Naloxone, naldemedine appear best for opioid-induced constipation after laxatives

A meta-analysis found naloxone to have the highest efficacy and safety of pharmacological therapies for opioid-induced constipation, and previous research has shown it to be cost-effective, study authors said.


Clinicians should consider naloxone and naldemedine for opioid-induced constipation when laxatives fail, a meta-analysis found.

Researchers included 27 randomized controlled trials of pharmacological therapies in opioid-induced constipation with a total of 9,149 patients. Trials had to report a dichotomous assessment of overall response to therapy, with a minimum duration of two weeks. Data were pooled using a random effects model, and efficacy and safety were reported as a pooled relative risk to summarize the effect of each comparison.

The mu-opioid receptor antagonists naloxone, naldemedine, alvimopan, and subcutaneous methylnaltrexone, as well as the prokinetic prucalopride, were all more effective than placebo for opioid-induced constipation. The above-listed peripherally acting mu-opioid receptors antagonists (PAMORA) have restricted access to the central nervous system and hence selectively antagonize the GI effects of opioids. The primary analysis defined no response as failure to achieve an average of three or more bowel movements per week with an increase of one or more bowel movements per week over baseline, or an average of three or more bowel movements per week. Results were published online by Gut on May 5.

The meta-analysis found naloxone to have the highest efficacy (relative risk [RR], 0.65; 95% CI, 0.52 to 0.80; P=0.84), and it was also the safest drug. When nonresponse to therapy was defined using failure to achieve an average of three or more bowel movements per week with an increase of one or more bowel movements per week over baseline, naldemedine was the most effective drug (RR, 0.66; 95% CI, 0.56 to 0.77; P=0.91) and alvimopan was second (RR, 0.74; 95% CI, 0.57 to 0.94; P=0.71).

The authors noted that fewer than half of all patients with opioid-induced constipation benefit from laxatives and said that this is especially important given the continued increase in opioid prescribing worldwide and in gastroenterology, because up to 20% of patients with chronic abdominal pain disorders will be given opioids.

“All of this, together with evidence from the pharmacoeconomic literature demonstrating that naloxone is highly likely to be cost-effective, lends weight to either naloxone or naldemedine being the clinician's first choice of pharmacological therapy for [opioid-induced constipation] when laxatives fail,” the researchers wrote.