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The therapeutic action of opioid analgesics is compromised by peripheral adverse effects, among which constipation is the most disabling, as laxatives often fail to provide satisfactory relief.1 To address this problem, opioid receptor antagonists with limited systemic bioavailability (retarded naloxone) or a peripherally restricted site of action (alvimopan, methylnaltrexone) have been developed. Their use in managing opioid-induced constipation (OIC), however, is limited by narrow indication and subcutaneous administration (methylnaltrexone), approval only for short-term use because of safety concerns (alvimopan) or a fixed combination of retarded naloxone with oxycodone.2 Naloxegol is a peripherally acting μ-opioid receptor antagonist under development as an …