EmbedaTM: morphine sulfate extended-release capsules with sequestered naltrexone, a novel opioid formulation for the treatment of chronic pain

Opioids have been known to have analgesic properties for thousands of years. The chronic use of opioids for the treatment of chronic noncancer pain has only lately seen increased medical practice [1] owing to a relative lack of efficacy data, until recently, from well-controlled studies. The efficacy of morphine, oxycodone and oxymorphone in extended-release dosage forms has been demonstrated in randomized, placebocontrolled, double-blind clinical trials for the treatment of pain related to osteoarthritis, low back pain and neuropathic pain [2–6]. The use of chronic opioid therapy in the treatment of chronic cancer pain has been well established as safe and effective in countless clinical trials around the world [7]; however, the use of chronic opioids for the management of chronic noncancer pain has been associated with misuse by patients, pseudopatients, recreational drug users and individuals with an opioid addiction disorder [8]. It has been estimated that the nonmedical use of prescription opioids has increased fourfold in the last 20 years with prescription opioid abuse more prevalent than most street drugs and similar to trends observed for marijuana [9]. Since chronic opioid therapy is beneficial for some pain patients there has been an interest in developing opioid dosage forms that provide opioid analgesia yet are difficult to divert to nonmedical uses. Chronic noncancer pain, such as low back pain and osteoarthritis pain, affect up to 20% of the population of western countries [1]. With the introduction of extended-release opioid products [10] the physician has some tools to combat pain and suffering among some patients with chronic pain. However, the primary physician also has to attempt to limit the diversion of prescribed opioid medications and, thus, protect the public. There are many methods advocated to help diminish the risk of prescription opioid abuse. First, all physicians are encouraged to complete a full pain history and physical examination, including a pain diagnosis and differential diagnosis. Next, patients should be initially treated with nonopioid analgesics and nondrug treatments, such as physical therapy, massage, electrical stimulation and cognitive therapies. Physicians are encouraged to treat patients with interventional injective therapies when appropriate. If chronic opioid therapy is required, the treating physician should complete screening tools to identify patients at risk for opioid abuse prior to initiation of therapy [11]. Patients may be asked to sign medication agreements to help ensure compliance, and random and intermittent urine drug screens will help identify compliance with prescribed treatment [12]. All patients should be considered to have a ‘trial’ of opioid medications and, when opioid therapy is unsuccessful or associated with unacceptable side effects, the opioids should be discontinued and other treatments instituted [13]. Recent guidelines have suggested that physicians should carefully re-evaluate patients who require high doses of opioids, defined as greater than 200 mg daily of morphine [14]. Chronic opioids are often used in the management of chronic osteoarthritis pain. EmbedaTM (Alpharma Pharmaceuticals, NJ, USA) is a novel and recently approved (in the USA) extended-release formulation of morphine. It combines morphine with a sequestered, inner core of naltrexone (an opioid antagonist) that is not significantly absorbed when the capsule is taken as directed (whole). Should the capsule be tampered with, such as crushing or chewing, the naltrexone will be released, absorbed and counter the opioid effect. It is hoped that this combination morphine product will help deter patients or addicts from inappropriate use of opioids. Short-term clinical trials of Embeda demonstrate analgesia and improved physical functioning among patients with chronic pain related to osteoarthritis. This article reviews the chemistry, clinical efficacy and possible role of Embeda for the management of chronic pain.