What does Amitiza (lubiprostone) do?

What Does Amitiza (Lubiprostone) Do?

Amitiza (lubiprostone) is a chloride channel activator that enhances intestinal fluid secretion, increases motility in the intestine, and facilitates stool passage to treat constipation-related conditions. 1

Mechanism of Action

Lubiprostone works through a specific mechanism:

• Activates ClC-2 chloride channels in the apical membrane of intestinal epithelial cells 1
• Enhances chloride-rich intestinal fluid secretion without altering serum sodium and potassium levels 1
• Increases intestinal motility by increasing fluid in the bowel lumen 1
• Acts locally within the gastrointestinal tract with minimal systemic absorption 1, 2

FDA-Approved Indications

Lubiprostone is approved for three main conditions:

1. Chronic Idiopathic Constipation (CIC) - 24 mcg twice daily 1

2. Opioid-Induced Constipation (OIC) - 24 mcg twice daily 1

   • For adult patients with chronic non-cancer pain
   • Not established for patients taking diphenylheptane opioids (e.g., methadone)

3. Irritable Bowel Syndrome with Constipation (IBS-C) - 8 mcg twice daily 1

   • Approved specifically for women ≥18 years old

Clinical Efficacy

Lubiprostone has demonstrated effectiveness in multiple clinical scenarios:

• For Chronic Idiopathic Constipation: Improves stool frequency, consistency, and reduces straining 3
• For IBS-C: Improves global symptoms, abdominal pain, and bowel movements 3
• For Opioid-Induced Constipation: Effective for treating OIC in patients with chronic non-cancer pain 3

The American Gastroenterological Association (AGA) suggests using lubiprostone in patients with IBS-C (conditional recommendation, moderate certainty) 3. Similarly, the British Society of Gastroenterology recommends lubiprostone as an efficacious second-line drug for IBS-C in secondary care 3.

Common Side Effects

The most common adverse reactions include:

• Nausea (most common, occurring in up to 35% of patients) 3, 1
• Diarrhea 1
• Headache 1
• Abdominal pain and distension 1
• Flatulence 1

Important Considerations and Cautions

• Contraindicated in patients with known or suspected mechanical gastrointestinal obstruction 1
• Should be taken with food and water to reduce nausea 3, 1
• Dosage adjustment needed for patients with moderate to severe hepatic impairment 1
• Not recommended for patients with severe diarrhea 1
• May cause syncope and hypotension, particularly after the first dose 1
• Dyspnea may occur within an hour of the first dose 1

Clinical Pearls

• Nausea is dose-dependent and typically mild to moderate; taking with food can reduce this side effect 3
• Effects generally manifest within 2 days in responsive patients 3
• Efficacy in persons 65 years and older is comparable to the overall population 3
• Systemic absorption is negligible, making it a good option for patients with multiple medications 1, 2
• Can be used in combination with peripherally acting μ-opioid receptor antagonists like methylnaltrexone for enhanced effect in opioid-induced constipation 3

Lubiprostone offers a novel approach to treating constipation by addressing the underlying fluid secretion issues rather than simply stimulating motility like traditional laxatives 4.