From the Guidelines
Medication options for opioid-induced constipation should start with over-the-counter treatments such as stool softeners, stimulant laxatives, and osmotic agents, with prescription medications like peripherally acting mu-opioid receptor antagonists (PAMORAs) considered if these are ineffective. The American Gastroenterological Association (AGA) recommends the use of laxatives as first-line agents for opioid-induced constipation (OIC) 1. First-line treatments typically include:
- Stool softeners like docusate sodium (100-300 mg daily)
- Stimulant laxatives such as senna (8.6-17.2 mg daily) or bisacodyl (5-15 mg daily)
- Osmotic agents like polyethylene glycol (17 g in 8 oz water daily)
If these are ineffective, prescription medications specifically targeting opioid-induced constipation may be necessary, including:
- Peripherally acting mu-opioid receptor antagonists (PAMORAs) such as naloxegol (12.5-25 mg daily) 1, methylnaltrexone (subcutaneous injection, 8-12 mg every other day), or naldemedine (0.2 mg daily)
- Lubiprostone (24 mcg twice daily) is another prescription option that increases intestinal fluid secretion
A stepwise approach is recommended, starting with over-the-counter options and adding prescription medications if needed. These medications work by either softening stool, increasing bowel motility, or specifically blocking opioid effects on intestinal receptors without interfering with pain control. Adequate hydration and dietary fiber should accompany medication treatment. Patients should start treatment when beginning opioid therapy rather than waiting for constipation to develop, as prevention is easier than treatment of established constipation 1. The AGA also suggests naldemedine over no treatment for patients with laxative refractory OIC, with a strong recommendation and high-quality evidence 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.
The medication options for opioid-induced constipation include:
- Lubiprostone (PO): indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain 2
- Naloxegol (PO): used for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain 3 3 Key considerations:
- Lubiprostone is not effective in patients taking diphenylheptane opioids (e.g., methadone) 2
- Naloxegol is contraindicated in patients with known or suspected gastrointestinal obstruction or in patients at risk of recurrent obstruction 3 3
From the Research
Medication Options for Opioid-Induced Constipation
Medication options for opioid-induced constipation (OIC) include several classes of drugs that aim to alleviate constipation without compromising pain management. The following are some of the key medication options:
- Naloxegol: An oral, peripherally acting μ-opioid receptor antagonist, shown to be effective in treating OIC in patients with noncancer pain 4, 5. Naloxegol has been demonstrated to increase the frequency of spontaneous bowel movements and improve symptoms of constipation without affecting opioid-mediated analgesia.
- Methylnaltrexone: A quaternary amine mu-opioid receptor antagonist that has restricted ability to cross the blood-brain barrier, making it a suitable option for treating OIC without compromising central analgesia 6, 7. Methylnaltrexone has been shown to rapidly induce laxation in patients with advanced illness and OIC.
- Lubiprostone: A locally acting chloride channel activator that can increase intestinal fluid secretion, which may help alleviate constipation symptoms 8.
- Linaclotide: A guanylate cyclase-C agonist that increases intestinal fluid secretion and transit, which can help treat constipation 8.
- Naldemedine: A peripherally acting μ-opioid receptor antagonist specifically designed for the treatment of OIC, which has shown efficacy in clinical trials 8.
- Oxycodone/naloxone combinations: These combinations aim to provide pain relief while also addressing constipation symptoms by including an opioid receptor antagonist 8.
Key Considerations
When selecting a medication for OIC, it is essential to consider the individual patient's needs, the type of opioid being used, and potential side effects. For example:
- The efficacy of methylnaltrexone may vary depending on the opioid subtype being used 7.
- Naloxegol has been associated with gastrointestinal side effects, such as abdominal pain and diarrhea 4, 5.
- The choice of medication should be guided by the patient's medical history, current medications, and the severity of their constipation symptoms.
Emerging Therapies
Research continues to explore new and innovative treatments for OIC, including the development of novel peripherally acting μ-opioid receptor antagonists and other classes of drugs that target different pathways involved in constipation 8. These emerging therapies may offer additional options for managing OIC in the future.