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U.S. Department of Health and Human Services

Drugs

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Questions and Answers: FDA Requires a Risk Evaluation and Mitigation Strategy (REMS) for Long-Acting and Extended-Release Opioids

On April 19, 2011 the Office of National Drug Control Policy (ONDCP) released the Obama Administration’s Epidemic: Responding to America’s Prescription Drug Abuse Crisis- a comprehensive action plan to address the national prescription drug abuse epidemic. 

This plan includes action in four major areas to reduce prescription drug abuse: education, monitoring, proper disposal, and enforcement. 

In support of the action plan, the FDA announced the elements of a Risk Evaluation and Mitigation Strategy (REMS) that will require all  manufacturers of long-acting and extended-release opioids to ensure that training is provided  to prescribers of these medications and to develop information that prescribers can use when counseling patients about the risks and benefits of opioid use.  The Food and Drug Administration Amendments Act of 2007 gave FDA the authority to require manufacturers to develop and implement a REMS when necessary to ensure the benefits of a drug or biological product outweigh its risks.

Q1.  What are long-acting and extended-release prescription opioids?

Long-acting and extended-release prescription opioids are analgesic medicines used primarily for the management of chronic moderate pain to severe pain. 

Prescription opioids are generally made as either immediate-release or extended-release products.  Immediate-release opioids work for shorter periods of time.  Extended-release opioids are designed to provide a longer period of drug release so that they can be taken less frequently.  Examples of opioids formulated as immediate-release and extended-release products include hydromorphone, morphine, oxycodone, oxymorphone, and tapentadol.  Long-acting opioids, such as methadone, also have a longer period of action because of the inherent characteristics of the drug substance which stays longer in the body, and not because of special design features of the finished product.

Q2.  What is a REMS?

A REMS is  a risk management plan that FDA can require a drug company to develop and implement to manage serious risks associated with a drug.  Under the Food and Drug Administration Amendments Act of 2007, FDA has the authority to require a manufacturer to develop a REMS when FDA finds a REMS is necessary to ensure that the benefits of a drug outweigh its risks. 

A REMS goes beyond a drug’s written prescribing information and can include a Medication Guide, communication plan, and other elements to assure safe use of a drug.  Every REMS is developed to address the unique risk-benefit profile of a drug or drug class.

Q3.  Why is FDA requiring a REMS for long-acting and extended-release prescription opioids?

Long-acting and extended-release prescription opioids can provide effective pain management for appropriately selected patients when used as directed.  However, there are serious risks associated with patients being prescribed these drugs who shouldn’t take them, or accidental or intentional improper use.  The amount of opioid contained in an extended-release tablet can be much more than the amount of opioid contained in an immediate-release tablet because extended-release tablets are designed to release the opioid over a longer period of time.  Long-acting opioids can take many hours to be cleared out of the body.  Improper use of any opioid can result in serious side effects including overdose and death and this risk is magnified with long-acting and extended-release opioids. 

It is important that health care professionals understand these risks when selecting and prescribing these drugs and adequately educate their patients so that they, too, understand these risks and how to use these products safely.  Although no opioid pain medications should be shared or stored so that others have access to them, for the reasons previously noted, a long-acting or extended-release opioid product may result in even greater risk than an immnediate-release opioid product if used by a person for whom it was not prescribed or if used improperly.  Patients need to be instructed about their responsibility for safe storage of these products to reduce the possibility of the drugs getting into the wrong hands.    

A REMS focused on prescriber education is intended to reduce the potential for serious adverse outcomes resulting from inappropriate prescribing, misuse and abuse of long-acting and extended-release opioids, while ensuring that patients with legitimate need for these drugs continue to have appropriate access to them. 

Q4.  What will the opioid REMS include?

The central component of the opioid REMS program is an education program for prescribers (e.g.,  physicians, nurse practitioners, physician assistants) and patients.

Prescribers

Prescriber education will include information on weighing the risks and benefits of opioid therapy, choosing patients appropriately, managing and monitoring patients, and counseling patients on the safe use of these drugs.  Additionally, prescribers will learn how to recognize evidence of and potential for opioid misuse, abuse and addiction. 

Patients

The opioid REMS will also include educational materials that prescribers can provide to patients on how to use and store these products safely.  Prescribers will be able to properly counsel patients on safe use and the responsibilities associated with using these products, and patients will receive Medication Guides when they pick up their prescriptions.  Medication Guides provide information in patient friendly language about the drug’s risks and how to use the drug safely. 

Q5. Which opioids will be required to have a REMS?

All long-acting and extended-release opioids will be required to have a REMS.  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:  List of Opioid Products Required to have a REMS.

Q6.  How will the REMS work?

This REMS requires manufacturers to develop an educational program for prescribers and patients and provide the educational materials either directly or through accredited continuing medical education (CME) providers.  In the REMS, manufacturers must describe their goals for the percentage of prescribers who complete the program at specified times.  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 to reduce the burden of the REMS on the healthcare system.

The opioid REMS education program will not include a mandatory requirement linked to the ability of healthcare professionals to prescribe long-acting and extended-release opioids at this time.  At this time, FDA is concerned that such a system would be overly burdensome on the healthcare system and could negatively impact access to these necessary medications.  In addition, it would require the establishment of a new system for registering prescribers of long-acting and extended- release opioids that would duplicate the existing DEA registration system.  The comprehensive action plan to address the national prescription drug abuse epidemic announces the Obama Administration’s intention to seek legislation to require prescriber education as a condition of obtaining DEA registration.    If this legislation is enacted, it will require mandatory education without requiring the manufacturers to create a duplicative registration system.  FDA intends to work with other Federal agencies to seek such legislation. 

Q7.  What does this announcement mean for healthcare professionals and patients who currently prescribe or take long-acting and extended-release opioids?

This announcement will alert healthcare professionals and patients about the importance of understanding the key messages associated with safe use of long-acting and extended-release opioids and the requirement for manufacturers of these products to make educational materials available for prescribers and patients.  It will take several months to develop these educational materials.  In the meantime, healthcare professionals may continue to prescribe long-acting and extended-release opioids as usual.  However, all prescribers are encouraged to thoroughly discuss the risks and benefits of these products with their patients.

Patients who are currently taking long-acting or extended-release opioids should continue to take their medications as directed.  Patients who have concerns about the medications they are taking should consult with their healthcare professional.

Q8.  Will this action make it harder for patients to get their pain treated?

The FDA understands how important it is for patients to get their pain treated. The REMS action is aimed at improving the education of physicians, to make them more familar with how best to use these drugs. When this happens, we believe physicians will be more knowledgeable about prescribing these drugs, which will hopefully improve access to these important medicines for patients with pain.  As part of the REMS, the FDA will monitor patient access to pain medicines and will continue to talk with the community of pain patients and physicians to ensure that patients get proper pain management.

Q9.  Has FDA consulted with stakeholder groups about the opioid REMS?

In 2009, FDA held several public meetings with various stakeholders to hear perspectives regarding the need for access to adequate options for pain management and about concerns associated with abuse of prescription opioids.  FDA also obtained their feedback regarding the development of a REMS for opioids.  Stakeholders who participated at the meetings included members of patient advocacy organizations, organizations representing prescribers, pharmacy organizations, insurance providers, and other government agencies.  In addition, FDA solicited written comments through a docket and received over 2,000 comments.  See: summary of comments.

FDA also held meetings with manufacturers of certain opioid products to discuss the process for designing and implementing a REMS without placing an unreasonable burden on the healthcare system.  For complete background information about these meetings, see: Meeting Information.

Q10.  Has the opioid REMS been discussed by an FDA Advisory Committee?

On July 22 and 23, 2010, a Joint Meeting of the FDA Anesthetic and Life Support Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee was convened to discuss FDA’s proposal for a class REMS for long-acting and extended-release opioids (for complete background information discussed at this meeting see: July 22-23, 2010 AC meeting.

The Advisory Committee members agreed that education of prescribers should be a central component of the REMS program. The Committee members suggested this education requirement be mandatory and linked to the existing system of prescriber registration with the Drug Enforcement Administration (DEA). 

A majority of the Advisory Committee members also recommended FDA require a REMS for all opioids, not just long-acting  (LA)  and extended-release  (ER) opioids. 

The FDA has decided not to require the REMS for all opioids.  The agency concluded that there is a disproportionate safety problem associated with the  ER and LA opioids which must be addressed, and will incorporate a step-wise approach to focus first on educating prescribers of ER and LA opioids. 

The FDA , for reasons further described in the response to questions 3 and 6, has also decided to make the education system voluntary at this time, and will work with the Administration to pursue legislation for a mandatory educational requirement linked to DEA registration requirements

Q11. Once the opioid REMS program is in effect, how will FDA monitor its effectiveness?

Manufacturers of long-acting and extended-release opioids will be required to monitor their REMS program to determine, among other things, how many prescribers are completing the educational programs and whether the REMS is adversely affecting patient access to necessary pain medications.  If FDA determines that this REMS is not meeting expectations, the Agency will reevaluate the program.

FDA also plans to work with outside organizations under the Safe Use Initiative to pursue other activities that can improve the safe use of long-acting and extended-release opioids.