Managing opioid-induced constipation.

Abstract

in depth. Nursing professionals are critical for identifying constipation in patients using opioids and ensuring that these simple measures to alleviate distress and improve quality of life are implemented effectively. Where simple laxatives are insufficient to relieve OIC, a newer, more-expensive laxative approved for treating chronic constipation (i.e., lubiprostone or prucalopride) or an opioid antagonist should be considered. Lubiprostone stimulates intestinal fluid and electrolyte secretion by activating type 2 chloride channels. While lubiprostone is approved for treating refractory constipation in the USA and EU, it is only licensed for treating OIC in noncancer pain in the former. Prucalopride, a selective 5-HT4 agonist, is approved for treating refractory constipation in the UK, but not in the USA. These agents are modestly effective in treating OIC associated with non-cancer pain. The endpoints varied across studies precluding a comparison of their efficacy. Because the studies compared these drugs to placebo, the incremental benefit of these drugs over simple laxatives is unknown. Finally, their efficacy in OIC related to cancer pain is unknown. Of the μ-opioid-receptor antagonists used to treat OIC, some (i.e., naloxegol, methylnaltrexone) have peripheral effects only. Others (i.e., naloxone) also have central effects. The central effects may predispose to opioid withdrawal and reduce analgesia in some patients. Naloxegol comprises naloxone conjugated with polyethylene glycol, reducing its ability to cross the blood–brain barrier. Compared with placebo, the number needed to treat (NNT) for treating OIC with oral naloxegol (25 mg) in adults with chronic noncancer pain is approximately 7. In the USA, the approved indication for naloxegol use is OIC in non-cancer pain. In the EU, the approved indication is OIC in adult patients who have had an inadequate response to laxatives. In contrast to naloxegol, methylnaltrexone, is available only as a subcutaneous injection, and is essentially approved for treating OIC in patients with chronic non-cancer pain or advanced illness receiving palliative care in the USA and EU. In the pivotal study (Thomas et al, 2008) conducted in patients with an advanced illness (60% had cancer), 48% treated with a single dose of methylnaltrexone (0.15 mg/kg) versus 15% of placebo-treated U p to one third of the population in the western world report chronic pain. Pain causes distress and disability and has adverse socioeconomic consequences. Opioids are effective and have a favourable risk–benefit profile in conditions associated with acute pain or end-of-life pain. However, the widespread use of opioids, particularly newer semi-synthetic and synthetic opioids, for chronic non-cancer pain, has fuelled a crisis of iatrogenic opioid abuse, addiction, side effects, overdoses, and deaths, with no demonstrable reduction in the burden of chronic pain (Ballantyne and Sullivan, 2015). In the context of these opioid prescribing patterns, opioid-induced constipation (OIC) is common, does not decrease over time, compromises patient satisfaction with analgesic treatment, and limits opioid use (Camilleri et al, 2014). In a population-based survey (Cook et al, 2008), 57% of individuals with chronic non-cancer pain using opioids experienced constipation that they associated with opioid treatment. Moreover, 33% reported constipation as their most bothersome symptom. It is therefore crucial to ask patients on opioids about their bowel habits—not only stool frequency, but also other symptoms of constipation—and elicit changes in bowel patterns. When dealing with OIC, it is prudent to assess whether it is appropriate to use opioids to manage pain, and to discontinue them if not. The long-term use of opioids in patients with non-cancer non-palliative pain (e.g. chronic abdominal pain, fibromyalgia) should be strongly discouraged. Alternatives to opioids —nonopioid analgesics, antidepressant or antiepileptic medications in patients with neuropathic pain, and non-pharmacological adjuncts (e.g. meditation, cognitive behavioural therapy, and neurostimulators)—should be considered. If opioids are essential, anecdotal experience