Safety of Naldemedine for Opioid-Induced Constipation - A Systematic Review and Meta-Analysis.

Naldemedine is a peripheral acting µ-opioid receptor antagonist approved by the Food and Drug Administration to treat opioid-induced constipation. Concerns about side effects like opioid withdrawal prevent its widespread use, especially for cancer patients. We performed this systematic review and meta-analysis to evaluate existing safety data of naldemedine treating opioid-induced constipation following the PRISMA guidelines. We searched PubMed and the Cochrane Library on April 16th 2024 to identify studies evaluating naldemedine treatment among patients with opioid-induced constipation. Our analysis found no differences between groups comparing naldemedine therapy with placebo-control for treatment-emergent adverse events (OR = 1.06; 95%-CI: 0.91-1.24), serious adverse events (OR = 1.02; 95%-CI: 0.76-1.38). We found no increased risk for opioid withdrawal, while an increased risk for gastrointestinal disorders (OR = 2.08; 95%-CI: 1.72-2.51), particularly higher incidences of diarrhea (OR = 2.44; 95%-CI: 1.81-3.29) and abdominal pain (OR = 3.31; 95%-CI: 2.16-5.06) were found. In the cancer subgroup, treatment-emergent and serious adverse events were more frequent. However, no increased risk for opioid withdrawal was observed. This analysis confirms naldemedine's overall safety in treating opioid-induced constipation, with manageable gastrointestinal side effects. However, the higher adverse events in cancer patients require further investigation to ensure safe use in this population.