UPDATE: FDA Has Approved New Labeling on Pfizer's Embeda

FDA approves labeling with abuse-deterrent features for third extended-releaseopioidThe U.S. Food and Drug Administration today approved new labeling for Embeda(morphine sulfate and naltrexone hydrochloride) extended-release (ER) capsules,an opioid analgesic to treat pain severe enough to require daily,around-the-clock, long-term opioid treatment and for which alternativetreatment options are inadequate. Embeda is the third ER opioid analgesic to beapproved with labeling describing the product's abuse-deterrent propertiesconsistent with the FDA's 2013 draft guidance, Abuse-Deterrent Opioids –Evaluation and Labeling . The new labeling includes a claim indicating that Embedahas properties that are expected to reduce oral abuse when the product iscrushed.Embeda has properties that are expected to reduce, but not totally prevent,abuse of the drug when crushed and taken orally or snorted. Embeda works byreleasing only the morphine in the capsule when taken properly. When crushed,the naltrexone in Embeda blocks some of the euphoric effects of the morphineand can precipitate withdrawal in persons dependent on opioids.When swallowed intact, however, Embeda can still be abused or misused becausethe naltrexone is not expected to substantially block the euphoric effects ofthe morphine. It is unknown whether the abuse-deterrent properties of Embedawill result in a reduction in abuse by the intravenous route until additionalpostmarketing data are available.Embeda can still be abused or misused by any of these routes, and such abuse ormisuse can cause an overdose that may result in death. If abused, it can alsocause withdrawal in people who are dependent on, or tolerant to, opioids."Preventing prescription opioid abuse and ensuring that patients have access toappropriate treatments for pain are both top public health priorities for theFDA,” said Sharon Hertz, M.D., acting director of the Division of Anesthesia,Analgesia, and Addiction Products in the FDA's Center for Drug Evaluation andResearch. “The science behind developing prescription opioids withabuse-deterrent properties is still evolving and these properties will notcompletely fix the problem. But they can be part of a comprehensive approach tocombat the very serious problem of prescription drug abuse in the U.S.”Embeda is not approved, and should not be used, for as-needed pain relief.Given Embeda's risks for abuse, misuse, and addiction, it should only beprescribed to people for whom alternative treatment options are ineffective,not tolerated or would be otherwise inadequate to provide sufficient painmanagement.Embeda was first approved on August 13, 2009, but was voluntarily withdrawnfrom the market in March 2011, due to testing that found stability concerns inthe manufacturing process. The FDA confirmed that these issues were resolvedwith its approval of a manufacturing supplement in November 2013.When Embeda was first approved, the drug was evaluated in a clinical trial of547 osteoarthritis patients. Additional data from abuse liability studiesconducted in laboratories and in people demonstrated the abuse-deterrentfeatures of Embeda for certain types of abuse (oral and snorting), when theproduct was crushed. The abuse potential for the intravenous route was studiedby simulating the amount of morphine and naltrexone that would be released uponcrushing Embeda. This study demonstrated that Embeda was less attractive toabusers or less likely to produce a high (lower “Drug Liking” and “Drug High”)compared with morphine alone. However, it is unknown whether these results withsimulated crushed Embeda predict a reduction in abuse by the intravenous routeuntil additional postmarketing data are available.The FDA is requiring postmarketing studies of Embeda to further assess theeffects of the abuse-deterrent features on the risk for abuse of Embeda and theconsequences of that abuse. In addition, Embeda is part of the ER/LA OpioidAnalgesics Risk Evaluation and Mitigation Strategy (REMS), which requirescompanies to make available to health care professionals educational programson how to safely prescribe ER/LA opioid analgesics and to provide MedicationGuides and patient counseling documents containing information on the safe use,storage, and disposal of ER/LA opioids.