What is the treatment for opioid-induced constipation?

From the Guidelines

To treat opioid-induced constipation, start with preventive measures like increasing fluid intake to 2-3 liters daily, adding fiber to your diet, and maintaining physical activity as tolerated, and use a stimulant laxative such as senna or bisacodyl, often combined with a stool softener like docusate sodium, as recommended by the American Gastroenterological Association 1. For medication management, the following options can be considered:

• Stimulant laxatives: senna (8.6-17.2 mg daily) or bisacodyl (5-10 mg daily)
• Osmotic laxatives: polyethylene glycol (17 grams in 8 ounces of water daily) or lactulose (15-30 ml daily)
• Peripherally acting mu opioid receptor antagonists (PAMORAs): methylnaltrexone (subcutaneous injection, 8-12 mg every other day), naloxegol (12.5-25 mg daily), or lubiprostone (24 mcg twice daily) for severe cases that don't respond to first-line treatments, as supported by recent studies 1. It's essential to maintain a regular bowel routine and take these medications consistently while on opioid therapy, as constipation rarely improves on its own while continuing opioids. Key considerations for treatment include:
• Assessing the cause and severity of constipation to rule out obstruction or other underlying conditions 1
• Titration of laxatives as needed to achieve one non-forced bowel movement every 1-2 days 1
• Potential addition of other agents, such as magnesium hydroxide, bisacodyl, or lactulose, for persistent constipation 1
• Consideration of prokinetic agents, such as metoclopramide, for managing persistent constipation 1
• Evaluation of the need for prescription medications specifically for opioid-induced constipation, such as methylnaltrexone, naloxegol, or lubiprostone, for severe cases that don't respond to first-line treatments 1. Contact a healthcare provider if you experience severe abdominal pain, haven't had a bowel movement in 3-4 days despite treatment, or notice blood in your stool.

From the FDA Drug Label

MOVANTIK is an opioid antagonist 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. Recommended dosage: 25 mg once daily; if not tolerated, reduce to 12.5 mg once daily.

The treatment for opioid constipation is naloxegol (PO), with a recommended dosage of 25 mg once daily. If not tolerated, the dosage can be reduced to 12.5 mg once daily. Key considerations include:

• Discontinuing maintenance laxative therapy before starting naloxegol
• Taking naloxegol on an empty stomach at least 1 hour prior to the first meal of the day or 2 hours after the meal
• Avoiding consumption of grapefruit or grapefruit juice
• Discontinuing naloxegol if treatment with the opioid pain medication is also discontinued 2

From the Research

Treatment Options for Opioid Constipation

• Over-the-counter laxatives, such as osmotic laxatives (e.g., polyethylene glycol) or stimulant laxatives (e.g., anthraquinones), are recommended as first-line agents for opioid-induced constipation (OIC) and opioid-exacerbated constipation (OEC) due to their efficacy, low cost, and high safety profiles 3.
• Peripherally acting μ-opioid receptor antagonists (PAMORAs), such as methylnaltrexone, naloxegol, or naldemedine, can be used as second-line treatment for OIC that has not responded to combination laxative treatment 3, 4, 5.
• Naloxegol, a PAMORA, has been approved for the treatment of OIC in non-cancer patients and has shown efficacy in inhibiting OIC while preserving central analgesic actions 6, 7.

Management Strategies

• A comprehensive prevention and management strategy for OIC should include interventions that aim to improve fibre and fluid intake, increase mobility or exercise, and restore bowel function without compromising pain control 4.
• Fixed-dose combinations of opioids with μ opioid receptor antagonists, such as oxycodone/naloxone, have limited utility in clinical practice due to the inability to independently titrate the individual components 4.
• Prokinetics or intestinal secretagogues, such as lubiprostone, may be considered in the third-line setting, but their use in OIC is off-label in some countries and should be restricted to specialist centres and clinical trials 4.

Efficacy and Safety of PAMORAs

• PAMORAs have been shown to be effective in alleviating constipation without diminishing the analgesic effect of opioid therapy 5.
• Clinical studies have demonstrated the safety and efficacy of PAMORAs, such as methylnaltrexone, naldemedine, and naloxegol, for treating OIC 5.
• The use of PAMORAs has been updated to reflect their efficacy and safety in the management of OIC 5.