Review: Prolonged-Release Opioid Combo Treats Pain and Opioid-Induced Constipation Safely and Effectively


A recent study looked at the safety and efficacy of prolonged-release forms of two common opioids-oxycodone and naloxone-in treating chronic pain and opioid-induced constipation, which affects in as many as 40% of opioid-treated patients.

Chronic pain is debilitating all on its own, but the fact that it can result in depression, anxiety, and loss of independence, among other things, makes it a significant detriment to patients’ quality of life. Chronic pain is associated with many medical conditions; in patients with cancer, up to 70% experience chronic pain. Treatment can involve nonpharmacologic therapy, but it more often includes non-opioid analgesics, nonsteriodal anti-inflammatory drugs (NSAIDS), and, in cases of moderate-to-severe pain, opioids.

Opioids, of course, are often effective, but they also often bring adverse events, including headache, fatigue, and opioid-induced constipation (OIC) in as many as 40% of opioid-treated patients. OIC also doesn’t typically disappear as rapidly as other adverse effects, which often occur at the start of treatment but then wane. Laxatives that treat OIC don’t address its underlying mechanisms.

A recent review in Drug Design, Development, and Therapy looked at the safety and efficacy of prolonged-release forms of two common opioids—oxycodone and naloxone—in treating chronic pain and OIC. Oxycodone is an opioid receptor agonist commonly used for the treat­ment of patients with moderate-to-severe pain. Oxycodone stimulates opioid receptors in the gastrointestinal tract, modifying normal bowel activity and reducing gut motility, potentially resulting in constipation. Naloxone is an opioid receptor antagonist with low systemic bioavailability. When administered orally, naloxone antagonizes the opioid receptors in the gut wall, while its extensive first-pass hepatic metabolism ensures the lack of antagonist influence on the central-mediated analgesic effect of the opioids.Does a for­mulation consisting of oxycodone and naloxone (PR OXN) in a 2:1 ratio in a prolonged-release formula achieve the desired analgesic effects while minimizing or preventing OIC?

In short, yes.

First, the review looked at studies on OIC and attempts to treat it using laxatives. The study authors note, “…Since OIC has a unique etiology, they are not really effective in its treatment…Opioids delay gastric emptying and prolong transit time throughout the small and large intestines. For these reasons, laxatives, which predominantly act on the colon, frequently do not address the symptoms of OIC.” Laxatives are also associated with potential side effects including bloating, gas, and gastroesophageal reflux—which may lead to lack of tolerability and medication adherence.

Next, the review looked at PR OXN in prevention and treatment of OIC, citing several randomized controlled trials (RCTs) that have reported on the comparable analgesic efficacy of PR OXN and prolonged-release oxycodone (PR OXY), with a clinically relevant improvement in OIC in various types of pain. “When administered orally, naloxone antagonizes the opioid receptors in the gut wall, potentially reducing OIC, while its extensive first-pass hepatic metabolism ensures the lack of antagonist influenceon the central analgesic effect.”

Another study compared prolonged-release oxycodone monotherapy with PR OXN, in which patients were treated with PR OXY for at least the last 30 days before PR OXN treatment. While on PR OXY, the patients reported OIC despite the use of at least two different laxatives with different mechanisms of action. PR OXN was superior to PR OXY in terms of pain relief, OIC, and quality of life.

The review also looked at longer-duration studies of PR OXN, which is important for osteoarthritis patients and spine pain patients, who are typically on long-term opioid treatment schedules, and the safety and efficacy of PR OXN in older patients. In both instances, the review found that PR OXN is effective as pain medication, and that prevention and treatment of OIC improves adherence to opioid pain therapy, leading to improved quality of life.

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