From the Guidelines
The best approach to manage opioid-induced constipation involves a stepwise strategy starting with preventive measures and progressing to pharmacological interventions as needed, with the most recent guidelines from 2023 recommending prevention with senna and treatment with magnesium-based products and laxatives such as bisacodyl, and peripherally acting mu-opioid receptor antagonists (PAMORAs) for refractory cases 1.
Key Considerations
- Prevention should begin when opioid therapy is initiated, including lifestyle modifications such as increased fluid intake and dietary fiber, and regular physical activity.
- First-line pharmacological treatment includes stimulant laxatives like senna or bisacodyl, often combined with stool softeners such as docusate sodium.
- If these are ineffective, osmotic laxatives like polyethylene glycol should be added.
- For refractory cases, PAMORAs such as methylnaltrexone, naloxegol, or naldemedine are recommended as they specifically target the mechanism of opioid-induced constipation without affecting pain control.
Mechanism of Action
- Opioids exert their gastrointestinal effects via k-receptors in the stomach and small intestine and m-receptors located in the small intestine and proximal colon, leading to increased tonic non-propulsive contractions, increased colonic fluid absorption, and stool desiccation.
- PAMORAs work by blocking opioid receptors in the gastrointestinal tract while not crossing the blood-brain barrier, thus maintaining analgesic effects.
Clinical Evidence
- The American Gastroenterological Association Institute Guideline on the Medical Management of Opioid-Induced Constipation recommends a stepwise approach to management, with prevention and treatment strategies based on the severity of constipation 1.
- The National Comprehensive Cancer Network (NCCN) Guidelines for Adult Cancer Pain recommend a stimulant laxative or polyethylene glycol with 8 oz of water 2 times daily, along with maintaining adequate fluid intake, for prophylaxis 1.
- A recent mixed-treatment comparison network meta-analysis found that subcutaneous methylnaltrexone was safe and effective for opioid-induced constipation, with no improvement regarding background pain using opioids 1.
From the FDA Drug Label
1.2 Opioid-Induced Constipation in Adult Patients with Chronic Non-Cancer Pain Lubiprostone is indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation.
2.1 Recommended Dosage The recommended oral dosage of Lubiprostone by indication and adjustments for patients with moderate (Child Pugh Class B) and severe (Child Pugh Class C) hepatic impairment are shown in Table 1.
Table 1 Recommended Dosage Regimen CIC and OIC | IBS-C 24 mcg twice daily | 8 mcg twice daily
The best approach to manage opioid-induced constipation is to use lubiprostone (PO) with a recommended adult dosage regimen of 24 mcg twice daily 2. It is essential to take lubiprostone orally with food and water, swallow capsules whole, and not break apart or chew.
- Key considerations:
- The effectiveness of lubiprostone in patients taking diphenylheptane opioids (e.g., methadone) has not been established.
- Patients should be aware of the possible occurrence of diarrhea during treatment and instructed to discontinue lubiprostone and contact their healthcare provider if severe diarrhea occurs.
- Nausea is a common adverse reaction, and concomitant administration of food with lubiprostone may reduce symptoms of nausea.
From the Research
Management of Opioid-Induced Constipation
The management of opioid-induced constipation (OIC) involves a multi-step approach, including non-pharmacological therapies, laxative therapies, and the use of peripherally acting μ-opioid receptor antagonists (PAMORAs) [ 3, 4,5,6,7 ].
Non-Pharmacological Therapies
- Lifestyle changes, such as increasing fluid intake and physical activity, can help prevent OIC 7
- Educational strategies can improve healthcare providers' knowledge on identifying and managing OIC 7
Pharmacological Therapies
- First-line management includes simple over-the-counter laxatives 7
- Alternative over-the-counter laxatives, secretogogues, or PAMORAs may be considered for patients refractory to initial measures 7
- Naloxegol, a PAMORA, has been shown to be effective and safe in treating OIC, with a limited side effect profile 3, 5, 6
Treatment Options
- Naloxegol is available through the oral route and is effective at a therapeutic dose of 25 mg daily 5
- Methylnaltrexone is another PAMORA option for treating OIC 5
- The bowel function index can be useful in objectively identifying patients who are refractory to initial measures 7