NICE - naldemedine for treating opioid - induced constipation

Naldemedine is recommended, within its marketing authorisation, as an option for treating opioid-induced constipation in adults who have had laxative treatment.

• treatment of opioid-induced constipation depends on whether the opioid is the only cause of the constipation (pure opioid-induced constipation) or if there are other contributing factors (mixed aetiology constipation)
• treatment may include a peripherally acting mu-opioid receptor antagonist (PAMORA) alone. But, commonly a PAMORA and a conventional laxative are used together
• Naldemedine is an oral PAMORA for adults who have had laxative treatment

Notes:

• opioid receptors are present in the gastrointestinal tract - when opioids bind to these receptors they can disrupt normal gastrointestinal function, usually resulting in opioid-induced constipation
  • treatment for opioid-induced constipation could be a single treatment with a peripherally acting mu-opioid receptor antagonist (PAMORA) such as oral naloxegol or subcutaneous methylnaltrexone. But it commonly involves a combination of a PAMORA and a conventional laxative
  • Naldemedine is an alternative oral PAMORA taken as a single daily dose
  • estimated that over 80% of patients with cancer pain will have opioid-induced constipation, while the prevalence is likely to be lower in patients with non-cancer pain
  • in clinical practice, many patients taking a PAMORA have mixed aetiology constipation and so need a combination treatment to target the different causes of constipation
  • expert opinion stated that a key benefit of a PAMORA is that patients can have a normal stool, while those taking conventional laxatives often experience a continual back and forth of being constipated and then having diarrhoea. This is a huge burden for both patients and carers in terms of continually managing bowel function
• a review notes that given the relatively modest improvement in spontaneous bowel movements and the absence of evidence comparing this µ-opioid receptor antagonist directly with other interventions, it is likely to have a limited role in clinical practice (2)

Reference:

• NICE (September 2020). Naldemedine for treating opioid-induced constipation
• Naldemedine for opioid-induced constipation. Drug and Therapeutics Bulletin 2022;60:39-43