FDA Approves Labeling with Abuse-Deterrent Features for Pfizer’s EmbedaBy
The US Food and Drug Administration (FDA) has approved new labeling for Pfizer’s 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 alternative treatment options are inadequate. Embeda is the third ER opioid analgesic to be approved with labeling describing the product's abuse-deterrent properties consistent with the FDA's 2013 draft guidance, Abuse-Deterrent Opioids â€“ Evaluation and Labeling. The new labeling includes a claim indicating that Embeda has properties that are expected to reduce oral abuse when the product is crushed.
â€‹Pfizer expected Embeda to be available in the US in early 2015. Embeda capsules consists of extended-release morphine sulfate and sequestered naltrexone hydrochloride, an opioid antagonist. Naltrexone is intended to remain sequestered when the product is taken as directed. The in vitro and pharmacokinetic data demonstrate that crushing Embeda pellets results in the simultaneous release and rapid absorption of morphine sulfate and naltrexone hydrochloride.
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 by releasing only the morphine in the capsule when taken properly. When crushed, the naltrexone in Embeda blocks some of the euphoric effects of the morphine and can precipitate withdrawal in persons dependent on opioids.
When swallowed intact, however, Embeda can still be abused or misused because the naltrexone is not expected to substantially block the euphoric effects of the morphine. It is unknown whether the abuse-deterrent properties of Embeda will result in a reduction in abuse by the intravenous route until additional postmarketing data are available. Embeda can still be abused or misused by any of these routes, and such abuse or misuse can cause an overdose that may result in death. If abused, it can also cause withdrawal in people who are dependent on, or tolerant to, opioids, according to the FDA.
Embeda was first approved on August 13, 2009, but was voluntarily withdrawn from the market in March 2011, due to testing that found stability concerns in the manufacturing process. The FDA confirmed that these issues were resolved with its approval of a manufacturing supplement in November 2013.
The FDA is requiring postmarketing studies of Embeda to further assess the effects of the abuse-deterrent features on the risk for abuse of Embeda and the consequences of that abuse. In addition, Embeda is part of the ER/LA Opioid Analgesics Risk Evaluation and Mitigation Strategy (REMS), which requires companies to make available to health care professionals educational programs on how to safely prescribe ER/LA opioid analgesics and to provide Medication Guides and patient counseling documents containing information on the safe use, storage, and disposal of ER/LA opioids.