Naloxegol for Opioid-Induced Constipation
Introduction to Naloxegol
- The American Gastroenterological Association strongly recommends naloxegol 25 mg once daily as an effective treatment for laxative-refractory opioid-induced constipation in adults with chronic non-cancer pain, improving bowel function without compromising pain control 1, 2
Treatment Algorithm
- The American Gastroenterological Association recommends starting prophylactic stimulant laxatives when initiating opioid therapy, with the goal of one non-forced bowel movement every 1-2 days 3
- Naloxegol is indicated only after inadequate response to conventional laxatives 1, 2, 4
Efficacy Data
- 41.9% of patients on naloxegol 25 mg achieved response versus 29.4% on placebo, with response defined as ≥3 spontaneous bowel movements per week with an increase from baseline of ≥1 SBM/week for at least 9 of 12 weeks 5, 6, 7
- Naloxegol improves spontaneous bowel movement frequency and reduces straining during defecation 5
Safety Profile
- Common adverse effects of naloxegol include abdominal pain (17.8%), diarrhea (12.9%), nausea (9.4%), headache (9.0%), and flatulence (6.9%) 5
- Adverse events leading to discontinuation occur in approximately 9.4% of patients versus 4.2% on placebo 5
Mechanism of Action
- Naloxegol is a pegylated derivative of naloxone that blocks peripheral μ-opioid receptors in the gut, with pegylation increasing oral bioavailability and enhancing peripheral selectivity 1, 2
- Naloxegol acts as a substrate for P-glycoprotein transporter, limiting entry into the central nervous system, and does not cross the blood-brain barrier, preserving central opioid analgesia 1, 2, 4
FDA Approval Status
- Naloxegol was FDA-approved in 2014 as the first oral PAMORA for OIC in adults with chronic non-cancer pain 1, 2, 7
- Not FDA-approved for use in patients with OIC and active cancer pain 7