From the Guidelines
For the treatment of opioid-induced constipation, I strongly recommend starting with a peripherally acting mu opioid receptor antagonist (PAMORA) such as naloxegol (12.5-25 mg once daily) or methylnaltrexone (450 mg orally once daily), as they have been shown to be effective in managing OIC with a strong recommendation and moderate quality evidence 1, 2.
Treatment Approach
When managing opioid-induced constipation, it's essential to consider the underlying mechanism of opioid-induced constipation, which involves the binding of opioids to mu-receptors in the intestines, leading to slowed gut motility and reduced secretions. The American Gastroenterological Association (AGA) recommends the use of laxatives as first-line agents, including osmotic laxatives like polyethylene glycol (17-34 g/day) and stimulant laxatives like senna (8.6-17.2 mg daily) or bisacodyl (5-10 mg daily) 2.
Key Considerations
- Opioid-induced constipation affects up to 80% of patients taking chronic opioid therapy, making preventive treatment essential throughout opioid therapy 2.
- The Rome IV criteria for OIC include new or worsening symptoms of constipation when initiating, changing, or increasing opioid therapy, with at least two of the following symptoms present more than 25% of the time: straining, lumpy/hard stools, sensation of incomplete evacuation, sensation of anorectal obstruction/blockage, manual maneuvers to facilitate defecation, or reduced stool frequency (fewer than 3 spontaneous bowel movements per week) 2.
- Increasing fluid intake to at least 8 glasses of water daily and incorporating physical activity, if possible, can also help manage OIC.
Medication Options
- Naloxegol (12.5-25 mg once daily) and methylnaltrexone (450 mg orally once daily) are prescription medications specifically designed for opioid-induced constipation and have been shown to be effective in managing OIC 1, 2.
- Lubiprostone (24 mcg twice daily) is another option for managing OIC, although it may not be as effective as PAMORAs in some cases.
Conclusion is not allowed, so the answer just ends here with the last point.
From the FDA Drug Label
MOVANTIK ®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. RELISTOR is a prescription medicine used to treat constipation in adults that is caused by prescription pain medicines called opioids: RELISTOR tablets and RELISTOR injection are used to treat constipation caused by opioids in adults with long-lasting (chronic) pain that is not caused by active cancer RELISTOR injection is used to treat constipation caused by opioids in adults with advanced illness or pain caused by active cancer and who need increases in their opioid dose for comfort care.
The medications used to treat opioid-induced constipation are:
- Naloxegol (PO), as indicated in the MOVANTIK label 3
- Methylnaltrexone (SQ), as indicated in the RELISTOR label 4
From the Research
Medications for Opioid-Induced Constipation
The following medications are used to treat opioid-induced constipation:
- Peripherally acting μ-opioid receptor antagonists (PAMORAs) such as methyltrexone, naldemedine, and naloxegol 5, 6, 7
- Methylnaltrexone, which can be administered orally or parentally 6, 8
- Naloxegol, which is an oral medication 7, 9
- Naldemedine, which is an oral medication 6, 8, 9
- Lubiprostone, which is a prescription-strength laxative 9
- Prucalopride, which is a prescription-strength laxative 9
Mechanism of Action
PAMORAs work by antagonizing the effects of opioids on the gastrointestinal system, without affecting the analgesic benefits of opioid pain relievers 5, 6. They have a limited ability to cross the blood-brain barrier, allowing them to target peripheral μ-opioid receptors in the enteric system 5, 6.
Efficacy and Safety
Clinical studies have demonstrated the safety and efficacy of PAMORAs in alleviating constipation without diminishing the analgesic effect of opioid therapy 5, 6, 9. A systematic review and meta-analysis found that μ-opioid-receptor antagonists, including PAMORAs, were superior to placebo for the treatment of opioid-induced constipation, with a relative risk of failure to respond to therapy of 0.70 (95% CI, 0.64-0.75) 9. However, patients who received μ-opioid-receptor antagonists were significantly more likely to have diarrhea, abdominal pain, nausea, or vomiting than patients who received placebo 9.