Naloxone, naldemedine, and alvimopan best options for treatment of opioid-induced constipation

Reference

Luthra P, Burr NE, Brenner DM, Ford AC. Efficacy of pharmacological therapies for the treatment of opioid-induced constipation: systematic review and network meta-analysis. Gut 2019;68:434-444.

Synopsis

The authors of this network meta-analysis searched the usual databases to identify randomized controlled trials that compared drug therapies for OIC with each other or placebo in adults. Studies had to be at least 2 weeks in duration, and had to provide a measure of overall response (ie, "significantly improved" vs "not significantly improved"), not just a symptom score. The authors identified 27 studies, most reporting on mu-opioid receptor antagonists like naloxone or methylnaltrexone, and all comparing a drug to placebo. Only 11 were judged to be at low risk of bias. The outcome of failure to achieve either an average of at least 3 bowel movements (BMs) per week with an increase of at least 1 BM per week over baseline or an average of at least 3 BMs per week was reported by 22 studies, 9 of which were at low risk of bias. Naloxone (2 studies), naldemedine (5 studies), and alvimopan (3 studies) all had a relative risk of 0.65 to 0.67 (a relative risk less than 1 means they were less likely to fail to achieve the desired outcome). Methylnaltrexone SC, prucalopride, and bevenopran appeared in 2 studies each with a relative risk of 0.74 to 0.78. Three drugs did not significantly improve outcomes: naloxegol (Movantik), methylnaltrexone oral, and lubiprostone. In the network meta-analysis comparing each drug indirectly to each other drug, the most favorable results were seen for naloxone, naldemedine (Symproic), and alvimopan (Entereg), which are all mu-opioid receptor antagonists. Regarding safety, naloxone was ranked highest and lubiprostone was ranked lowest.