Treatment of Opioid-Induced Constipation: Inducing Laxation and Understanding the Risk of Gastrointestinal...

Patients receiving opioid analgesics may experience constipation [ie, opioid-induced constipation (OIC)], require treatment to induce laxation, and may be at risk for gastrointestinal perforation, an uncommon but potentially life-threatening condition. Management of OIC includes treatment with over-the-counter laxatives and peripherally acting μ-opioid receptor antagonists (PAMORAs; methylnaltrexone, naloxegol, naldemedine). In patients receiving treatment for OIC, gastrointestinal perforation may result from the laxation process, causing disruption of the gastrointestinal lining that may already have compromised integrity. A PubMed literature review and a search of the US Food and Drug Administration Adverse Event Reporting System database identified several cases of gastrointestinal perforation (life-threatening or with mortality) across the range of agents administered for the treatment of OIC or other constipation types. Methylnaltrexone in the subcutaneous form was the first PAMORA approved for OIC. Its real-world use in the ∼6 years before the availability of another OIC-indicated PAMORA helped establish the adverse-event profile of the class, and experience has been gained in identifying and treating appropriate patient populations. Class labeling of PAMORAs includes a contraindication in patients with known or suspected gastrointestinal obstruction or increased risk of recurrent obstruction. Appropriate patient selection during laxation therapy for OIC, regardless of treatment plan, involves consideration of the overall risk versus benefit in patients at increased risk of perforation due to comorbid medical conditions, concurrent medications, or recent gastrointestinal procedures. After initiating treatment for OIC, clinicians should assess the effectiveness of laxation therapy and carefully monitor for signs of gastrointestinal perforation.