Oral oxycodone/naloxone prolonged release (PR) [Targin, Targinact, Targiniq] is a 12-hourly opioid receptor agonist and opioid receptor antagonist fixed-dose combination product that is approved in countries in the EU for the management of severe pain (adequately manageable only with opioid analgesics) in adults. Oral naloxone prevents oxycodone from binding to μ-receptors in the gastrointestinal (GI) tract, thereby counteracting opioid-induced constipation (OIC). In short-term (5- to 12-week) clinical trials of adults with moderate to severe, chronic pain and OIC (OXN3001, OXN3006, OXN3506), oxycodone/naloxone PR significantly improved OIC while providing noninferior analgesia relative to oxycodone PR; results were consistent between cancer and non-cancer patients in OXN3506. Analgesia and improvements in bowel function were sustained with an additional 24-52 weeks of oxycodone/naloxone PR treatment in long-term extension studies. Results in real-world studies were consistent with those in clinical trials. Oxycodone/naloxone PR was generally well tolerated, with nausea, hyperhidrosis, and diarrhoea (generally transient) reported as the most commonly occurring adverse events. Thus, oxycodone/naloxone PR is a useful treatment option to consider in adults with severe chronic pain that can be adequately managed only with opioid analgesics, particularly in those with OIC.