Fixed combination of oxycodone with naloxone: a new way to prevent and treat opioid-induced constipation

Morphine and other opioids increase tone and reduce propulsive motility in several segments of the gut, enhance absorption of fluids, and inhibit secretion. This opioid-induced bowel dysfunction may present as infrequent stools, hard stools, difficult defecation, bloating, and sense of incomplete emptying of the bowels, but also dry mouth, gastroesophageal reflux, epigastric fullness, and abdominal cramping. It afflicts about one-third of patients on opioid treatment. Lifestyle measures, such as regular toilet visits, physical activity, and fiber-rich diet, are very unlikely to be successful. Laxatives, such as bisacodyl, sodium picosulfate, sennosides, macrogols, and prucalopride, may relieve opioid-induced constipation (OIC) in a proportion of patients only. A new approach to counteract OIC is the coadministration of an opioid antagonist devoid of the potential to penetrate the brain. In the EU, an oxycodonenaloxone combination has been approved for this purpose. Both components are included in an oral extended-release preparation. Following its release, naloxone acts locally on the gut and antagonizes the inhibitory effect of the opioid. After being absorbed in parallel with oxycodone, naloxone is rapidly and completely inactivated by a high first-pass effect in the liver. In a 2:1 dose ratio it may improve OIC without interfering with the analgesic effect.