Open Access Open Access  Restricted Access Subscription or Fee Access

Oxycodone/naloxone in postoperative pain management of surgical patients

Ioannis D. Gkegkes, MD, PhD, Evelyn Eleni Minis, MD, Christos Iavazzo, MD, MSc, PhD


Background: The role of analgesia is crucial in the management of postoperative pain. Different combinations of oral analgesics have been proposed in the past. The oxycodone/naloxone (OXN) combination is a recent addition and is being used by different surgical specialties. The aim of our study was to clarify the possible role, advantages, and disadvantages of OXN in the pain management of surgical patients.

Method: The authors retrieved the included studies after performing a systematic search in PubMed and Scopus.

Results: Ten studies (six randomized controlled trials, three retrospective studies, and a prospective study) were eligible for inclusion in this review. In total, 1,996 patients were included. Six studies reported on orthopedic procedures while four studies referred to colorectal, gynecologic, cardiac, and thoracic surgery procedures, respectively. The analgesic effect of OXN was evaluated in nine out of 10 studies, where OXN showed superiority only in two out of nine studies. Postoperative bowel function was evaluated in seven out of 10 studies. Patients treated with OXN did not show any significant differences in bowel function when compared to control groups. No superiority was found regarding the possible adverse events.

Conclusion: Analgesia is crucial to postoperative recovery. Pain control can be achieved a combination of different analgesics, including OXN. This oral analgesic combination can have the potential to minimize side effects, such as opioid-induced constipation and optimize the recovery period.


postoperative analgesia, analgesics, postoperative pain, opioid-induced constipation, opioids, oxycodone, naloxone

Full Text:



Iavazzo C, Gkegkes ID: Enhanced recovery programme in robotic hysterectomy. Br J Nurs. 2015; 24: S4-S8.

Kehlet H, Wilmore DW: Evidence-based surgical care and the evolution of fast-track surgery. Ann Surg. 2008; 248: 189-198.

Kurz A, Sessler DI: Opioid-induced bowel dysfunction: Pathophysiology and potential new therapies. Drugs. 2003; 63: 649-671.

DePriest AZ, Miller K: Oxycodone/naloxone: Role in chronic pain management, opioid-induced constipation, and abuse deterrence. Pain Ther. 2014; 3: 1-15.

Iyer S, Davis KL, Candrilli S: Opioid use patterns and health care resource utilization in patients prescribed opioid therapy with and without constipation. Manag Care. 2010; 19: 44-51.

Kwong WJ, Diels J, Kavanagh S: Costs of gastrointestinal events after outpatient opioid treatment for non-cancer pain. Ann Pharmacother. 2010; 44: 630-640.

Liberati A, Altman DG, Tetzlaff J, et al.: The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration. PLoS Med. 2009; 6: e1000100.

Kuusniemi K, Zollner J, Sjovall S, et al.: Prolonged-release oxycodone/naloxone in postoperative pain management: From a randomized clinical trial to usual clinical practice. J Int Med Res. 2012; 40: 1775-1793.

Ruetzler K, Blome CJ, Nabecker S, et al.: A randomised trial of oral versus intravenous opioids for treatment of pain after cardiac surgery. J Anesth. 2014; 28: 580-586.

Comelon M, Wisloeff-Aase K, Raeder J, et al.: A comparison of oxycodone prolonged-release vs. oxycodone + naloxone prolonged-release after laparoscopic hysterectomy. Acta Anaesthesiol Scand. 2013; 57: 509-517.

Scardino M, Grappiolo G, Gurgone A, et al.: Single-shot epidural-spinal anesthesia followed by oral oxycodone/naloxone and ketoprofen combination in patients undergoing total hip replacement: Analgesic efficacy and tolerability. Minerva Anestesiol. 2015; 81: 19-27.

Kampe S, Weinreich G, Darr C, et al.: Controlled-release oxycodone as "gold standard" for postoperative pain therapy in patients undergoing video-assisted thoracic surgery or thoracoscopy: A retrospective evaluation of 788 Cases. Thorac Cardiovasc Surg. 2015; 63: 510-513.

Di Giorgio L, Sodano L, Touloupakis G, et al.: [The management of post-surgical pain in the patient treated for hallux valgus with percutaneous and minimally invasive technique]. Clin Ter. 2014; 165: e115-118.

Oppermann J, Bredow J, Spies CK, et al.: Effect of prolonged-released oxycodone/naloxone in postoperative pain management after total knee replacement: A nonrandomized prospective trial. J Clin Anesth. 2016; 33: 491-497.

Kokki M, Kuronen M, Naaranlahti T, et al.: Opioid-induced bowel dysfunction in patients undergoing spine surgery: Comparison of oxycodone and oxycodone-naloxone treatment. Adv Ther. 2017; 34: 236-251.

Haeseler G, Schaefers D, Prison N, et al.: Combatting pain after orthopedic/trauma surgery- perioperative oral extended-release tapentadol vs. extended-release oxycodone/naloxone. BMC Anesthesiol. 2017; 17: 91.

Creamer F, Balfour A, Nimmo S, et al.: Randomized open-label phase II study comparing oxycodone-naloxone with oxycodone in early return of gastrointestinal function after laparoscopic colorectal surgery. Br J Surg. 2017; 104: 42-51.

Parvizi J, Miller AG, Gandhi K: Multimodal pain management after total joint arthroplasty. J Bone Joint Surg Am. 2011; 93: 1075-1084.

Duellman TJ, Gaffigan C, Milbrandt JC, et al.: Multi-modal, pre-emptive analgesia decreases the length of hospital stay following total joint arthroplasty. Orthopedics. 2009; 32: 167.

Holzer P: Non-analgesic effects of opioids: Management of opioid-induced constipation by peripheral opioid receptor antagonists: Prevention or withdrawal? Curr Pharm Des. 2012; 18: 6010-6020.

Holzer P, Ahmedzai SH, Niederle N, et al.: Opioid-induced bowel dysfunction in cancer-related pain: Causes, consequences, and a novel approach for its management. J Opioid Manag. 2009; 5: 145-151.

Lenz H, Raeder J, Hoymork SC: Administration of fentanyl before remifentanil-based anaesthesia has no influence on postoperative pain or analgesic consumption. Acta Anaesthesiol Scand. 2008; 52: 149-154.

Ueberall MA, Muller-Lissner S, Buschmann-Kramm C, et al.: The bowel function index for evaluating constipation in pain patients: Definition of a reference range for a non-constipated population of pain patients. J Int Med Res. 2011; 39: 41-50.

Leppert W: Role of oxycodone and oxycodone/naloxone in cancer pain management. Pharmacol Rep. 2010; 62: 578- 91.

Leppert W: Emerging therapies for patients with symptoms of opioid-induced bowel dysfunction. Drug Des Devel Ther. 2015; 9: 2215-2231.

Liu M, Wittbrodt E: Low-dose oral naloxone reverses opioid-induced constipation and analgesia. J Pain Symptom Manage. 2002; 23: 48-53.

Coluzzi F, Ruggeri M: Clinical and economic evaluation of tapentadol extended release and oxycodone/naloxone extended release in comparison with controlled release oxycodone in musculoskeletal pain. Curr Med Res Opin. 2014; 30: 1139-1151.

Lazzari M, Sabato AF, Caldarulo C, et al.: Effectiveness and tolerability of low-dose oral oxycodone/naloxone added to anticonvulsant therapy for noncancer neuropathic pain: An observational analysis. Curr Med Res Opin. 2014; 30: 555-564.

Ahmedzai SH, Nauck F, Bar-Sela G, et al.: A randomized, double-blind, active-controlled, double-dummy, parallel-group study to determine the safety and efficacy of oxycodone/naloxone prolonged-release tablets in patients with moderate/severe, chronic cancer pain. Palliat Med. 2012; 26: 50-60.

Cuomo A, Russo G, Esposito G, et al.: Efficacy and gastrointestinal tolerability of oral oxycodone/naloxone combination for chronic pain in outpatients with cancer: An observational study. Am J Hosp Palliat Care. 2014; 31: 867-876.

Schang JC, Devroede G: Beneficial effects of naloxone in a patient with intestinal pseudoobstruction. Am J Gastroenterol. 1985; 80: 407-411.

Smith K, Hopp M, Mundin G, et al.: Low absolute bioavailability of oral naloxone in healthy subjects. Int J Clin Pharmacol Ther. 2012; 50: 360-367.

Vondrackova D, Leyendecker P, Meissner W, et al.: Analgesic efficacy and safety of oxycodone in combination with naloxone as prolonged release tablets in patients with moderate to severe chronic pain. J Pain. 2008; 9: 1144-1154.

Simpson K, Leyendecker P, Hopp M, et al.: Fixed-ratio combination oxycodone/naloxone compared with oxycodone alone for the relief of opioid-induced constipation in moderate-to-severe noncancer pain. Curr Med Res Opin. 2008; 24: 3503-3512.

Dunlop W, Uhl R, Khan I, et al.: Quality of life benefits and cost impact of prolonged release oxycodone/naloxone versus prolonged release oxycodone in patients with moderate-to-severe non-malignant pain and opioid-induced constipation: A UK cost-utility analysis. J Med Econ. 2012; 15: 564-575.



  • There are currently no refbacks.