Long‐term efficacy and safety of oxycodone‐naloxone prolonged‐release formulation (up to 180/90 mg daily) – results of the open‐label extension phase of a phase III multicenter, multiple‐dose, randomized, controlled study

BACKGROUND: The inclusion of naloxone with oxycodone in a fixed combination prolonged‐release formulation (OXN PR) improves bowel function compared with oxycodone (Oxy) alone without compromising analgesic efficacy. In a recent 5‐week, randomized, double‐blind comparative trial of OXN PR and OxyPR, it could be shown that the beneficial properties of OXN PR extend to doses up to 160/80 mg. METHODS: Bowel function, pain, quality of life (QoL) and safety of OXN PR up to 180/90 mg daily were evaluated in a 24‐week open‐label extension phase of the 5‐week randomized comparative study in patients with non‐malignant or malignant pain requiring opioids and suffering from opioid‐induced constipation. RESULTS: During treatment with a mean (SD) daily dose OXN PR of 130.7 (26.56) mg (median, maximum: 120 and 180 mg), the Bowel Function Index (BFI) decreased from 45.3 (26.37) to 26.7 (21.37) with the largest decrease seen in the first week. The average pain over the last 24 h remained stable (median Pain Intensity Scale score 4.0) and QoL was maintained throughout the study. Adverse events were consistent with the known effects of OXN PR and no new safety concerns emerged. Equivalent efficacy and safety benefits were observed in cancer patients. CONCLUSIONS: The OXN PR in doses up to 180/90 mg provides effective analgesia with maintenance of bowel function during long‐term treatment. The beneficial effects of such dose levels of OXN PR contribute to stable patient‐reported QoL and health status despite serious underlying pain conditions, such as cancer. SIGNIFICANCE: In patients with pain requiring continuous opioid therapy at doses above 80 mg of oxycodone, stable and effective long‐term analgesia can be achieved using OXN PR up to 180/90 mg daily without compromising bowel function and may be preferential to supplemental oxycodone.