September 28, 2017
By: Scott Gottlieb, M.D.
FDA Commissioner Scott Gottlieb, MD
America is awash in immediate-release (IR) opioids. About 90 percent of all opioid pain medications prescribed – or 160 million prescriptions a year – are for IR formulations like hydrocodone and acetaminophen or oxycodone and acetaminophen combinations. Many people who are currently addicted to opioids became medically addicted. Their first exposure to opioids was from a legal prescription, and for many, that prescription was written for an IR formulation of these drugs. Many addicted patients may then move on to higher dose formulations or more accessible illegal street drugs.
At FDA, we believe it’s necessary to continue to take steps to address both ends of this continuum, the potential gateway to addiction that is often the IR formulations, and the higher dose, extended-release formulations, both of which carry a significant risk of overdose and mortality. We are taking several actions to address these challenges. This week, we issued letters notifying 74 manufacturers of IR opioid analgesics intended for use in the outpatient setting that their drugs will now be subject to a more stringent set of requirements under a Risk Evaluation and Mitigation Strategy (REMS). The REMS requires that training be made available to health care providers who prescribe IR opioids, including training on safe prescribing practices and consideration of non-opioid alternatives.
FDA also will soon issue a final guidance document that will assist potential applicants who plan to develop, and submit to FDA, an application to seek approval of a generic version of abuse-deterrent formulations (ADFs) of opioid drugs. Most of the currently approved opioids with labeling describing abuse-deterrent properties are extended release/long-acting (ER/LA) formulations of opioids. These drugs are generally formulated to be more resistant to the sort of manipulation that would otherwise make them amenable to snorting and/or injecting. Addicted patients who start by using the IR drugs will sometimes migrate onto the ER/LA formulations, and then try to manipulate those higher-dose formulations in ways that can provide a more immediate “high” through injection or snorting. But there are currently only brand name ADF formulations. These steps that FDA is taking are aimed at addressing each end of the spectrum of abuse and addiction.
With respect to the new REMS measures to address the safer use of the IR opioid pain medications, these short-acting drugs will now be subject to the same regulatory requirements as the ER/LA opioid analgesic formulations. Since 2012, manufacturers of ER/LA opioid analgesics have been subject to a REMS, which requires, as its primary component, that training be made available to prescribers of those products. To meet this requirement, the sponsors of the ER/LA opioid analgesics have been providing unrestricted grants to accredited continuing education providers for the development of education courses for health care professionals based on content outlined by FDA, which the agency calls the “Blueprint.” FDA is now extending these REMS requirements to the IR manufacturers.
While some of the ER/LA manufacturers also make IR opioids, today’s action will greatly expand the number of products covered by the REMS. The existing REMS currently includes 64 ER/LA opioid analgesic products. Once the action is finalized, an additional 277 IR opioid analgesics will be subject to these REMS requirements.
In addition to expanding the REMS to include IR products, FDA is modifying the content of the educational “Blueprint” required under the REMS. The agency is adding content on pain management, including non-opioid alternatives. This includes principles related to the acute and chronic pain management; non-pharmacologic treatments for pain; and pharmacologic treatments for pain (both non-opioid analgesic and opioid analgesic). The revised Blueprint will also cover information about the safe use of opioids, and basic information about addiction medicine and opioid use disorders.
For the first time, this training will also be made available to other health care professionals who are involved in the management of patients with pain, including nurses and pharmacists, which is in addition to prescribers of opioid analgesics. FDA believes that all health care professionals involved in the management of patients with pain should be educated about the safe use of opioids so that when they write or dispense a prescription for an opioid analgesic, or monitor patients receiving an opioid analgesic, they can help ensure that the product is properly indicated for the patient and used under appropriate clinical care.
FDA’s new Opioid Policy Steering Committee is also considering whether there are circumstances when FDA should require some form of mandatory education for health care professionals, and how the agency would pursue such a goal. The agency’s purpose is to reduce overall exposure to opioids by making certain that prescribing doctors are properly informed about appropriate prescribing recommendations, that providers understand how to identify the risk of abuse in individual patients, and know how to get addicted patients into treatment. In fact, today, the agency issued a public notice to solicit input on a detailed series of questions related to these goals. FDA has also been scheduling meetings with provider organizations and sponsors engaged in dispensing drugs – including health systems and pharmacy chains, in an effort to solicit additional input on new strategies.
Sending out the manufacturer notification letters is the first step in extending the REMS to the IR drugs. This process could take about a year to finalize. The modified REMS will continue to include a requirement for patient Medication Guides, patient-counseling documents, and plans for assessing the effectiveness of the revised REMS. The crisis of opioid addiction is a public health tragedy of enormous proportions. By putting in place safety measures for IR opioid analgesics, and creating a more robust path to converting the high dose opioids to formulations that are more resistant to manipulation, we are addressing both ends of this crisis. Our hope is that we can help prevent new patients from becoming addicted, and keep some individuals from experiencing the serious adverse effects associated with these medications.
Scott Gottlieb, M.D., is Commissioner of the U.S. Food and Drug Administration