxycodone that can be used effectively in the treatment of pain due to cancer, and occasionally, other types of chronic pain. There is no evidence that oxycodone offers any advantage over appropriate doses of other opioids, and it appears to have the same potential for addiction as morphine.”

CR morphine vs CR oxycodone Comparable in Efficacy and Safety Heiskanen Pain 10/97 CANCER Mucci-LoRusso ’98 CANCER Bruera J. Clin Oncol 10/98 CANCER

IR hydromorphone vs CR hydromorphone (Q12hr) Comparable Efficacy and Safety Hayes Cancer 9/94 CANCER Bruera J. Clin Oncol 5/96 CANCER

CR oxycodone vs CR hydromorphone (Q12hrs) Comparable Efficacy & Safety Hagen Cancer 4/97 CANCER

Summary 1. IR opioids and SR opioids are comparable in efficacy & safety 2. SR preparations appear comparable in efficacy & safety

Benefits: ---CONVENIENCE of bid or qd dosing ---Convenience of less pills ---for patients intolerant to other opioid preparations

Risks of sustained release • hydromorphone • of addiction when taken as • prescribed-----Unknown • of addiction—when used • non-medically—recreationally • of overdose and death—high • potency opioid dosing-- one pill

RISKS of CR hydromorphone • Brief over-view of the promotion • and marketing of OxyContin • ---”Aggressive” marketing for chronic non-malignant pain • ---Aggressive marketing to primary • care physicians

OxyContin marketing (cont) • -- Trivializing the risk of addiction for chronic • non-cancer pain • --Use of sophisticated marketing • data to target and influence • high opioid prescribing docs

% above national average 1998 2000 Counties hydrocodone OxyContin Tazewell,Va 545% 456% Perry, Ky 415% 559% Logan,WVa 397% 430%

Personal thoughts: • Replication of OxyContin problem if “Indications” for use of Palladone, and marketing---are the same as OxyContin • 2. Unrestricted use in cancer • Restricted use to a “compassionate use” program • in chronic non-cancer pain

FDA Anesthetic & Life Support Drugs Advisory Committee Sept. 10, 2003