Combined prolonged-release oxycodone and naloxone improves bowel function in patients receiving opioids for moderate-to-severe non-malignant chronic pain: a randomised controlled trial.
BACKGROUND
This randomised, double-blind, double-dummy, parallel-group multicentre study assessed the impact of a total daily dose of 60-80 mg oral oxycodone prolonged-release (PR)/naloxone PR (OXN PR) as fixed-ratio combination for patients with opioid-induced constipation (OIC) having moderate-to-severe, non-malignant pain.


METHODS
During pre-randomisation patients receiving opioids for moderate-to-severe non-malignant pain were converted to oxycodone PR (OXY PR) and titrated to an effective analgesic dose. During randomisation 265 patients on a stable OXY PR dose (60-80 mg/day) and with OIC were included in the full analysis population to receive OXN PR or OXY PR alone. Primary outcome was improvement in symptoms of constipation as measured by the Bowel Function Index (BFI). Secondary/exploratory outcomes examined analgesic efficacy and other bowel function parameters.


RESULTS
After 4 weeks of treatment, patients receiving OXN PR showed a significant improvement in bowel function compared with those in the OXY PR group (-14.9; 95% CI: -17.9, -11.9; p<0.0001) as measured by BFI which was seen after only 1 week of treatment continuing to the end of the study. After 4 weeks of treatment, patients receiving OXN PR had a median number of 3.0 complete spontaneous bowel movements (CSBM) per week compared with only 1.0 for OXY PR alone. Laxative intake was lower in the OXN PR than the OXY PR group. Furthermore, improvements in bowel function were achieved without loss of analgesic efficacy; pain intensity scores were comparable between the groups and consistent for duration of the study. Most frequently reported adverse events were consistent with those reported for opioid analgesics; no new or unexpected adverse reactions attributable to OXN PR used in higher doses were observed.


CONCLUSIONS
This study shows that the fixed-ratio combination of OXN PR is superior to OXY PR alone in terms of bowel function, while providing effective equivalent analgesia.
Löwenstein
O
O
Mundipharma Research GmbH & Co KG, Limburg (Lahn), Germany.
Leyendecker
P
P
Hopp
M
M
Schutter
U
U
Rogers
P D
PD
Uhl
R
R
Bond
S
S
Kremers
W
W
Nichols
T
T
Krain
B
B
Reimer
K
K
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D003248:Constipation / Q000139:chemically induced / Q000188:drug therapy*; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000008:administration & dosage / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D010098:Oxycodone / Q000008:administration & dosage / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome
D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D009292:Narcotic Antagonists; D009270:Naloxone; D010098:Oxycodone