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We read with interest the recent systematic review and network meta-analysis on the efficacy of pharmacological treatment of opioid-induced constipation (OIC).1 The authors reviewed 27 randomised controlled trials (RCTs) involving 9149 patients and concluded that naloxone was the best drug in patients with OIC, followed by naldemedine. We believe that several factors impacted the appraisal of relative efficacy and deserve discussion especially in network meta-analyses with no head-to-head drug trials.
Distribution and potential for opioid withdrawal: Naloxone is a lipophilic, non-selective and competitive opioid receptor antagonist. The oral formulation of naloxone has a bioavailability of ~2%; however, it is widely distributed, has a narrow therapeutic index and the oral doses required to treat OIC can increase the risk of opioid withdrawal symptoms. On the other hand, peripherally acting mu-opioid receptor antagonists such as naldemedine and …
Contributors VC: review of the literature and writing the manuscript. MC: concept development, significant reviews and edits of the manuscript, senior author.
Competing interests MC has conducted research on naloxegol and alvimopan, and served as adviser on naldemedine and naloxegol with financial remuneration to his employer, Mayo Clinic, not to him personally.
Patient consent Not required.
Provenance and peer review Not commissioned; internally peer reviewed.