An inadequate response is defined as opioid-induced constipation symptoms of at least moderate severity in at least one of the four stool symptom domains — incomplete bowel movements, hard stools, straining, or false alarms — while taking at least one laxative class for at least 4 days during the past 2 weeks.

Prevailing guidelines do not define a maximal daily dose limit for combination laxatives (osmotic/stool softeners targeting stool consistency plus a stimulant targeting bowel transit) that would meet the criteria for an adequate trial before a PAMORA should be considered.

While the Palliative Care Formulary defines the maximum permissible daily dosing for each laxative class, in practice, PAMORAs may have been prescribed before this threshold is reached.

A mixed aetiology for the underlying constipation (opioid induced constipation may be accompanied with other etiologies such as reduced oral intake and reduced colonic transit, secondary to carcinomatosis), might mean that PAMORAs are prescribed in addition to stimulant laxatives in most cases.

The use of PAMORAs may also be necessitated by practical reasons — particularly the requirement of maintaining stool consistency when higher doses of conventional laxative classes risk causing loose stools.

Recognizing that a mechanistic paradox exists, and is being driven by the necessity of using high doses of conventional laxatives, might mean that the occurence of diarrhoea becomes a foreseeable consequence. This mechanistic paradox arises due to the failure of conventional laxatives to address the mechanism underlying OIC directly, without overwhelming the bowel’s capabilities to absorb fluids or risking potentially deleterious hypermotility. PAMORAs, then might be better suited as targeted adjuncts rather than replacements for conventional laxatives.

References

National Institute for Health and Care Excellence. (2015, reviewed 2021). Naloxegol for treating opioid-induced constipation (Technology Appraisal Guidance TA345). NICE. https://www.nice.org.uk/guidance/ta345

National Institute for Health and Care Excellence. (2020). Naldemedine for treating opioid-induced constipation (Technology Appraisal Guidance TA651). NICE. https://www.nice.org.uk/guidance/ta651

Wilcock, A., Howard, P., & Charlesworth, S. (Eds.). (2022). Palliative care formulary (8th ed.). Pharmaceutical Press / palliativedrugs.com. ISBN 9780857114372. https://www.palliativedrugs.com

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