Oxycodone/Naloxone Prolonged-Release: A Review of Its Use in the Management of Chronic Pain While Counteracting Opioid-Induced Constipation

A combination of prolonged-release (PR) oxycodone with PR naloxone (Targin®, Targiniq®, Targinact®) in one tablet with a fixed 2:1 ratio is available for the treatment of patients with severe pain, which can only be adequately managed with opioid analgesics. The aim of this formulation is to counteract opioid-induced constipation through the local antagonist effect of naloxone in the gut wall, while maintaining analgesia due to the low bioavailability of oral naloxone. Three large, 12-week, randomized, double-blind, phase III trials in patients with moderate to severe, chronic, non-malignant pain, plus a prospectively planned pooled analysis of two of these studies, demonstrated that oxycodone/naloxone PR improved bowel function, as measured by the bowel function index, compared with oxycodone PR. Additionally, oxycodone/naloxone PR relieved pain more effectively than placebo and no less effectively than oxycodone PR after 12 weeks. Phase II efficacy data in cancer patients are consistent with those observed in patients with non-malignant pain. Oxycodone/naloxone PR was generally well tolerated; the most frequently reported adverse events were of gastrointestinal origin, consistent with those known to occur with opioid therapy. Of note, numerically lower rates of constipation were observed in the oxycodone/naloxone PR group compared with the oxycodone PR group. A cost-utility analysis predicted that oxycodone/naloxone PR would be a cost-effective option compared with oxycodone PR in patients with non-malignant pain. Although more comparative data are needed, oxycodone/naloxone PR is an effective option for use in patients with severe chronic pain, particularly among those with opioid-induced constipation.