Following the Food and Drug Administration (FDA) announcement in April 2011 that manufacturers of certain opioids would have to consult to formulate a class-wide Risk Evaluation and Mitigation Strategy (REMS) for long-acting opioids (LAOs) and extended-release (ER) opioids, we asked our panel of experts for their opinions and comments on the current situation relating to opioid REMS. Their responses are shown below.
Details of class-wide REMS are still being developed
"Although the FDA made its formal announcement in April 2011 regarding the requirement for a class-wide Risk Evaluation and Mitigation Strategy for long-acting opioids and extended-release opioids, it is a time to be reminded that details are still being developed among the FDA, American Academy of Continuing Medical Education, and the Industry Working Group."
Perry Fine, MD, University of Utah, Salt Lake City, UT
FDA expects producers of class-wide LAOs/ER opioids to work together
"The goal of REMS for opioids is to reduce the risk of inappropriate prescribing, accidental use by children, and to minimize deaths associated with these drugs.
The FDA recently announced that manufacturers of LAOs and ER opioids – such as morphine and Duragesic – are required to have a REMS that makes educational materials available for prescribers (weighing the risks and benefits of opioid therapy, choosing patients appropriately, managing and monitoring patients) and for patients (safe use and storage of these drugs).
FDA expects manufacturers of the class of long-acting and extended-release opioids to work together to provide the educational materials as part of a class-wide single shared system.
It will take several months to develop these educational materials. In the meantime, healthcare professionals may continue to prescribe LAOs and ER opioids as usual. However, all prescribers are encouraged to thoroughly discuss the risks and benefits of these products with their patients."
Michael J Brennan, MD, The Pain Center of Fairfield, Fairfield, CT
Patients and prescribers will actively seek REMS-friendly pharmacies
"The REMS provisions of the Food and Drug Administration Amendments Act (FDAAA) of 2007 are the latest regulatory challenge and opportunity for pharmacists. Just as other regulatory challenges have turned into opportunities for some pharmacists, REMS can be a vehicle for promoting expanded involvement of pharmacists in patient care.
Pharmacists are positioned at a critical point in drug distribution where they can assure that the risk minimization strategies of the REMS program are effective without being unduly burdensome.
REMS compliance will eventually lead to a specialty practice in pharmacy, just as the OBRA-87 legislation has led to pharmacists specializing in long-term care, and the Medication Therapy Management legislation has led to specialty pharmacy practice focusing on the monitoring and management of drug therapy. Specialty pharmacy practice is not the same as restricted distribution to a specific pharmacy.
Any pharmacy may develop a specialty in particular classes of medications such as opioid analgesics. These pharmacies are likely to become identified as "REMS-friendly" pharmacies.
Patients are likely to experience a higher level of care, and perhaps higher satisfaction, when their prescriptions are filled at a specialty pharmacy. There is no question that REMS present obstacles to the care of patients, and that these obstacles are purposeful.
The whole point of REMS is to assure that risks are minimized and that benefits are maximized. The system of drug distribution will be impeded by REMS when situations arise in which the risk–benefit balance is tipped in a direction that does not serve the patient well. Pharmacists will often find that they have an opportunity to reset that balance so that it tips in favor of patient safety. This can be done through:
- provision of information directed to the patient
- monitoring of therapy to assure that prescribers are authorized to prescribe
- ensuring that patients are authorized to use a medication with a serious risk
- coaching of prescribers and patients on the purpose of REMS and the approach that can be taken to comply with requirements imposed by the program.
Pharmacists will share with prescribers the responsibility for assuring that the less restrictive REMS programs currently envisioned by FDA are successful, obviating the necessity to impose additional and more onerous restrictions.
Many pharmacists will welcome the chance to become involved in the care of patients whose medications are subject to REMS. They will seek out the problematic circumstances that others avoid."
David Brushwood, RPh, JD, University of Florida, Gainesville, FL
The FDA can only partially resolve the problem
"Getting ready for REMS has proven to be more uncertain than was initially expected. When the FDA was newly empowered by the FDAAA of 2007, it was initially felt that REMS were going to be sweeping and involve not just increased education but also perhaps – amongst the elements to assure safe use – extensive procedural changes in the actual prescribing of LAO pain medications. Indeed, on considering that FDA has the unenviable task of addressing the risks of opioids fairly without also limiting their use and potential benefits, it is not surprising that there have been changes to the form that opioid REMS will take.
FDA should be applauded for their efforts in seeking expert and public opinion and spending time trying to get it right, even if that has meant delays and changes in direction.
Balancing the significant public health problems of pain and prescription opioid misuse, abuse and overdose is not simple and cannot be done solely with posturing and sound bites. In the end,
a major, multi-agency response is required, as FDA with its particular mission and jurisdiction can only partially resolve the problem.
That said, it seems that when the major risks of opioids, misuse, abuse, and overdose are considered, the scope of what REMS can reasonably be expected to address varies for each, and even more so when it is considered that risks extend beyond persons to whom opioids are actually prescribed.
Misuse and abuse by pain patients can be addressed with education to some extent and overdose in pain patients to an even greater extent. Overdose in non-pain patients will require more novel approaches above and beyond the education mentioned to include such public health initiatives as Project Lazarus that supplies naloxone to be used as rescue in overdose settings.
How can the office be made ready? In regard to the required education this is not difficult – practitioners do it all the time when it comes to continuing medical education. But:
What will require thought is how the lessons learned are utilized in practice, particularly in respect to discussion of risk stratification, tailoring of delivery of opioid therapy to correspond to the assessed level of risk, and inclusion of more patient education and management of overdose risk.
This may require incorporation of tools, monitoring, and consultations that will actually provide the more complex pain patients with a pain plan that does them justice. The delivery of opioid therapy following best practices will become a more individualized, time-consuming, and complex affair in some cases, as it should be.
FDA has made a considerable effort to ensure that what constitutes REMS are not instigated hastily, nor has it played one public health crisis off against another. To adopt best practices and put the education into play, practitioners will have to be ready to do the same."
Steve Passik, PhD, Vanderbilt University Medical Center, Nashville, TN
REMS will soon become the new routine for prescribing of opioids
"In April 2011, the FDA announced a need for class-wide REMS for LAOs and ER opioid analgesics. REMS are already instituted for transmucosal immediate-release fentanyl (TIRF) products, also known as rapid-onset opioids. Several steps can be implemented in nurse practitioner practices to meet the challenges inherent in REMS. These will need a systematic approach to ensuring that requirements are not only met, but documented appropriately.
The areas that will affect nurse practitioners most are: (i) nurse practitioner education, (ii) appropriate patient selection, and (iii) patient/family education. Nurse practitioners must first learn about REMS. Existing literature on implementing REMS in practice is sparse since much is still at the developmental stage. The pharmaceutical industry will provide material regarding safety, efficacy, and appropriate selection. This and other materials for FDA-approved REMS will supplement what already exists regarding state and federal regulations for opioid prescribing. Web sites such as Ready For REMS provide valuable and current information.
Nurse practitioners need to develop a system to document that they are compliant with this educational requirement; implementing a log of relevant education will facilitate this practice.
Patient education must include indications and safety concerns for opioid analgesics. Documentation should include a signed informed consent, opioid analgesic use agreement, and any drug or drug-class-specific REMS.
Additional REMS requirements are likely to impact current standard operating procedures in practice, and this will soon become the new routine for the prescribing of opioid analgesics.
The purpose of REMS is to facilitate good practice and documentation, improve communication with patients, decrease abuse and diversion of these medications, and improve access for appropriate patients."
Patricia Bruckenthal, PhD, RN, ANP-C, Stony Brook University School of Nursing, Stony Brook, NY
Working collectively towards safe use of all opioids
"The FDA-imposed REMS for LAOs and ER opioids will soon be enshrined in law. The purpose of REMS is to force industry to take more responsibility for safe prescribing and use of opioids. It is undeniable that opioids have been associated with a dramatic rise in abuse and overdose deaths during the past 15 years. Yet, the recent Institute of Medicine report reveals the concurrent problem of shameful inattention to chronic pain treatment for millions of Americans.
Few providers can avoid facing the two public health issues of opioid-related harm and impeded access to effective pain therapies.
It is important to keep in mind that providers, industry, government, and patients share a common goal, namely the safe use of all medical therapies.
The intention of REMS to collectively work towards safe use of all opioids, not just LAO/ER opioid formulations, should be embraced.
There should also be continued advocacy for access to appropriate treatment for all patients suffering from pain. This could be a transformational opportunity for our specialty and the medical profession."
Lynn Webster, MD, Lifetree Clinical Research and Pain Clinic, Salt Lake City, UT
Practical tips for pharmacists
"The FDA announced plans in April 2011 for a class-wide REMS for LAOs and ER opioids. This requires manufacturers of these opioid analgesics to disseminate education programs to prescribers on proper pain management, and to help patients know how to use these drugs safely. The following week, the Office of National Drug Control Policy (ONDCP) released a plan for education, monitoring, proper disposal, and enforcement, to reduce prescription drug abuse.
All LAO/ER opioids will be required to have a REMS.
Specifically, the products are: Dolophine (methadone), MS Contin, Kadian, Avinza, Embeda, Oramorph (all morphines), OxyContin (oxycodone), Exalgo (hydromorphone), Duragesic (transdermal fentanyl), Butrans (transdermal buprenorphine), and Opana ER (oxymorphone). See also the following FDA Web site page:
http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm251735.htm
What can pharmacists do now to prepare for LAO/ER opioid REMS?
- Pharmacists should stay up-to-date on the new program as manufacturers implement their prescriber education programs and develop patient information, including Medication Guides for the products that become available. The ReadyForREMS Web site provides updates on this issue soon after they become available.
- Pharmacists should also review their operating procedures for dispensing of LAO and ER opioids:
- Are procedures adequate for ensuring that a Medication Guide is dispensed with each LAO and ER opioid prescription?
- How are Medication Guides managed in the pharmacy practice?
- Review staff roles, train staff, and monitor their performance. Ensure that they know which products require Medication Guide distribution, particularly those for LAOs which will impact a large number of prescriptions compared with other REMS programs.
- Increase communication with your patients. The ReadyForREMS Web site has a useful guide for patients on LAOs and REMS. It would appropriate to start the conversation about safe use, prior to Medication Guide requirements, and reinforce the prescriber’s education on appropriate use.
- Stay tuned on the safe storage and disposal of opioid medications.Ensure that you know the federal and state regulations for disposal and participate in national “take back” programs and provide information on these initiatives to patients. The next National Take Back Initiative is on October 29, 2011, 10:00–14:00."
Marsha K Millonig, MBA, RPh, Catalyst Enterprises, LLC, Eagan, MN