Pharmacological management

Evidence summary

A systematic review of studies of lactulose (osmotic agent) as an aperient in a range of populations, including those with terminal illness, showed that lactulose was better than placebo for managing constipation. It is regarded as moderately effective, and often needs to be combined with a second agent. [1]

A systematic review of docusate (softener) in palliative care patients and based on small studies which were not of good quality, showed a small trend to increased stool frequency with the use of docusate. It is suggested that there is not sufficient evidence to justify its use. [1,2]

Senna was shown to be similar in terms of effectiveness and adverse effects to lactulose but is less expensive. [1]

The common practice of recommending a stimulant and a lubricant or softening laxative together as prophylaxis when prescribing opioids is supported by low level evidence. This comes from a prospective open label volunteer study of the role of combinations of laxatives in the management of opioid induced constipation. [3]

There are small studies of polyethylene glycol (macrogol) (osmotic agent) [1,4] in a palliative care population which suggest that it is moderately effective and has a better adverse effect profile than other oral laxatives. Polyethylene glycol has been used in the management of faecal impaction, and appears to be effective [3] although these studies were not focused on palliative care patients.

Opioid antagonists are finding a place in the management of opioid induced constipation. [5,6] Methylnaltrexone is an opioid antagonist specifically developed for treating opioid induced bowel dysfunction, which can be given subcutaneously. Naloxone is now frequently prescribed in a combination preparation with a prolonged release preparation of oxycodone (Targin). Systematic reviews have concluded that peripherally acting opioid antagonists may be effective in opioid induced constipation, [1,6] but further evidence of safety and efficacy are still needed for methylnaltrexone.

There is little evidence to support the use of other oral laxatives, and none regarding the effectiveness of rectally applied agents. [1] Guidelines have been developed for the management of constipation in advanced cancer which may support clinical decision making in a palliative setting. [3]

Practice implications

• Prescribing of laxatives continues to be based on expert opinion. The principles of prescribing laxatives in a palliative care population focus on prevention of constipation. Co-prescription of either a stimulant (senna is commonly used in Australia) plus a softening or lubricant laxative such as docusate (eg Coloxyl), or increasingly, prescription of macrogol (Movicol), are commonly suggested for patients on opioids. [3] Coloxyl alone is not recommended. [1]
• The role of mu-opioid antagonists in the palliative care setting needs further research. [6]
• Educating patients about the relationship of constipation to opioids, and the need for laxative co-therapy, is also an essential part of opioid prescribing.
• Regular assessment for constipation, and of adverse effects of laxative therapy (pain, bloating, flatulence), is an essential part of ongoing care.
• It is important to consider a patients’ own preferences in the choice of laxative [3]