REMS programs are meant to focus on drugs that are associated with special risks that the FDA does not feel are sufficiently addressed by the standard prescribing information.
For the past 2 years, the FDA has struggled to design an appropriate risk evaluation and mitigation strategy (REMS) program for opioid analgesics. During that period, there were several proposals for such a program, but none was adopted until April 2011, when a program was finally announced.1,2 Although some of the details of the program still remain to be worked out, there is sufficient information to reasonably determine what the final program will look like.
The requirement for the FDA to develop REMS programs became law in 2007, and since then they have been issued for several drugs. REMS programs are meant to focus on drugs that are associated with special risks that the FDA does not feel are sufficiently addressed by the standard prescribing information. There is no single REMS program that applies to all drugs; each drug or class of drugs is addressed according to the special circumstances associated with its use.
The development of an REMS for opioids has probably been the most widely publicized and controversial of all the programs because of the growing problem of prescription drug abuse in the United States. The FDA did state that its goal is not only to reduce harmful behaviors but also to improve pain management.1
What is in the REMS program for opioids? First of all, the only opioids it currently addresses are long-acting and extended-release opioid products. These include extended-release oxycodone (both OxyContin and generic forms), transdermal fentanyl (Duragesic and generics), extended-release forms of morphine (MS Contin, Avinza, Kadian, Oramorph, and generics) and hydromorphone (Exalgo), transdermal buprenorphine (Butrans), and methadone. Curiously, the other pharmacologically long-acting opioid, levorphanol (Levo-Dromoran), is not in the initial list.3
Earlier proposals for an REMS program addressed both short- and long-acting formulations. That the current proposal seems to be a compromise to avoid appearing too onerous for prescribers is indicated by the fact that prescriptions for extended-release and long-acting opioids are only a small minority of the total number of opioid prescriptions written in the United States. According to the FDA, in 2009 there were 23 million prescriptions for the extended-release and long-acting opioids and 257 million for all opioids.1 Hydrocodone (the opioid in Vicodin), which is one of the most commonly prescribed and, as a result, also one of the most frequently abused of all the prescription opioids, is not included in the program because it does not have an extended-release formulation.4
Under the REMS program, drug manufacturers will be required to develop training programs for health care professionals that discuss a variety of topics, including patient selection, initiation of therapy, assessment of the risk for abuse, patient monitoring for misuse or abuse, and patient counseling for the appropriate use of the drugs and the risks involved in their use.3 Once the manufacturers develop these programs, they will be reviewed by the FDA for approval. The FDA expects that the training programs will be funded by unrestricted grants from the manufacturers and will be administered by Continuing Medical Education providers.
One can only wonder why the APA has demonstrated so little interest in involving psychiatry in pain management.
Under the REMS proposal, participation in the educational programs by prescribers would be voluntary. However, at virtually the same time that the FDA issued the REMS program, President Obama’s administration said that it would seek legislation that would require specific training in opioid prescribing for all practitioners who want Drug Enforcement Administration (DEA) registration to prescribe controlled substances.5 The administration’s statement also contains recommendations for improving overall teaching of pain management and substance abuse in health care professional schools, increasing research on prescription drug abuse, and improving enforcement of laws to address those prescribers who are supplying opioid prescriptions for illegitimate purposes.
Will the REMS program result in a significant improvement in how physicians’ prescribe the listed opioids? Will it reduce their abuse and misuse and result in better management of pain? I wish I could be more optimistic, but I doubt that it will unless the administration’s proposal for required education is also adopted.
For those few health care professionals who are prescribing these drugs primarily for illegitimate reasons and who care little about the people for whom they are providing them or the negative impact on society in general, the program will obviously do little to inhibit their activity. As for health care professionals who believe they are prescribing them for legitimate medical reasons, most probably believe that they are doing so appropriately; they therefore would see little reason for additional training on the drugs they are already prescribing.
Probably nothing will change the behavior of the first group apart from frequent prosecution of miscreants. The second group may benefit; with better understanding of these drugs, patient care will improve. I believe it is imperative that, as the administration proposes, education be a prerequisite to DEA registration.
The opioid REMS program is expected to be implemented by the beginning of 2012. In future columns, I will discuss developments as the specific items in the program are firmed up.
I will close with a comment about a press release issued by the American Psychiatric Association (APA) applauding the REMS program and the administration’s recommendations. In it is a statement by John Renner, MD, chair of the APA Council on Addiction Psychiatry: “It is important for all clinicians to recognize that we share a major professional responsibility to ensure that prescriptions for opioids and other abuseable medications are prescribed only for appropriate indications.”6
If the APA considers this to be of such great importance, one can only wonder why it has demonstrated so little interest in involving psychiatry in pain management. As readers of one of my previous columns are aware, the proposals for DSM-5 recommend reducing psychiatry’s already limited involvement in pain and continue to fail to recognize the significant problem of iatrogenic substance abuse. I hope that the APA will recognize that its failure to actively support making pain management an important part of psychiatry has had a detrimental effect on the care of patients for whose well-being it expresses concern.
1. US Food and Drug Administration. Opioid Drugs and Risk Evaluation and Mitigation Strategies (REMS). http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugclass/ucm163647.htm. Accessed June 3, 2011.
2. Barlas S. Washington Report: Obama drug misuse strategy targets physician education. Psychiatr Times.2011;28(6):32.
3. US Food and Drug Administration. Information by Drug Class. http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/default.htm. Accessed June 3, 2011.
4. Centers for Disease Control and Prevention. Emergency department visits involving nonmedical use of selected opioid prescription drugs-United States, 2004-2008. MMWR.2010;59:705-709.
5. Executive Office of the President. Epidemic: responding to America’s prescription drug abuse crisis. Washington, DC; April 2011.
6. American Psychiatric Association. APA, AAAP, and AOAAM applaud federal action combating prescription drug abuse. Release No. 11-23; April 21, 2011. http://www.psych.org/MainMenu/Newsroom/NewsReleases/2011-News-Releases_1/Combating-Prescription-Drug-Abuse-.aspx?FT=.pdf. Accessed June 9, 2011.