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Therapeutic opioid induced constipation — Clinical Guidelines

Overview

Opioid-induced constipation (OIC) is a common adverse effect of opioid therapy, significantly impacting patient quality of life and often resistant to traditional laxative treatments. 6 10

Diagnosis

Symptoms include decreased bowel movement frequency, hard stools, straining, and abdominal discomfort. 6

No specific diagnostic tests; clinical assessment is key. 6

Grading systems often based on Rome criteria for functional constipation adapted for OIC context. 6

Management

First-line treatments:

- Polyethylene glycol (PEG) and sennosides (e.g., PEG 13-16.5 g/day, sennosides 15-30 mg/day). 3 - Stool softeners and dietary modifications (increased fiber intake). 10

Adjunctive treatments:

- Peripherally acting μ-opioid receptor antagonists: - Methylnaltrexone bromide (8 mg subcutaneously every 24-48 hours). 6 10 13 15 - Naldemedine (0.1-0.2 mg orally daily). 2 - Naloxegol (12.5-25 mg orally daily). 7 - Neostigmine (low doses subcutaneously for refractory cases). 12

Special Populations

Elderly: Increased risk and complexity in management; careful monitoring and dose adjustment of laxatives and adjunctive therapies are crucial. 14

Advanced Illness/Hospice Patients: Methylnaltrexone is particularly effective in patients unresponsive to standard laxatives. 5 13

Key Recommendations

Initiate treatment with polyethylene glycol or sennosides for opioid-induced constipation, adjusting doses based on efficacy and tolerability. (Evidence: Moderate 3)

Consider peripherally acting μ-opioid receptor antagonists like methylnaltrexone for patients unresponsive to first-line laxatives, especially in advanced illness settings. (Evidence: Strong 6 13)

Monitor elderly patients closely due to increased susceptibility to adverse effects and consider individualized treatment plans. (Evidence: Moderate 14)

References

1 Mercadante S. A peripheral opioid antagonist for treating urinary retention induced by opioids: A case report. Palliative medicine 2022. link 2 Kanbayashi Y, Amaya F, Ueno H, Tabuchi Y, Ishikawa T, Takayama K et al.. Factors affecting the effect of naldemedine for opioid-induced constipation: a single-institution, retrospective analysis. Die Pharmazie 2021. link 3 Hawley P, MacKenzie H, Gobbo M. PEG vs. sennosides for opioid-induced constipation in cancer care. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 2020. link 4 Kim HJ, Jeong HE, Bae JH, Baek YH, Shin JY. Characteristics and trends of spontaneous reporting of therapeutic ineffectiveness in South Korea from 2000 to 2016. PloS one 2019. link 5 Sera L, McPherson ML. Management of Opioid-Induced Constipation in Hospice Patients. The American journal of hospice & palliative care 2018. link 6 Mozaffari S, Nikfar S, Abdollahi M. Methylnaltrexone bromide for the treatment of opioid-induced constipation. Expert opinion on pharmacotherapy 2018. link 7 Jones R, Prommer E, Backstedt D. Naloxegol: A Novel Therapy in the Management of Opioid-Induced Constipation. The American journal of hospice & palliative care 2016. link 8 O'Brien T. The attractiveness of opposites: agonists and antagonists. Journal of pain & palliative care pharmacotherapy 2015. link 9 Siemens W, Gaertner J, Becker G. Advances in pharmacotherapy for opioid-induced constipation - a systematic review. Expert opinion on pharmacotherapy 2015. link 10 Rauck RL. Treatment of opioid-induced constipation: focus on the peripheral μ-opioid receptor antagonist methylnaltrexone. Drugs 2013. link 11 Licup N, Baumrucker SJ. Methylnaltrexone: treatment for opioid-induced constipation. The American journal of hospice & palliative care 2011. link 12 Papa P, Turconi L. Neostigmine for the treatment of gastrointestinal atony: a report of one case. Journal of palliative medicine 2011. link 13 Chamberlain BH, Cross K, Winston JL, Thomas J, Wang W, Su C et al.. Methylnaltrexone treatment of opioid-induced constipation in patients with advanced illness. Journal of pain and symptom management 2009. link 14 Hayes BD, Klein-Schwartz W, Gonzales LF. Causes of therapeutic errors in older adults: evaluation of National Poison Center data. Journal of the American Geriatrics Society 2009. link 15 Portenoy RK, Thomas J, Moehl Boatwright ML, Tran D, Galasso FL, Stambler N et al.. Subcutaneous methylnaltrexone for the treatment of opioid-induced constipation in patients with advanced illness: a double-blind, randomized, parallel group, dose-ranging study. Journal of pain and symptom management 2008. link 16 Mercadante S, Ferrera P, Villari P, Arcuri E. Hyperalgesia: an emerging iatrogenic syndrome. Journal of pain and symptom management 2003. link00258-6) 17 . Risk assessment of drugs, biologics and therapeutic devices: present and future issues. Pharmacoepidemiology and drug safety 2003. link 18 Mercadante S, Villari P, Fulfaro F. Rifampicin in opioid-induced itching. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 2001. link 19 Katcher J, Walsh D. Opioid-induced itching: morphine sulfate and hydromorphone hydrochloride. Journal of pain and symptom management 1999. link00115-8)

Therapeutic opioid induced constipation