U.S. FDA Releases Long-Awaited Opioid-REMS

At a press conference on April 19, 2011, the United States government unveiled a multi-agency, multi-pronged master plan aimed at stemming the “nationwide epidemic” of prescription drug abuse. Part of the plan was the long-awaited FDA-backed Risk Evaluation and Mitigation Strategy, or REMS, focusing on reducing the misprescribing, misuse, and abuse of opioid analgesics. However, there are many facets of the Opioid-REMS to be developed during the months ahead.

Gil Kerlikowske, director of the White House Office of National Drug Control Policy (ONDCP), said the new plan — a collaborative effort involving agencies of the departments of Justice (DEA), Health and Human Services (FDA), Veterans Affairs, Defense, and others — provides a national framework for reducing prescription drug abuse and the diversion of prescription drugs for recreational use. Four key elements of the plan include:

1. Expansion of state-based prescription drug monitoring programs (while recognizing that “more work needs to be done to maximize their effectiveness”).
2. Recommending convenient and environmentally responsible ways to remove unused medications from homes.
3. Reducing the number of “pill mills” and rampant doctor-shopping through law enforcement efforts.
4. Supporting education for health care providers and patients, particularly regarding controlled substances and especially opioid analgesics.

The ONDCP’s master plan — titled “Epidemic: Responding to America’s Prescription Drug Abuse Crisis” [PDF available here] — expands upon the Obama administration’s National Drug Control Strategy.

FDA Acts to Reduce Potential Harm from Opioid Analgesics

In concert with the White House master plan, the Food and Drug Administration (FDA) announced their new REMS that will apply to all extended-release and long-acting opioid medications. Further information was provided during a separate FDA teleconference on April 20th.

A first part of the Opioid-REMS program focuses on educating prescribers about proper pain management, patient selection and monitoring, and other aspects of opioid analgesic safety.

Second, the new REMS requires prescribers to improve patient awareness about how to use these drugs safely. To achieve this, the FDA wants opioid manufacturers to develop and make available patient education materials for use at the point-of-care, as well as Medication Guides to be distributed by prescribers (voluntarily) and with each product at pharmacies (as mandated by regulation), using consumer friendly language to explain its safe use, storage, and disposal.

The opioid analgesics included under the REMS include Dolophine (methadone tablets and liquids); MS Contin, Kadian , Avinza, Embeda, and Oramorph — all of them morphines; OxyContin (oxycodone); Exalgo (hydromorphone); Duragesic (transdermal fentanyl); Butrans (transdermal buprenorphine); Opana ER (oxymorphone); and, any generic equivalents. [See official list at FDA site here.]

According to FDA Commissioner Margaret A. Hamburg, MD, the agency is stressing that a single, shared system should be used to develop and implement the REMS for all involved drugs. Opioid manufacturers will need to work together in funding and developing the patient and healthcare-provider education programs, and the contents must be approved by the FDA to ensure the materials are free of commercial influence. However, prescriber education will expectedly be offered and conducted by accredited, independent continuing medical education providers, at no cost to participants.

Opioid prescriber participation in the education and training is voluntary under the new REMS plan. However, the FDA is requiring that manufacturers monitor progress to determine if prescribers are participating in the education and if the REMS is helping to reduce problems associated with long-acting and extended-release opioids.

Manufacturers have roughly 3 months to respond to the FDA with their specific Opioid-REMS plans, and all risk-reduction measures and education are expected to be implemented during early 2012. More information and access to related documents is available at the FDA website [here].

COMMENTARY: In most respects, the FDA’s Opioid-REMS is less egregious than many feared, and the requirements seem reasonable; although some aspects seem rather broadly or vaguely defined. We have previously documented events and concerns leading up to this newly announced REMS: see UPDATES published on [10/24/2009], [12/6/2009], [7/24/2010], and [8/12/2010].

Unlike what was once dreaded as a possibility, there is no preregistration requirement for prescribers, patients, or pharmacies to participate in the new REMS. And, the specific contents of educational components are left rather open-ended by the FDA, except for a general outline, and participation in educational activities is voluntary rather than being mandated or rigidly enforced — at least presently. Here are some further observations…

• The amount of time required of prescribers to voluntarily participate in an education/training program is not specified in the REMS, nor is there a requirement that it be via a live presentation. This seems to suggest that the training might consist of self-study materials in printed form or on the Internet.
• While acknowledging that mandatory prescriber education on opioids tied to Drug Enforcement Administration (DEA) registration — which eligible professionals must have to prescribe controlled substances — would require Congressional approval, Kerlikowske seemed confident in his remarks at the press conference that it is only a matter of time before that does happen. (According to the FDA’s Janet Woodcock, MD, during the teleconference, prescribers who already received the voluntary training under REMS would most likely be “grandfathered-in” and exempt from additional requirements by the DEA.)
• It was thought, following recommendations of the FDA’s Advisory Committee last July, that ALL opioid analgesics might be included in the REMS. However, the FDA believes that long-acting and extended release formulations carry special risks and, thereby, are the only ones requiring added education and precautions, for now.
• While the REMS mentions the use of “Patient Treatment Agreements” — sometimes called Opioid Treatment Agreements or Contracts [previously discussed here] — the contents are unspecified, their use is voluntary rather than mandated by REMS, and there is no indication if they are to also include a patient Informed Consent for Opioid Treatment, which could be an essential component for safety [as discussed here].
• The FDA seems to place much importance on Medication Guides distributed with individual opioid products; however, prior research has shown such documents to be of limited value in educating patients [discussed here]. So, it is not known what might be new and improved about this element of the REMS that will enhance their effectiveness and impact. Woodcock noted that the FDA would like to see a brief (1-page) standardized format, stressing both risks and benefits, and having validated effectiveness.
• During the ONDCP press conference Q&A portion, a representative of the Drug Policy Alliance asked if the government had considered in their plans making naloxone, an opioid overdose antidote, more widely available to the public. The FDA’s Hamburg stated that they know of naloxone but have no specific plans to incorporate its use in helping to prevent overdose fatalities. We have previously written about the merits of intranasal naloxone as a lifesaving measure [here].

An essential part of the Opioid-REMS will be patient education and the enlistment of their cooperation in properly using, safeguarding, and disposing of opioid medications. To that end, we have already developed our Opioids911-Safety program [see: http://opioids911.org] with the REMS in mind, and it is freely available to healthcare providers, patients, and patients’ family caregivers.

This Internet-based program provides an understanding of opioid analgesics and their various risks, and suggests specific actions for preventing opioid-related problems. Perhaps most important, instruction is provided on recognizing opioid problems if they do occur — such as, overmedication or overdose — and on being prepared for what to do during an emergency.

Woodcock observed that prescriber education under REMS should not be burdensome, as healthcare providers already are required to participate in continuing education as a part of ongoing licensure. Furthermore, she noted, the Opioid-REMS may benefit patients, since practitioners will have a better understanding of how long-acting and extended-release opioids work, who they can help the most, and will feel more comfortable prescribing them appropriately for patients in need.

In sum, announcement of ONDCP’s master plan and the FDA’s Opioid-REMS is a clear call to action. At the present time, the FDA’s requirements seem reasonable and achievable. However, time will tell if they can have an impact on problems of opioid misuse, abuse, and overdose, while maintaining necessary access to these vital medications for patients with pain.