EMBEDA, New Opioid Approved with “Interim REMS”

The U.S. Food and Drug Administration (FDA) and King Pharmaceuticals, Inc. announced yesterday, August 13, 2009, that EMBEDA™ (extended-release morphine sulfate and naltrexone hydrochloride) has been approved. The product is for oral use in the management of moderate to severe pain requiring around-the-clock opioid analgesia. EMBEDA is the first FDA-approved long-acting opioid that is designed to reduce drug liking and euphoria when tampered with by crushing or chewing. King anticipates a September 2009 launch for EMBEDA.

Using King’s proprietary technology, EMBEDA capsules contain extended-release morphine pellets, each with an inner core of naltrexone, an opioid-receptor antagonist. If taken as directed, the morphine relieves pain while sequestered naltrexone passes through the body with no intended clinical effect. If pellets are crushed or chewed, the naltrexone is released and absorbed with the morphine, blocking morphine's subjective and analgesic effects. However, according to the manufacturer, the clinical significance of this effect has not been established, and there is no evidence that the naltrexone component reduces EMBEDA’s abuse liability.

However, it is still hoped that this new type of product will experience less misuse and abuse than other long-acting prescription opioids, which have become of great concern to the FDA. This latest product approval was a positive sign that the FDA is not holding up release of new opioid analgesics while pursuing development of their Risk Evaluation and Mitigation Strategy (REMS) initiatives for opioids. During an FDA teleconference, Bob Rappaport, MD, Director, FDA Division of Analgesics, Anesthetics, and Rheumatology Products, noted that EMBEDA will have an “interim REMS” consisting of a medication guide and special communications sent to prescribers explaining this new drug. [Click for prescribing information and medication guide.]

Rappaport further commented that the opioid REMS initiative is probably the largest project that the FDA has ever pursued, but he did not give a date for finalization. He reiterated that the FDA wants to preserve accessibility of opioids for patients with pain but is determined to put an end to the “epidemic of abuse and addiction” surrounding opioid analgesics. He further said that either the FDA will accomplish this goal or “somebody else will step in and do it.” The implication seemed to be that the “somebody else” (he didn’t say who) would be more uncompromising and restrictive than the FDA.