Oxycodone/Naloxone: Role in Chronic Pain Management, Opioid-Induced Constipation, and Abuse Deterrence

Abstract

The use of opioids in the treatment of chronic pain is widespread; the prevalence of specific opioids varies from country to country and depends on product availability, national formulary systems, and provider preferences. Patients often receive opioids for legitimate treatment of pain conditions, but on the opposite side of the spectrum, nonmedical use of opioids is a significant public health concern. Opioids are associated with several side effects, and constipation is the most commonly reported and persistent symptom. Unlike some adverse effects associated with opioid use, tolerance does not develop to constipation. Opioid-induced constipation (OIC) is the most prevalent patient complaint associated with opioid use and has been associated with declines in various quality of life measures. OIC can be extremely difficult for patients to tolerate and may prompt patients to decrease or discontinue opioid treatment. Current management strategies for OIC are often insufficient. A prolonged-release formulation of oxycodone/naloxone (OXN) has been investigated for the treatment of nonmalignant and cancer pain and mitigation of OIC, and evidence is largely favorable. Studies have demonstrated the capability of OXN to alleviate OIC while maintaining pain control comparable to oxycodone-only regimens. There is insufficient evidence for OXN efficacy for patients with mild OIC or patients maintained on high doses of opioids, and use in these populations is controversial. The reduction of costs associated with OIC may provide overall cost effectiveness with OXN. Additionally, the presence of naloxone may deter abuse/misuse by those seeking to misuse the formulation by modes of administration other than oral ingestion. Most studies to date have occurred in European countries, and phase 3 trials continue in the United States. This review will include current therapeutic options for pain and constipation, unique characteristics of OXN, evidence related to use of OXN and its place in therapy, discussion of opioid abuse/misuse, and various abuse-deterrent mechanisms, and areas of continuing research.Electronic supplementary materialThe online version of this article (doi:10.1007/s40122-014-0026-2) contains supplementary material, which is available to authorized users.

Opioid-induced constipation

“…This OXN sustained release formulation is supplied in the following combinations of oxycodone/naloxone: 5/2.5, 10/5, 20/10, 40/20 mg. The 10/5 mg q12h is the usual starting dose with maximum daily dose limit of 80/ 40mg [48].…”

Increases in controlled‐release oxycodone utilisation following the subsidy of oxycodone with naloxone formulations: An Australian population‐based study

“…Oxycodone with naloxone controlled‐release (CR) tablets are fixed‐dose combination products with equivalent analgesia and similar adverse effects to single‐ingredient oxycodone CR tablets of the same strength . The addition of naloxone, an opioid antagonist that blocks opioid receptors in the gut, reduces but does not eliminate constipation, a common adverse effect of opioid therapy . Oxycodone/naloxone CR is only one of a growing number of new opioid products marketed in recent years …”

Oxycodone/Naloxone PR: A Review in Severe Refractory Restless Legs Syndrome

“…Because of its very low oral bioavailability, naloxone effectively blocks the undesired activity of oxycodone at opioid receptors in the gut, but not the desired (e.g. analgesic) activity of oxycodone at opioid receptors within the CNS [20][21][22].…”