Usage
Lubiprostone is prescribed for the treatment of chronic idiopathic constipation (CIC) in adults, opioid-induced constipation (OIC) in adults with chronic non-cancer pain (including patients with chronic pain related to prior cancer or its treatment who do not require frequent opioid dosage escalation), and irritable bowel syndrome with constipation (IBS-C) in women aged 18 years and older. It’s classified as a chloride channel activator, specifically a CIC-2 activator. Lubiprostone acts locally in the gut, increasing intestinal fluid secretion and promoting intestinal motility.
Alternate Names
The international brand name for lubiprostone is Amitiza. Other brand names include Lubowel and Lubilax.
How It Works
Pharmacodynamics: Lubiprostone activates chloride channels (CIC-2) on the apical membrane of intestinal epithelial cells. This activation increases chloride secretion into the intestinal lumen, leading to increased fluid secretion and enhanced motility. This softens the stool and facilitates bowel movements.
Pharmacokinetics: Lubiprostone has low systemic absorption. It is metabolized primarily in the stomach and jejunum by carbonyl reductase. Its metabolite, M3, is formed in the gut. This metabolite does undergo absorption and has higher bioavailability compared to lubiprostone itself. Lubiprostone’s elimination half-life is relatively short (0.9-1.4 hours). About 60% of the administered dose is excreted in the urine, and trace amounts are found in feces.
Dosage
Standard Dosage
Adults:
- CIC and OIC: 24 mcg twice daily, orally with food and water.
- IBS-C: 8 mcg twice daily, orally with food and water.
Children:
Lubiprostone use is not established in children.
Special Cases:
- Elderly Patients: No specific dosage adjustments are typically required based on age alone. However, close monitoring is always advisable.
- Patients with Renal Impairment: No dosage adjustments are needed.
- Patients with Hepatic Dysfunction: Dosage adjustments are necessary:
- Moderate (Child-Pugh B): 16 mcg twice daily. If this dose is tolerated and an adequate response is not achieved, it can be increased to the full dose (24 mcg twice daily) with careful monitoring.
- Severe (Child-Pugh C): 8 mcg twice daily. Escalation to the full dose may be considered if tolerated and necessary.
- Patients with Comorbid Conditions: Use with caution in patients with severe diarrhea. No specific dosage adjustments are typically needed for patients with diabetes or cardiovascular disease.
Clinical Use Cases
Lubiprostone is not indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its use is specifically for chronic constipation disorders as outlined above.
Dosage Adjustments
If significant nausea occurs, consider reducing the dosage, but maintain twice-daily administration with food. Always carefully monitor patient response and tolerance.
Side Effects
Common Side Effects:
Nausea (most common), diarrhea, headache, abdominal pain, abdominal distension, flatulence, vomiting.
Rare but Serious Side Effects:
Syncope, hypotension, ischemic colitis, hypersensitivity reactions (rash, swelling, throat tightness, malaise), dyspnea.
Long-Term Effects:
Chronic complications from prolonged lubiprostone use are generally uncommon. However, patients should be periodically reassessed for the continued need for therapy.
Adverse Drug Reactions (ADR):
Significant ADRs include syncope/hypotension, dyspnea, severe diarrhea, and hypersensitivity reactions. These require immediate medical attention and discontinuation of the drug.
Contraindications
Lubiprostone is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction, as well as those with severe diarrhea.
Drug Interactions
Limited information is available on drug interactions with lubiprostone, likely due to its minimal systemic absorption. However, concomitant administration with other medications that cause diarrhea might exacerbate gastrointestinal side effects. Always consider patient-specific factors and monitor for any potential adverse effects.
Pregnancy and Breastfeeding
Lubiprostone is categorized as Pregnancy Category C. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Data on lubiprostone excretion into breast milk and its effects on nursing infants are limited. Therefore, caution is advised during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Chloride channel (CIC-2) activator, increases intestinal fluid secretion and motility.
- Side Effects: Nausea, diarrhea, headache, abdominal pain, syncope, dyspnea.
- Contraindications: Mechanical gastrointestinal obstruction, severe diarrhea.
- Drug Interactions: Limited data available.
- Pregnancy & Breastfeeding: Use with caution; assess risk/benefit.
- Dosage: CIC/OIC: 24 mcg BID; IBS-C (women): 8 mcg BID. Adjust for hepatic impairment.
- Monitoring Parameters: Bowel movement frequency, severity of side effects (nausea, diarrhea), fluid and electrolyte balance.
Popular Combinations
Lubiprostone is typically not used in combination with other drugs for its indicated conditions.
Precautions
- General Precautions: Screen patients for potential gastrointestinal obstruction and monitor for the development of severe diarrhea.
- Specific Populations: Use with caution in pregnancy and breastfeeding. No established use in children.
- Lifestyle Considerations: Lubiprostone may cause dizziness; advise patients against driving or operating machinery until they know how the medication affects them.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Lubiprostone?
A: For CIC and OIC, it’s 24 mcg twice daily. For IBS-C in women, it’s 8 mcg twice daily.
Q2: What is the mechanism of action of Lubiprostone?
A: Lubiprostone activates chloride channels (CIC-2) in the gut, increasing fluid secretion and intestinal motility.
Q3: What are the common side effects of Lubiprostone?
A: Nausea, diarrhea, headache, and abdominal discomfort are the most frequently reported side effects.
Q4: Is Lubiprostone safe to use during pregnancy?
A: Lubiprostone is a Pregnancy Category C drug. Use only if the potential benefit outweighs the potential risk to the fetus.
Q5: What are the contraindications for Lubiprostone?
A: Known or suspected mechanical gastrointestinal obstruction and severe diarrhea are absolute contraindications.
Q6: How should Lubiprostone be administered?
A: Orally, with food and water, twice daily. Capsules should be swallowed whole and not crushed or chewed.
Q7: Does Lubiprostone interact with other medications?
A: Due to its low systemic absorption, significant drug interactions are not commonly observed. However, concomitant use with other drugs that cause diarrhea may worsen gastrointestinal side effects.
Q8: How long does it take for Lubiprostone to work?
A: Patients may experience an increase in bowel movements within 24 to 48 hours of starting the medication.
Q9: What should I do if a patient experiences severe diarrhea while taking Lubiprostone?
A: Discontinue the medication immediately and contact the patient’s healthcare provider.
Q10: Can Lubiprostone be used in men with IBS-C?
A: Lubiprostone is not currently approved for use in men with IBS-C. Studies have not adequately demonstrated its efficacy and safety in this population.
