Safety and Efficacy of Amitiza (Lubiprostone) for Chronic Constipation
Amitiza (lubiprostone) is a safe and effective FDA-approved medication for the treatment of chronic idiopathic constipation in adults, with demonstrated efficacy in improving bowel movements and associated symptoms. 1
Mechanism of Action and Indications
- Lubiprostone is an orally active prostaglandin analog that activates select chloride channels in the intestinal epithelium, enhancing intestinal fluid secretion and promoting bowel movements without directly stimulating gastrointestinal smooth muscle 2
- FDA-approved for three specific indications:
- Chronic idiopathic constipation (CIC) in adults at 24 mcg twice daily
- Opioid-induced constipation (OIC) in adults with chronic non-cancer pain at 24 mcg twice daily
- Irritable bowel syndrome with constipation (IBS-C) in women ≥18 years at 8 mcg twice daily 1
Efficacy for Chronic Constipation
- Multiple randomized controlled trials have demonstrated that lubiprostone significantly improves:
- The American Gastroenterological Association-American College of Gastroenterology clinical practice guideline suggests lubiprostone for adults with chronic idiopathic constipation who do not respond to over-the-counter agents (conditional recommendation, low certainty of evidence) 2
- Lubiprostone can be used either as a replacement for or as an adjunct to over-the-counter laxatives when those agents fail to provide adequate relief 2
Dosing Considerations
- Standard dosing for chronic constipation: 24 mcg twice daily with food and water 2, 1
- Dose adjustments required for hepatic impairment:
- Moderate impairment (Child-Pugh Class B): 16 mcg twice daily
- Severe impairment (Child-Pugh Class C): 8 mcg twice daily 1
- Capsules should be swallowed whole and not broken apart or chewed 1
- Taking with food can reduce the incidence of nausea 1, 5
Safety Profile
- Most common adverse effects:
- Risk of nausea is dose-dependent and appears to be lower when taken with food and water 2, 4
- Contraindicated in patients with known or suspected mechanical gastrointestinal obstruction 1
- Patients should be instructed to discontinue lubiprostone and contact their healthcare provider if severe diarrhea occurs 1
- Long-term studies have demonstrated an acceptable safety profile 5, 6
Place in Therapy
- Lubiprostone should be considered after failure of first-line treatments for chronic constipation, which include:
- Lifestyle modifications (increased fluid intake and physical activity)
- Dietary fiber (for patients with adequate fluid intake)
- Over-the-counter laxatives (osmotic agents like polyethylene glycol, stimulant laxatives) 2
- The NCCN Palliative Care guidelines recognize lubiprostone as an effective option for treating constipation, particularly for opioid-induced constipation in patients with chronic non-cancer pain 2
- The American Gastroenterological Association includes lubiprostone as a recommended option for treating constipation associated with irritable bowel syndrome 2
Cost Considerations
- Monthly cost of lubiprostone is approximately $374, which is higher than most over-the-counter options but comparable to other prescription medications for chronic constipation 2
- This cost factor may influence treatment decisions, particularly when considering long-term therapy 2
Clinical Pearls and Caveats
- Duration of treatment in clinical trials was typically 4 weeks, but the drug label does not provide a specific limit for treatment duration 2
- Lubiprostone could be used in combination with a peripherally acting μ-opioid receptor antagonist such as methylnaltrexone for patients with opioid-induced constipation 2
- Physicians should periodically assess the need for continued therapy 1
- Lubiprostone offers a novel mechanism of action compared to traditional laxatives, making it a valuable option for patients who have become refractory to other treatments 7, 5