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Methylnaltrexone for opioid-induced constipation in patients at the end of life.

International Journal of Palliative Nursing 2015, Vol 21, No 4 © 2 01 5 M A H ea lth ca re L td Opioids are frequently used for pain management, especially in patients with advanced disease who are at the end-of life. Regrettably, opioid use often comes with some unwanted gastrointestinal side-effects. Constipation is a common concern with opioid use and can be present in up to 50% of patients taking opioids for pain management (Hellwig, 2013). Constipation can lead to straining, bloating, abdominal distention, discomfort and pain. When constipation becomes a problem, too frequently the first solution becomes to reduce the amount of opioid being given, which can lead to worsening pain and ultimately poorer quality of life. Healthcare providers often underestimate the impact opioid use has on bowel function and the ultimate effect it has on quality of life. Constipation is typically defined as stool passage being difficult, incomplete, or deficient and occurring less than three times per week (Kumar et al, 2014), and can be assessed using several tools (McCrea, 2008). A key to preventing or managing opioid-induced constipation is to initiate a bowel regimen once a patient begins taking any opioid. While other opioid side-effects, such as sedation, tend to decrease over time, unfortunately constipation will continue to be a problem and worsen if not addressed (Santucci, 2007). Although there are different approaches to managing constipation, first-line treatment options can be categorised as either non-pharmacologic or pharmacologic (Figure 1). Opioids modulate pain by binding to specific receptors throughout the central and peripheral nervous systems. Primary analgesia occurs at the mu (μ) receptor site, which is also located in the gastro-intestinal tract. Once activated, μ receptor sites can inhibit peristalsis and normal gut function, resulting in constipation. Opioids, however, have variances in the way they bind to specific receptors and patients may respond to them differently. Each opioid can cause different side-effects and varying degrees of these, thus rotating opioids is another strategy used to manage unwanted side-effects, such as constipation. Understanding how to convert from one opioid to another using appropriate equi-analgesia is vital to achieve adequate pain management while avoiding over or under dosing. The use of non-selective μ-opioid antagonists (e.g. low dose naloxone) may have some effectiveness in reversing the effect of the opioid and thereby reducing the unwanted side-effect, however, these medications cross the blood–brain barrier and may cause a reversal of analgesia and/or withdrawal, and therefore are not recommended (Kurz and Sessler, 2003). Rather, when first-line medications fail in the management of opioid-induced constipation, a trial of μ-opioid antagonists should be considered. Methylnaltrexone (trade name Relistor) is a positively charged derivative of naltrexone (a μ-opioid antagonist) that does not cross the blood–brain barrier, making it a μ-opioid selective antagonist (Camilleri, 2011). It was approved for use specifically for patients with advanced disease receiving palliative care that develop opioid induced constipation refractory to standard first-line therapies. Safety and efficacy has been established by randomised, double-blind placebo-controlled studies (Yuan et al, 1996; Yuan et al, 2002; Thomas et al, 2008). It binds to μ receptors in the gut, thus blocking the effect of opioids without compromising patient analgesia or causing opioid-withdrawal symptoms. It is administered via a subcutaneous injection, usually in the abdomen, upper thigh or upper arm. Subcutaneous methylnaltrexone is rapidly absorbed with peak plasma concentrations attained within 0.5 hours after administration, terminal half-life is approximately 8 hours and it is excreted primarily unchanged in the urine and faeces (Salix Pharmamceuticals, 2010). Doses, based on body-weight, can be given every other day, as needed, with a maximum of one dose per 24 hours (Table 1). Methylnaltrexone is largely well tolerated in patients with advanced disease at the end of life who experience opioid-induced constipation, but use is contraindicated in patients with known or suspected gastrointestinal obstruction or patients who are at risk of developing an obstruction (Salix Pharmaceuticals, Commentary