Beyond Pain Control: Understanding and Managing Opioid-Induced Constipation

Opioid-induced constipation (OIC) remains one of the most challenging adverse effects of opioid therapy. Unlike other opioid-related adverse effects, such as nausea or fatigue, which can diminish over time, constipation tends to be an ongoing challenge as long as patients take opioid medications.

Up to 87% of individuals who take opioids for a long period time say they have OIC. Side effects can interfere with daily life, reduce quality of life, and even cause patients to reduce the dosage or discontinue the drug completely.¹ The underlying cause has to do with activation of peripheral μ‑opioid receptors in the gastrointestinal tract, which slows the stomach from clearing. All of this leads to hard, dry stools and constipation.

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The first steps to managing this usually include nonpharmacological options, such as eating more fiber, drinking enough water, and increasing physical activity. Pharmacological support often starts with OTC agents, like water-holding laxatives (e.g., polyethylene glycol and lactulose) and stimulant laxatives (e.g., bisacodyl and senna). While these agents may work well for normal slow bowels, they often don't do enough for OIC because they do not address the underlying cause.²

When symptoms persist despite these measures, the next step involves peripherally acting μ‑opioid receptor antagonists (PAMORAs), which directly target the cause of OIC. These act on the μ-opioid receptors in the gut, which are a key cause of OIC.³ PAMORAs like methylnaltrexone (Relistor; Salix), naloxegol (Movantik; Valinor), and naldemedine (Symproic; Collegium) work by blocking these receptors in the gut.^4,5

Methylnaltrexone, available as a pill or injection, was the first approved in this group. Naloxegol, an oral medication for individuals on long-term opioid medication for non-cancer-related pain, also works well and is supported by a significant body of evidence.⁶ Naldemedine, another oral PAMORA, has been well-established in individuals with cancer or other sources of pain, with established efficacy and safety.^7,8

Despite the therapeutic benefits of PAMORAs, clinicians and pharmacists must be vigilant about their contraindications and associated risks. The primary concern is the potential for gastrointestinal perforation, particularly in patients with known or suspected obstruction, compromised mucosal integrity, or advanced gastrointestinal disease. A comprehensive review, including PubMed literature and the FDA’s Adverse Event Reporting System (FAERS), identified rare but life‑threatening cases of gastrointestinal (GI) perforation associated with both laxatives and PAMORAs, emphasizing that laxation may disrupt already vulnerable bowel linings.⁹ This real‑world evidence underscores the importance of informed selection and cautious prescribing.

Role of the Pharmacist

Pharmacists have a key role to play early on when managing OIC. As accessible health experts, they are important in spotting patients at risk, advising on nonpharmacologic management options, and ensuring patients follow treatment plans. Pharmacists can advise patients initiating opioid medications about the chance of constipation and the importance of initiating preventive steps right away, rather than waiting for signs to emerge. They can also aid in choosing the right OTC treatments based on other health concerns, prescribed medications, and patient-specific factors.

Pharmacists must also identify any contraindications for patients prescribed PAMORAs, including past surgeries, diagnoses, or potential GI blocks. Signs such as stomach cramps or diarrhea should also be closely monitored, and patients should be educated about when to stop taking the medication and see a physician.

Because they see patients often, pharmacists are also well-positioned to monitor treatment effectiveness. By asking questions like, "How have your trips to the bathroom been since you started this new drug?" they can identify problems that patients haven't talked about and initiate timely interventions. Pharmacists can keep an eye on how well the treatment works, suggest any dose changes, and help switch treatments if needed.

Conclusion

Effectively managing OIC is essential for patients taking opioid medications—not just for patient comfort, but also for maintaining adherence and preventing serious complications like GI perforation. Pharmacists, with their pharmacotherapy expertise, accessibility, and patient rapport, are perfectly situated to lead this effort, from educating patients and recommending safe treatment pathways to monitoring responses and identifying challenges or concerns. By integrating evidence‑based strategies, vigilant monitoring, and patient engagement, pharmacists can dramatically decrease OIC’s burden and uphold both comfort and safety in opioid care.

REFERENCES

1. Ducrotté P, Milce J, Soufflet C, Fabry C. Prevalence and clinical features of opioid-induced constipation in the general population: A French study of 15,000 individuals. United European Gastroenterol J. 2017;5(4):588-600. doi:10.1177/2050640616659967

2. What You Can Do About Opioid Induced Constipation. Verywell Health. https://www.verywellhealth.com/opioid-induced-constipation-treatment-4153814

3. Squeo F, Celiberto F, Ierardi E, et al. Opioid-induced constipation: Old and new concepts in diagnosis and treatment. Journal of Neurogastroenterology and Motility. 2024;30(2):131-142. doi:10.5056/jnm23144

4. Pergolizzi Jr JV, Christo PJ, LeQuang JA, Magnusson P. The Use of Peripheral μ-Opioid Receptor Antagonists (PAMORA) in the Management of Opioid-Induced Constipation: An Update on Their Efficacy and Safety. Drug Design, Development and Therapy. 2020;14:1009-1025. doi:10.2147/DDDT.S221278

5. Costanzini A, Ruzza C, Neto JA, et al. Pharmacological characterization of naloxegol: In vitro and in vivo studies. European Journal of Pharmacology. 2021;903:174132. doi:10.1016/j.ejphar.2021.174132

6. Nero R, Allen B, Hailu K, Noor R, Theiss K. Impact of oral naloxegol vs subcutaneous methylnaltrexone in treatment of opioid-induced constipation in the hospital setting. 2022;80(Supplement_2):S70-S76. doi:10.1093/ajhp/zxac356

7. Hanson B, Siddique SM, Scarlett Y, Sultan S; American Gastroenterological Association Institute Clinical Guidelines Committee. American Gastroenterological Association Institute Technical Review on the Medical Management of Opioid-Induced Constipation. Gastroenterology. 2019;156(1):229-253.e5. doi:10.1053/j.gastro.2018.08.018

8. Hamano J, Higashibata T, Kessoku T, et al. Naldemedine for Opioid-Induced Constipation in Patients With Cancer: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial. Journal of Clinical Oncology. Published online September 10, 2024. doi:10.1200/jco.24.00381

9. Mehta N, Laitman AP, Brookfield RB, Harris LA. Treatment of Opioid-Induced Constipation: Inducing Laxation and Understanding the Risk of Gastrointestinal Perforation. J Clin Gastroenterol. 2025;59(6):491-496. Published 2025 Jul 1. doi:10.1097/MCG.0000000000002185