1. All patients should commence lifestyle measures to help manage opioid-induced constipation with the understanding that these measures alone are unlikely to be sufficient3,7

A dietary history will help determine whether there is sufficient fibre in the diet in the form of cereals, grains, fruit and vegetables. Increasing dietary fibre to the recommended daily intake of approximately 30 g or the use of fibre supplements such as psyllium should help in those patients who are having insufficient fibre. Adequate daily fluid intake (2 L/d)14 is also important to optimise the benefit of fibre. However, taking too much fibre can result in bloating or flatulence in many patients without relieving constipation and may even aggravate it. Similarly, merely increasing the daily fluid intake in the absence of adequate fibre will not improve constipation.15

Increasing physical activity can promote colonic motility and should be encouraged. Also advise the patient to establish a regular bowel routine, e.g. by opening bowels after meals when colonic transit is maximal.15

2. Use of pharmacotherapies should be based on the clinical actions of opioids

Laxatives are often used as the first therapy to manage opioid-induced constipation, however the key actions of opioids on the GI tract (dys-coordinated motility, decreased secretions and sphincter dysfunction) are not targeted by laxatives and this is a reason why laxatives are often ineffective.7 Approximately 50% of patients may not achieve a satisfactory response with laxative therapy.16  

There is a lack of data about which laxative is most effective in managing opioid-induced constipation.14,17  The commonest laxative regimes for opioid-induced constipation combine a stimulant laxative with a stool softener:3

  • Stimulant laxatives e.g. senna or bisacodyl increase GI muscle contractions to address slowed colonic transit3
  • Stool softeners act through one of three mechanisms to address dry hard stools, e.g.:3
    • Osmotic laxatives, e.g. polyethylene glycol or lactulose draw or retain water in the colon to hydrate the stools
    • Surfactants, e.g. docusate, are emulsifiers that facilitate the mixture of fats and water in faeces
    • Lubricants, e.g. mineral oil, delay the absorption of water from the colon to soften stools

Opioid antagonists whose actions are limited to the enteric opioid receptors are an alternative method for managing opioid-induced constipation.7 There are two options available in Australia, naloxone  (available in a combination with oxycodone in a modified-release tablet) or subcutaneous methylnaltrexone.18,19 Note, methylnaltrexone is only approved for use in the palliative care setting.19

The key to the effectiveness of an opioid antagonist is to have selective antagonism, only blocking the actions of the opioid in the GI tract and not systemically in order to preserve its analgesic activity.7 With oral naloxone this selectivity is achieved as naloxone undergoes extensive first-pass metabolism in the healthy liver. It has a low oral bioavailability with at least 97% being metabolised during first pass. In contrast, up to 87% of the opiate oxycodone passes into the circulation intact enabling it to reach the CNS where it exerts an analgesic effect.7,18 Modified-release oxycodone/naloxone has been shown to effectively prevent and manage opioid-induced constipation while maintaining effective analgesia in patients with both chronic non-cancer pain20,21 and chronic cancer pain.22,23

Methylnaltrexone does not cross the blood-brain barrier, hence it does not block the central analgesic actions of the co-administered opioid analgesic.7

The effectiveness of these two opioid antagonists has been confirmed by a meta-analysis. The number of patients who were needed to be treated (NNT) before one patient with opioid-induced constipation failed to respond to therapy was 4 (95% CI 3-5) for modified-release oxycodone/naloxone and was 3 (95% CI 2-10) for methylnaltrexone. As this is the number needed to treat for one patient to have unsuccessful therapy, a higher NNT equates to greater efficacy.24