Managing Chronic Moderate to Severe Pain—EMBEDA® (Morphine Sulfate and Naltrexone Hydrochloride) Extended Release Capsules for Oral Use

摘要: EMBEDA® (morphine sulfate and naltrexone hydrochloride) Extended Release Capsules for oral use, indicated for the management of chronic moderate to severe pain, contain extended-release pellets of morphine sulfate with a sequestered core of naltrexone, an opioid antagonist. When EMBEDA is taken orally as directed, it is bioequivalent with regard to rate and extent of plasma morphine absorption to KADIAN® (morphine sulfate extended-release) Capsules, a similar formulation without naltrexone. EMBEDA has been shown to be significantly superior to placebo in maintaining pain relief over 12 weeks and, in one of the longest durability studies, to reduce pain intensity for up to 12 months. Upon tampering by crushing EMBEDA, naltrexone is released to mitigate morphine-induced euphoria. Euphoria and drug-liking measures after oral administration of intact or crushed EMBEDA were similar, and were reduced compared with morphine sulfate solution; crushing EMBEDA did not yield more euphoria and desirability for abuse than the intact product. The most common adverse events after long-term use were constipation, nausea, and vomiting, which are typical of opioids. Over long-term use as directed, there was no evidence of naltrexone accumulation or opioid withdrawal. The impact of formulations such as EMBEDA on the abuse rate among real-world abusers requires long-term epidemiologic studies.