1. RISK EVALUATION AND MITIGATION STRATEGIES FOR LONG-ACTING OPIOID ANALGESICS REMS Katherine E. Galluzzi, D.O., CMD, FACOFP dist. Chair – AOA Council on Palliative Care Issues

2. EDUCATIONAL OBJECTIVES Acknowledge the importance of opioid analgesics for treatment of patient with moderate-to-severe pain Understand the problem of misuse/abuse/diversion in light of the increasing use of opioids as a mainstay in the armamentarium against pain Seek to strike a balance between appropriate pain control and responsible prescribing of long-acting opioid analgesics Recognize the role of risk evaluation and mitigation strategies in protecting both patient safety and access to appropriate pain medications

5. The Bottom Line on Misuse/Diversion/Abuse From the Physician’s Perspective “If a clinician has the slightest inkling that a patient presenting with severe pain has an ulterior motive for wanting pain control interventions, the clinical encounter becomes a ‘no win’ scenario from the clinician’s perspective. If he prescribes an opiate, he’ll be staring at the ceiling in the middle of the night wondering if the opiate is being sold on the street. If the clinician doesn’t prescribe an opiate, he’ll be staring at the ceiling wondering if he caused a patient to needlessly endure ongoing pain.” – Paul Grossman, MD, family physician

7. WHAT IS A REMS? REMS = Risk Evaluation and Mitigation Strategy Designed to manage a known or potential serious risk Allows appropriate patients continued access to medications Ensures benefits outweigh any potential safety risks Not driven only by addiction or abuse –there is also a need to ensure that healthcare professionals and patients are fully aware of important safety messages, such as the requirement for patients to be opioid-tolerant before they can take certain medications

8. WHY BOTHER? Because proceeding without REMS is not an option: This is going to be mandated by the FDA Reliance on products without REMS may lead to inadvertent under-treatment of pain in appropriate patients

9. THE MANDATE “We expect all companies marketing these products to work with us [to implement REMS] expeditiously. If not, we cannot guarantee that these products will remain on the market” 1 Bob A. Rappaport, MD Director Division of Anesthesia, Analgesia and Rheumatology Products Center for Drug Evaluation and Research Food & Drug Administration  Excerpt from presentation by Rappaport BA, March 3, 2009. REMS for Opioid Analgesics: How Did We Get Here? Where are We Going?  http://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyD rugClass/UCM163672.pdf. Accessed September 2009. http://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyD rugClass/UCM163672.pdf. Accessed September 2009

10. REMS in Other Therapeutic Areas Risk management programs are not new to medicine Pain medications have not been singled out There are REMS for many other medications: ProductREMS program Accutane (isotretinoin)iPLEDGE 1 Entereg (alvimopan)EASE Program 2 Nplate (romiplostim)NEXUS Program 3 1.https://www.ipledgeprogram.com/. Accessed September 2009; 2.http://www.adolor.com/research/index.asp?page=entereg- alvimopan.Accessed September 2009; 3.http://www.nplate.com/. Accessed September 2009.

12. LETS GET READY FOR REMS Opioids are effective analgesics However, nonmedical use including misuse, abuse, and diversion of opioids is increasing It is critical to maintain access to these drugs for appropriate patients As such, it is vital that healthcare providers and patients understand important opioid safety messages It’s time to do the right thing –REMS are necessary to ensure that the benefits of medications outweigh risks Minimize harm to patients REMS exist outside pain medicine, with proven success