FDA Approves REMS for Extended-Release, Long-Acting Opioids

Susan Jeffrey

July 09, 2012

July 9, 2012 — The US Food and Drug Administration (FDA) has approved a new Risk Evaluation and Mitigation Strategy (REMS) for extended-release (ER) and long-acting (LA) opioid analgesics in the treatment of moderate to severe chronic pain.

The centerpiece of the plan is education for prescribers through a requirement of more than 20 opioid manufacturers to provide continuing education programs on proper use of these drugs, said Margaret Hamburg, MD, commissioner of the FDA, during a press conference today.

"Specifically, the REMS requires companies to make continuing education programs available for prescribers based on a blueprint developed by the FDA that specifies the content of the training," Dr. Hamburg said.

Continuing education will include information on how to weigh the risks and benefits of opioid therapy, she added, "and how to recognize evidence of and potential for opioid misuse, abuse, and addiction." The education will be funded through grants from the manufacturers to continuing medical education providers, who will develop and deliver the training.

Companies must also produce FDA-approved patient education materials to ensure that the drugs are taken safely, and to explain how to safely store and dispose of these drugs, she noted.

"Our action today is part of a multiagency federal initiative led by the White House Office of National Drug Control Policy and builds upon the Obama administration's 2011 Prescription Drug Abuse Prevention Plan," Dr. Hamburg said. That plan rests on 4 strategies to reduce prescription drug abuse, including education, monitoring, proper medication disposal, and enforcement.

At the press conference, Gil Kerlikowske, director of the Office of National Drug Control Policy, said the Obama administration has been "laser-focused" on this issue but recognizes that they have to "strike a balance between our work to minimize the abuse of prescription drugs and the need to ensure access to their pivotal use in treating pain."

To date though, the education is mandatory for manufacturers but still elective for prescribers. Kerlikowske said work will be undertaken to change that.

"As this initiative moves forward, we will continue to work with Congress and members of both parties to ensure that prescriber education is not just voluntary, but is a prerequisite for those who prescribe prescription drugs," he said.

Other actions have included programs like the Drug Enforcement Administration (DEA) National Take-Back Day, on which patients can turn in unused opioid medications, supporting law enforcement work to shut down so-called "pill mills," and expanding tracking of prescriptions through state-based databases that are now in place in all states with the exception of Missouri, he said.

The FDA expects that at least 60% of the current number of 320,000 prescribers of EL/LA opioids will have received the training by the third year of the program, Dr. Hamburg said.

"We would of course like to see the number even higher in terms of the training received, and, as Director Kerlikowske mentioned, we are still working with Congress to explore a way of mandating our training as part of DEA registration."

The issue has been the difficulty involved in striking a balance between addressing the problem and not burdening providers or interfering with access to pain medication, Dr. Hamburg noted. "But I do believe that we can provide a very focused and effective educational program that doesn't take a lot of time but will benefit physicians in their practices, and will benefit patients and ultimately will benefit public health."

Single Shared REMS

John Jenkins, MD, director, from the Office of New Drugs of the Center for Drug Evaluation and Research, FDA, said the agency encouraged manufacturers to work with them to develop a single shared system REMS.

"The manufacturers formed a group called the REMS Program Committee, or RPC, and they worked closely with FDA on development of the REMS," Dr. Jenkins said. The REMS requires companies to make continuing education available to all DEA-registered prescribers of EL/LA opioids at no or nominal cost, based on the FDA blueprint.

"The RPC has set up a structure for funding these educational grants and will support the work of the continuing education providers with a website and a call center," Dr. Jenkins added. "However, let me emphasize that the companies are not permitted to be involved in the actual course design or curriculum. The FDA blueprint contains the core educational messages for the prescriber training and specifies proper prescribing practices for physicians, nurse practitioners, and physician assistants."

The agency will monitor company reports of the number of educational grants awarded, the number of prescribers trained, and other relevant information. "If FDA determines that the REMS is not meeting its goals, the agency will re-evaluate the program," he said. The first course is expected to be available no later than March 1, 2013.

It will also include a knowledge assessment and proof of completion of the program for prescribers. In addition, Dr. Jenkins noted, "the continuing education courses will be subject to an independent third-party audit to ensure that their content and messages conform to the FDA blueprint and are free of commercial influence."

Finally, Dr. Jenkins noted, "Follow-up surveys will be conducted to assess prescriber understanding of the important safety information and to assess whether the REMS is adversely affecting patient access to necessary pain medications."

Drugs that will be required to have an REMS in place include the following:

  • Avinza

  • Butrans (transdermal buprenorphine)

  • Dolophine (methadone)

  • Duragesic (transdermal fentanyl)

  • Embeda

  • Exalgo (hydromorphone)

  • Kadian

  • MS Contin

  • Opana ER (oxymorphone)

  • Oramorph (all morphines)

  • OxyContin (oxycodone)

The American Pain Society issued a response to the new REMS July 11, saying that the move "is consistent with the American Pain Society's strong belief that competency-based educational programs will benefit both primary care and specialty prescribers of ER/LA opioids and ultimately improve patient safety and decrease diversion, while still assuring access to these medications for patients who need them."

Professional and consumer education can help improve awareness and reduce behaviors that contribute to opioid abuse, the APS statement notes. "For example, the FDA's mandate that simplified medication guides and information sheets for ER/LA opioids be made available for patients will hopefully lead to improved knowledge concerning proper use, storage, and disposal of these drugs and result in less intentional and unintentional diversion of these medicines."

The mandated education for prescribers and dispensers should be offered through a variety of channels, the APS response notes. "APS and other professional societies can play a vital role in helping develop educational modules as part of the REMS programs implemented by FDA and drug manufacturers." Training for clinicians should be "evidence based, and designed to develop and improve clinical skills such as patient assessment, communication and recognition of risks for abuse as the basis for developing integrated treatment plans, revising treatment plans, and making referrals to pain specialists as necessary." However, the statement does note some concern. "Despite our appreciation for the ER/LA REMS as announced, APS continues to disagree with FDA's decision to limit REMS to extended-release, long-acting opioids only. All opioids must be used, stored, and disposed of in similar ways for maximum safety."

In a statement of its own issued July 9, the American Academy of Pain Medicine (AAPM) similarly applauded the FDA's REMS, calling it a "huge leap forward."

"We are pleased to have worked with FDA and other groups in the development of this REMS," the AAPM statement notes. "As a leading provider of continuing medical education in this field, we know that increased education and training of practitioners and patients can reduce adverse outcomes that are often associated with opioids."

Proper education and training mean that opioids can be administered safely and remain an important option for the treatment of chronic and debilitating pain, the AAPM points out. "We will also shortly be issuing a series of best practices for both patients and prescribers that we believe can further reduce adverse outcomes associated with opioids."

Their Safe Opioid Prescribing Course has already been offered to hundreds of physicians practicing pain medicine, the statement concludes. "We believe that it can serve as a model for the continuing medical education programs required by the REMS and look forward to providing our expertise in partnering with FDA and others in the field to ensure that prescribers receive the most effective education and training possible."

An estimated 22.9 million prescriptions for extended-release or long-acting opioids were dispensed in 2011, Dr. Hamburg said.

According to numbers from the Centers for Disease Control and Prevention, deaths due to unintended consequences of opioid medications are increasing, rising from approximately 15,000 to 16,000 between 2008 and 2009.


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