The Expanding Role of the COX Inhibitor/Opioid Receptor Agonist Combination in the Management of Pain

Drugs. 2020 Sep;80(14):1443-1453. doi: 10.1007/s40265-020-01369-x.


Pain management in both outpatient and inpatient settings demands a multidisciplinary approach entailing medical, physical and psychological therapies. Among these, multimodal analgesic regimens stand out as a promising treatment options. Cyclo-oxygenase (COX) inhibitor/opioid receptor agonist combinations hold great potential as effective pillars in the multimodal pain management by providing adequate analgesia with fewer safety risks due to COX inhibitors' opioid-sparing effect. Thus, these combinations, either freely or in fixed-dose formulation, offer a feasible option for the prescribing clinicians who seek to maximise therapeutic effect while simultaneously minimise adverse effects. The selection of the appropriate non-steroidal anti-inflammatory drug (NSAID) and opioid agent at optimal doses is essential. It should be tailored to the patients' analgesic necessities, and his/her gastrointestinal and cardiovascular risk, and potential concurrent aspirin use. Moreover, it should allow for addiction risk and the potential opioid-induced bowel dysfunction and constipation. To ensure an optimal match between the characteristics of the patient and the properties of the chosen medication, and to guide adequate and well-tolerated treatment decisions, it is of paramount importance to expand clinicians' knowledge of the currently available COX inhibitor/opioid receptor agonist combinations. This invited narrative review deals with the literature evidence covering the components of multimodal opioid-sparing analgesic regimens. Also, it provides insights into the clinically relevant choice criteria to ensure a patient-tailored analgesia.

Publication types

  • Review

MeSH terms

  • Analgesics, Opioid / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase Inhibitors / pharmacology*
  • Humans
  • Pain / drug therapy*
  • Pain / metabolism
  • Pain Management
  • Receptors, Opioid / agonists


  • Analgesics, Opioid
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Receptors, Opioid
  • Cyclooxygenase 1
  • Cyclooxygenase 2