What is Amitiza (lubiprostone)?

Amitiza (Lubiprostone): A Chloride Channel Activator for Constipation

Amitiza (lubiprostone) is a chloride channel activator medication FDA-approved for treating chronic idiopathic constipation, opioid-induced constipation, and irritable bowel syndrome with constipation (IBS-C) in women. 1

Mechanism of Action

• Lubiprostone works by specifically activating ClC-2 chloride channels in the apical membrane of intestinal epithelial cells, enhancing chloride-rich intestinal fluid secretion 1
• This increased fluid secretion promotes intestinal motility, facilitating stool passage and alleviating constipation symptoms 1
• The medication acts locally within the gastrointestinal tract with minimal systemic absorption 1
• By increasing intestinal fluid, lubiprostone bypasses the antisecretory action of opiates, making it effective for opioid-induced constipation 1

FDA-Approved Indications

• Chronic idiopathic constipation (CIC) in adults - 24 mcg twice daily 1
• Opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain - 24 mcg twice daily 1
• Irritable bowel syndrome with constipation (IBS-C) in women ≥18 years old - 8 mcg twice daily 1

Formulation and Administration

• Available as soft gelatin capsules in two strengths: 8 mcg (pink) and 24 mcg (orange) 1
• Should be taken with food and water to reduce the risk of nausea 2
• Capsules should be swallowed whole, not broken apart or chewed 1
• Effects typically manifest within 2 days in patients who respond to treatment 2

Efficacy

• Clinical trials demonstrated that lubiprostone significantly increases spontaneous bowel movements compared to placebo 3
• Improves stool consistency, reduces straining, and alleviates constipation severity 4
• Beneficial effects on abdominal discomfort and bloating, which are bothersome symptoms in some individuals with constipation 2
• No evidence of rebound constipation following cessation of treatment 4

Special Populations and Dosing Considerations

• Patients with moderate to severe hepatic impairment should receive a reduced dose of 8 mcg twice daily 2
• Efficacy in persons 65 years and older is comparable to the overall population 2
• Not recommended for patients with known or suspected mechanical gastrointestinal obstruction 1
• Safety and effectiveness have not been established in pediatric patients 1

Side Effects and Precautions

• Nausea is the most common adverse event (reported in up to 35% of individuals), but typically mild to moderate 3
• Only about 5% of patients discontinue therapy due to nausea 3
• Other common adverse reactions include diarrhea, headache, abdominal pain, abdominal distension, and flatulence 1
• Rare side effects include dyspnea (shortness of breath), which may occur within an hour of the first dose 1
• Syncope and hypotension may occur after taking the first dose or with subsequent doses 1

Clinical Position in Treatment Algorithms

• For chronic idiopathic constipation: Suggested for adults who do not respond to over-the-counter agents 3
• Can be used as a replacement for or as an adjunct to OTC agents 3
• For IBS-C: Considered an efficacious second-line drug in secondary care 3
• For opioid-induced constipation: Effective for relieving OIC while preserving opioid-mediated analgesia 3

Pharmacokinetics

• Following oral administration, concentrations of lubiprostone in plasma are below the level of quantitation (10 pg/mL) 1
• The medication is rapidly and extensively metabolized 1
• Approximately 94% bound to human plasma proteins 1
• Should be taken with food to reduce side effects, although a high-fat meal can decrease peak concentration by 55% 1