Welcome from Michael J. Brennan, MD, and Jeffrey Gudin, MD
Opioid overdose is a major public health problem, accounting for almost 17,000 deaths per year in the United States.1 Overdose occurs in both males and females of all ages, ethnicities, and demographics, and involves both illicit opioids such as heroin and, increasingly, prescription opioid analgesics such as oxycodone, hydrocodone, fentanyl, and methadone.2
Physicians and other health care providers can reduce the risk of opioid adverse effects with thoughtful prescribing and monitoring of patient responses. Clinicians need a thorough understanding of the inherent pharmacologic properties of a particular opioid analgesic, and to recognize the nuances of each formulation or delivery system (ie, controlled release, immediate release, or rapid onset) they prescribe. Care needs to be taken when prescribing these agents concomitantly with other central nervous system depressants, and a “Universal Precautions” approach has been recommended for all patients being considered for chronic opioid therapy.3
Some of these precautions include psychological screening, urine (or other matrix) toxicology testing, prescription drug monitoring database programs, informed consent, and ongoing risk assessment. In 2012, the FDA approved a Risk Evaluation and Mitigation Strategy (REMS), which introduced new safety measures to reduce risks and improve the safe use of extended-release/long-acting opioids while continuing to provide access to these medications for patients in pain.
The Substance Abuse and Mental Health Services Administration recognizes that healthcare practitioners, communities, workplaces, patients, and families all can contribute to preventing prescription drug abuse, and in 2014 released an Opioid Overdose Prevention Toolkit that described strategies to prevent opioid overdose for all of these groups.
Academic researchers and pharmaceutical companies also have taken ownership and a stake in the prevention of abuse, misuse, diversion, and overdose of prescription opioids. “While prescription opioids are an important component of pain management, abuse and misuse of these products have resulted in too many injuries and deaths across the United States,” said Douglas Throckmorton, MD, Deputy Director for Regulatory Programs in the U.S. Food and Drug Administration’s (FDA’s) Center for Drug Evaluation and Research. “An important step towards the goal of creating safer opioids is the development of products that are specifically formulated to deter abuse.”4
To combat opioid misuse and abuse, the FDA is encouraging manufacturers to develop abuse-deterrent drugs that work correctly when taken as prescribed, and are formulated in such a way that deters misuse and abuse, including making it difficult to snort or inject the drug for a more intense high. While drugs with abuse-deterrent properties are not “abuse-proof,” the FDA sees this guidance as an important step toward balancing appropriate access to opioids for patients with pain with the importance of reducing opioid misuse and abuse. On April 1, 2015, the FDA issued a final guidance to assist industry in developing opioid drug products with potentially abuse-deterrent properties. The document “Guidance for Industry: Abuse-Deterrent Opioids—Evaluation and Labeling” reviewed in this issue of PainScan explains the FDA’s current thinking about the studies that should be conducted to demonstrate that a given formulation has abuse-deterrent properties.5 It also makes recommendations about how those studies should be performed and evaluated, and discusses what labeling claims may be approved based on the results of those studies.
The Centers for Disease Control and Prevention has classified prescription drug abuse as an epidemic. While the use of some illegal drugs like cocaine has markedly decreased in recent years, prescription drug abuse is a growing problem. According to results from the 2009 National Survey on Drug Use and Health (NSDUH), nearly one-third of people aged 12 and older who used drugs for the first time began by using a prescription drug non-medically.6 A 2011 White House Prescription Drug Abuse Prevention Plan included action in 4 major areas to reduce prescription drug abuse: education, monitoring, proper disposal, and enforcement.7
In addition to these governmental efforts, newer abuse-deterrent and tamper-resistant pharmaceutical formulations of controlled substances have and are being developed to maintain the efficacy and improve the safety of these valuable analgesic medications. Opioids may be the only effective therapies for patients suffering with severe chronic pain.
Studies of cost-effectiveness also will be necessary in addition to studies of efficacy, safety, and abuse deterrence.8 The acceptance of newer abuse-deterrent drug formulations will require endorsement from clinicians, patients, governmental agencies and third-party payors who typically favor less expensive, non-abuse deterrent generic opioids on their formularies. In order for these agents to be widely prescribed, insurers will need to cover tamper-resistant opioids without the expected roadblocks of lengthy preauthorizations or higher copays. As more postmarketing data about the effectiveness of ADFs becomes available, insurers will be better able to calculate the pharmacoeconomic benefits of these agents in order to justify the additional upfront expense.
In this issue of PainScan, we reviewed influential studies on abuse-deterrent technologies to keep readers up to date on the progress being made in this field and the impact of these technologies on reducing the risk for opioid abuse, misuse, and overdose.
1. Chen LH, Hedegaard H, Warner M. Drug-poisoning deaths involving opioid analgesics: United States, 1999–2011. NCHS Data Brief, no. 166. Hyattsville, MD: National Center for Health Statistics. 2014.
2. Painkillers fuel growth in drug addiction. Opioid overdoses now kill more people than cocaine or heroin. Harv Ment Health Lett. 2011;27(7):4-5.
3. Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: a rational approach to the treatment of chronic pain. Pain Med. 2005;6(2):107-112.
4. U.S. Food and Drug Administration. FDA News Release: FDA issues draft guidance on abuse-deterrent opioids. January, 2013. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm334785.htm
5. U.S. Department of Health and Human Services, U.S. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Abuse-Deterrent Opioids—Evaluation and Labeling: Guidance for Industry. April 2015. Available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM334743.pdf.
6. Substance Abuse and Mental Health Services Administration. Results from the 2009 National Survey on Drug Use and Health: Volume I. Summary of National Findings. Rockville, MD: Office of Applied Studies, NSDUH Series H-38A, HHS Publication No. SMA 10-4586Findings; 2010.
7. Executive Office of the President United States of America. Epidemic: Responding to America’s Prescription Drug Abuse Crisis. 2011. Available at: https://www.whitehouse.gov/sites/default/files/ondcp/issues-content/prescription-drugs/rx_abuse_plan.pdf.
8. Romach MK, Schoedel KA, Sellers EM. Update on tamper-resistant drug formulations. Drug Alcohol Depend. 2013;130(1-3):13-23.