The role of Embeda (morphine sulfate-naltrexone hydrochloride) in opioid abuse: a systematic review of literature

The struggle to balance the analgesic needs of the patient and reduce public health concerns of prescription opioid abuse have led to the development of abuse resistant opioid formulations. Embeda is a novel abuse resistant opioid formulation consisted of extended release morphine sulfate with sequestered naltrexone hydrochloride. The method of abuse deterrence involves a release of naltrexone to counteract the effects of morphine sulfate if the capsule is compromised by crushing. A systematic review of literature was conducted to evaluate whether Embeda reduces opioid abuse. A search from 2004-2011 was done using PubMed, OVID, Scopus, and National Library of Medicine Drug Information Portal using terms: Embeda, morphine/naltrexone, and opioid abuse. Twelve studies to date have been reviewed by the FDA in the evaluation of Embeda but only 3 studies evaluated the abuse potential. In a randomized double-blinded study 32 subjects were evaluated for subjective effects of Embeda whole, Embeda crushed, morphine sulfate solution, & placebo. Results produced statistically significant (p<0.01) degree of increased euphoria in morphine sulfate solution population than crushed Embeda at similar plasma concentrations. A second randomized double-blinded study evaluated the effect of dose ranging naltrexone on morphine induced euphoria in 27 subjects. Results from the second study showed that only naltrexone at 4.8mg dose produced statistically significant reduction in morphine induced euphoria. The third study was a randomized double-blinded study that evaluated euphoric effects of intravenous morphine alone versus combination with naltrexone in 28 subjects. The results of the study showed statistically significant 71% reduction in euphoria compared to IV morphine alone. All three studies were conducted in non-opioid dependent subjects. In conclusion all three studies showed statistically significant reduction in euphoric effects of crushed Embeda but there is no evidence to prove a reduction of abuse in opioid-dependent individuals.