Opioid analgesics are important pain medications that are widely prescribed for both non-cancer and cancer-related pain. Opioid drugs provide significant benefits for patients when used properly for their approved indications. However, opioids also carry a risk of abuse, misuse and death. More than 15,500 people died in the United States in 2009 after overdosing on narcotic pain relievers. That’s a 300 percent increase over the last 20 years. And for each death, there are an additional ten treatment admissions, 32 emergency department visits and 825 nonmedical users of these drugs. FDA is extremely concerned about the inappropriate use of opioids, which has become a major public health challenge for our nation.
An impassioned, sometimes heated, debate has occurred in the medical and health policy communities about the best ways to ensure that opioids are used appropriately while working to prevent any further tragedies. As FDA reviews opioid medical products, requires accurate drug prescribing information, and monitors how these products are used once they go to market, the agency must strike a balance between their benefit in treating patients with moderate to severe pain and the risks associated with misuse, abuse and addiction to those patients and to others.
Combating opioid misuse, abuse, and addiction has long been a priority for the Agency, and FDA has taken many steps to address this problem over the last few decades.
However, FDA recognizes that we can do more and has established a task force to build upon existing initiatives and develop new ones. The task force has embarked on a multi-pronged and targeted approach aimed at combating misuse, abuse and addiction at critical points in the lifecycle of an opioid product, from development through use. The task force's multi-pronged approach currently targets:
- Drug Development
- Opioid Labeling
- Prescriber Education
- Patient Education
- Exploring Innovative Packaging/Storage to Prevent Abuse
- Encouraging the Development of Products that Treat Abuse and Overdose
- Role of Other Agencies
Improving the Science Regarding Opioids - The task force’s comprehensive approach begins with basic science. For example, physicians and regulators need more information about whether, and how, opioids should be used for treating chronic pain. Given the nature of chronic pain, some of these drugs are now being prescribed for long periods of time. Understanding patient pain needs, prescribers use, possible dependence or addiction and other critical areas will help inform and guide proper labeling and prescribing of these necessary but powerful medications.
- In Oct. 2012, FDA was a co-host of a scientific workshop to find ways to improve analgesic drug discovery and development.
- On Feb. 7-8, 2013, FDA will hold a public meeting on the Impact of Approved Drug Labeling on Chronic Opioid Therapy. One of the topics to be addressed is the science of pain, the difference between cancer and non-cancer pain and how pain is measured.
- FDA is involved in several ongoing public-private partnerships aimed at improving the science that underlies the use of opioids. These include:
- Work with Brandeis University on how to combine and analyze data from Prescription Drug Monitoring Programs from several states to better identify problematic prescribing patterns. These statewide electronic databases collect data on controlled substances dispensed in the state.
- Work with a group of academics and other scientists to develop a trial to assess the effectiveness of opioids in the treatment of chronic non-cancer pain.
- Work with a variety of outside stakeholders to develop a model Patient-Prescriber Agreement that could be used to support the safer prescription of opioids.
Developing Abuse-Deterrent Formulations – One important FDA effort in reducing abuse and misuse is encouraging the development of opioids that are specifically formulated to deter abuse. Abuse-deterrent formulations target the known or expected routes of abuse, such as crushing in order to snort or dissolving in order to inject, for the specific opioid drug substance in that formulation. The science of abuse deterrence is relatively new, and both the formulation technologies and the analytical, clinical, and statistical methods for evaluating those technologies are rapidly evolving. FDA considers the development of abuse-deterrent formulations to be a public health priority and is encouraging their development.
- On Jan. 9, 2013 FDA issued a draft guidance document (PDF - 463KB) to assist industry in developing new formulations of opioid drugs with abuse-deterrent properties. FDA intends to take a flexible, adaptive approach to the evaluation and labeling of potentially abuse-deterrent products.
- FDA is planning to hold a public meeting later this year to further discuss this issue.
- FDA has concluded that if FDA determines that a formulation of a product significantly deters abuse, the Agency has the legal authority under the Food Drug and Cosmetic Act to require generic versions of that product to have abuse-deterrent formulations as well.
The primary tool used by FDA to inform prescribers and patients about the best uses of medications is the approved product label. FDA has made many changes to opioid medication labels in an effort to improve their use. As a part of this work, FDA routinely discusses labeling with Advisory Committees composed of outside experts. Examples of such discussions include:
- On Jan. 24-25, 2013, an FDA advisory committee met to discuss the public health benefits and risks, including the potential for abuse, of drugs containing hydrocodone. This meeting, which was originally scheduled for October 2012, had been postponed because of Hurricane Sandy.
- FDA has asked scientific experts and the public to discuss the issues related to the entire class of opioids at a Feb. 7-8, 2013 public meeting. The meeting is focused on the approved labeling and how it is used in clinical practice. For example, to help guide potential changes to labeling, the agency is asking what data support a maximum daily dosage and restrictions on duration of use depending on type of pain (cancer and non-cancer) and how restricting use of these drugs to patients with severe pain alone might affect prescribing practices, patient access to pain medication, patient pain control and the abuse and misuse of opioid medicines.
Outreach/Collaboration with Key Members of the Prescribing Community – Prescribers have an important role to play in preventing the use and abuse of opioids. FDA intends to reach out to key members of the health care professional community to find out what they are doing to combat this problem and whether FDA can do anything to help them with their efforts.
Educating Prescribers about Opioid Use - FDA believes it is critically important to facilitate prescribers’ education about the best uses of opioids, including knowing when and for which patients they should be used.
- Last July FDA mandated a Risk Evaluation and Mitigation Strategy (REMS) for extended-release and long-acting (ER-LA) opioids. The final REMS, required that manufacturers set up training programs and make available education materials on the safe use of these products for all U.S. licensed opioid prescribers starting March 1, 2013. While the programs will be funded by unrestricted grants from product manufacturers, they will be offered by independent providers of continuing education (CE) as part of the REMS. Content for the training will be based on an FDA blueprint that has been developed with input from a wide range of stakeholders, including:
- Information on weighing the risks and benefits of opioid therapy, choosing patients appropriately, managing and monitoring these patients, and counseling them on the safe use of these drugs. The training will also emphasize how to recognize potential and actual misuse, abuse, and addiction.
While prescribers are not required to take this training, FDA will encourage them to do so in order to have adequate and up-to-date training in the safe and effective use of opioid medications.
- Labeling is a critical tool in the education of prescribers and patients. As part of last year’s REMS for ER-LA opioids, manufacturers revised the approved labeling for these products to improve both their content and their ease of use. For example, the Medication Guides, which are intended to be given to patients with each prescription, were updated to include the latest important information on how to use these powerful medications safely and effectively.
In addition to implementing prescriber education through the ER-LA opiod REMS, FDA strongly supports the Administration's call to “Work with Congress to amend Federal law to require practitioners (e.g., physicians, dentists) who request DEA registration to prescribe controlled substances to be trained on responsible opioid prescribing practices as a precondition of registration. This training would include assessing and addressing signs of abuse and/or dependence.” [Epidemic: Responding to America’s Prescription Drug Abuse Crisis – 2011 Office of National Drug Control Policy (PDF - 306KB) ]
It is essential that prescribers help their patients by educating them about the appropriate use of these powerful drugs.
As a part of the ER-LA REMS manufacturers are also required to make available to prescribers educational materials for patients that provide targeted, patient-friendly information about the best uses of specific opioid medications.
FDA has created other materials to help educate patients on how to use opioids. For example, as mentioned above, Medication Guides for ER-LA opioids were re-written as a part of the REMS, and should be given to every patient who receives an ER-LA prescription. Prescribers should encourage patients to read these important materials, which also inform patients on safe disposal of their unused opioids.
FDA also partners with outside organizations to help educate patients about the best uses of opioids. It participates in a drug abuse campaign sponsored by DrugFree.org (formerly the Partnership for Drug Free America) and is a member of the National Council on Patient Information and Education, which is running a campaign targeting teens and college students on prescription drug abuse.
Finally, FDA maintains a website to educate patients on the appropriate disposal of medications once they’re no longer needed, which includes instructions on how to dispose of opioids safely. Medicines play an important role in treating many conditions and diseases, but when they are no longer needed it’s important to dispose of them properly to avoid harm to others. On the website, FDA lists some disposal options and some special disposal instructions for patients to consider when throwing out expired, unwanted, or unused medicines.
Beyond the printed label, FDA is also interested in exploring whether innovative package/storage designs for opioids can prevent or deter misuse and abuse by patients who receive legitimate opioid prescriptions, and misuse and abuse by others. Examples include a variety of systems designed to dispense medications as scheduled while preventing inappropriate access for abuse.
Naloxone is an injectable medicine that can rapidly reverse the overdose of either prescription (e.g., oxycodone) or illicit (e.g., heroin) opioids. While naloxone is the standard treatment for opioid drug overdoses, it is most commonly used by trained medical personnel in emergency departments and on ambulances. There is widespread interest by prescribers, patients and advocates in exploring the broader uses of naloxone, including its use in non-medical settings such as the home.
- FDA held a public meeting in April 2012 where these issues were discussed and the regulatory pathways for development laid out by senior FDA staff. FDA has been working to support the development of new formulations of naloxone, such as intranasal or autoinjector formulations that would be easier to use in non-medical settings.
As can be seen from the number of activities discussed above, FDA is involved in a variety of activities aimed at improving the use of opioid medications in the United States. Given the complexity of addressing opioid abuse, however, these problems require the concerted efforts of federal, state and local agencies as well as the engagement of health care professionals, patients and addiction/pain specialists.