Enteral Naloxon Safely Prevents Opioid Induced Constipation... Now also Confirmed in the NEJM

It's not really the biggest news, but it's in the NEJM and it lines up with several publications looking at preventing opioid induced constipation with enteral naloxone. The article is remarkable in that sort of way as it represents a quite big double blinded study, while many publications before had a rather descriptive character. It has been shown before, that enteral naloxone helps reduce constipation when administered in conjunction with oxycodone. 

Interestingly enteral administration of naloxone blocks opioid action at the intestinal receptor level, but has a low systemic bioavailability due to marked hepatic first pass metabolism. In this study the investigators used naloxegol which is a PEGylated form of naloxone. This means that polyethylene glycol (PEG) polymer chains were covalently attached to the naloxone molecule.

Chey WD et al. now basically present 2 double blinded studies including 625 patients in one and 700 patients in the other. Outpatients with non-cancer pain who were already getting opioids and experienced constipation were randomly assigned to receive either enteral naloxone (12.5mg or 25mg) or placebo. Primary endpoint was clinical response after twelve weeks defined as more than 3 bowel motions per week or an increase in bowel motions. Result: Enteral naloxone significantly reduced time to to the first post dose spontaneous bowel motion and increased the frequency of bowel motions. It is important to note that enteral naloxone did not reduce opioid mediated analgesia.

Enteral naloxone should be considered in prevention or treatment of opioid induced constipation, also in the ICU.

Chey WD et al. N Engl J Med. (2014)

Webster et al. Aliment Pharmacol Ther 2014 Oct;40(7):771-9

This might also be of interest:

Meissner et al. Crit Care Med. 2003 Mar;31(3):776-80, Enteral naloxone reduces gastric tube reflux and frequency of pneumonia in critical care patients during opioid analgesia.

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