LUBIPROSTONE: A TARGETED APPROACH TO TREAT CHRONIC CONSTIPATION

Constipation is a very common problem and has a significant impact on the quality of life. Usually, people start with lifestyle modifications such as increasing fluid intake, eating fiber-rich foods, exercising regularly, and using over-the-counter (OTC) options like psyllium husk to improve symptoms. However, when these measures fail, and constipation becomes chronic or persistent, prescription medicines may be necessary.

Among prescription drugs, lubiprostone is a newer and scientifically validated option. It was approved by the U.S. Food and Drug Administration (FDA) in 2006, by the United Kingdom in 2014, and by Canada in 2015. Later, in 2008, it was approved for irritable bowel syndrome with constipation (IBS-C) and in 2013 for opioid-induced constipation (OIC) in adults with chronic non-cancer pain. It is approved for both men and women aged 18 years or above.

WHAT IS LUBIPROSTONE?

Lubiprostone is an oral laxative that works as a selective chloride channel activator (ClC-2). Chemically, it is difluoropentyl-2-hydroxy-6-oxo-octahydrocyclopentaheptanoic acid, a bicyclic fatty acid derivative of prostaglandin E1. Unlike older laxatives, it acts locally on the intestinal wall and does not significantly affect prostaglandin receptors or gastrointestinal smooth muscle.

Because of this local mechanism, lubiprostone produces a relatively quick onset of action and minimal systemic effects.

INDICATIONS

Lubiprostone is available by prescription only and is indicated for the following conditions:

1. Opioid-Induced Constipation (OIC):

Opioid analgesics are widely used to treat chronic pain, but they often cause constipation by binding to opioid receptors in the gut, reducing intestinal fluid secretion and motility.

Lubiprostone helps counteract this by restoring chloride and water flow into the intestines, improving stool passage.
Clinical studies have confirmed its benefit patients taking 24 µg twice daily showed significant increases in spontaneous bowel movements compared with placebo. (Cryer B. et al., 2014, Am J Gastroenterol)

2. Irritable Bowel Syndrome with Constipation (IBS-C):

IBS is a chronic disorder marked by abdominal pain, bloating, and altered bowel habits. In IBS-C, constipation predominates.

Lubiprostone at 8 µg twice daily has demonstrated meaningful relief of global IBS-C symptoms, including abdominal discomfort and stool consistency, in phase-3 clinical trials. (Drossman DA et al., 2009, Aliment Pharmacol Ther)

3. Chronic Idiopathic Constipation (CIC):

This refers to constipation that has no identifiable medical cause and persists for at least three months.

Several large placebo-controlled trials have shown lubiprostone to improve stool frequency, reduce straining, and enhance overall patient satisfaction. (Johanson JF et al., 2008, Dig Dis Sci)

DOSAGE FORM AND STRENGTH

Lubiprostone is available as liquid-filled gelatin capsules in two strengths:

• 24 mcg used for OIC and chronic idiopathic constipation

• 8 mcg used for IBS-C

It should always be taken with food and water to reduce nausea and improve absorption.

MECHANISM OF ACTION

To understand how lubiprostone works, it helps to know that the body has around nine types of chloride channels in various cells. These channels regulate the movement of chloride ions, which in turn control water flow and maintain cell volume and pH balance.

Lubiprostone selectively activates ClC-2 chloride channels located in the stomach, small intestine, and colon. Once activated, these channels allow the efflux of chloride ions into the intestinal lumen. Water follows this ion movement, increasing intestinal fluid secretion.

As a result, stools become softer, intestinal motility improves, and bowel movements often occur within 24 hours of starting therapy. Many patients also report less bloating and discomfort within a week.

Before the development of lubiprostone, patients with severe laxative-resistant constipation were often treated with methylnaltrexone bromide, an opioid receptor antagonist that required subcutaneous injection. Lubiprostone, therefore, offers a non-invasive oral alternative with proven efficacy.

DOSING GUIDELINES

OIC and Chronic Idiopathic Constipation:
24 mcg twice daily with food and water

IBS-C: 8 mcg twice daily with food and water

In patients with hepatic impairment, the dose should be reduced. Dose adjustments may also be necessary if adverse effects occur.

PHARMACOKINETICS

Lubiprostone is metabolized locally in the stomach and jejunum by carbonyl reductase via oxidation/reduction reactions. It does not rely on the liver’s cytochrome P450 system, which means fewer drug interactions.

Its active metabolite (M3) represents around 10% of the administered dose and is 94% protein-bound, with a half-life of about one hour.

Around 60% is excreted in urine and 30% in feces, indicating efficient elimination.

PRECAUTIONS

To ensure safe and effective use, follow these precautions:

• Take lubiprostone at the same time every day and never exceed the prescribed dose.

• Inform your doctor about any diarrhea, intestinal obstruction, or liver disease, as well as all other medications or herbal supplements you are taking.

• Transient dyspnea (shortness of breath) or chest tightness may occur within one hour after the first dose, usually resolving within three hours.

• Hypotension and syncope (fainting) may occur within the first hour after taking the medication.

• If nausea or diarrhea occurs, stay hydrated to prevent low blood pressure.
(FDA Prescribing Information, 2023)

CONTRAINDICATIONS

• Known allergy to lubiprostone

• Suspected or known gastrointestinal obstruction

• Diarrhea-predominant IBS

• Concurrent use with methadone, which can reduce chloride channel activation

ADVERSE EFFECTS

• Common side effects include:

• Nausea, vomiting, headache, dizziness

• Abdominal pain, diarrhea, or bloating

• Dyspnea or chest discomfort (transient)

• Hypotension or tachycardia

• Muscle cramps and dry mouth

• Peripheral swelling, rash, or fatigue

If any severe reactions such as difficulty breathing, facial swelling, or persistent diarrhea occur, seek immediate medical help.

Safety in children, pregnant, and breastfeeding women has not been fully established. Although animal studies show no drug excretion in milk, human data are lacking.

FAQs

1. How fast does lubiprostone work?
Most patients experience a bowel movement within 24 hours, though some may need a few days for full relief.

2. Can lubiprostone be used with other laxatives?
It can be used with dietary fiber or stool softeners, but avoid other prescription laxatives unless advised by your doctor.

3. Is lubiprostone habit-forming?
No, it does not act on opioid or stimulant pathways, so it is not habit-forming.

4. Can pregnant women take lubiprostone?
Data are limited. It should be used only if clearly needed and prescribed by a physician after risk-benefit evaluation.

5. What should I do if I miss a dose?
Take it as soon as you remember, unless it’s almost time for the next dose. Do not double the dose.

DISCLAIMER

This article is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult your physician or pharmacist before starting or changing any medication. Individual responses and side effects may vary.

CALL TO ACTION

If you or someone you know suffers from chronic constipation that hasn’t improved with home remedies, speak with your healthcare provider about whether lubiprostone could be a safe and effective option.

For more health education content on gastrointestinal disorders and drug therapy, follow PharmaHealths for evidence-based updates.

REFERENCES

1. Johanson JF, Morton D, Geenen J, et al. “Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of lubiprostone, a locally acting type-2 chloride channel activator, in chronic constipation.” Am J Gastroenterol. 2008;103(1):170–177.

2. Drossman DA, Chey WD, Johanson JF, et al. “Lubiprostone reduces symptoms of irritable bowel syndrome with constipation: Results from two randomized, double-blind, placebo-controlled studies.” Aliment Pharmacol Ther. 2009;29(3):329–341.

3. Cryer B, Drossman DA, Chey WD, et al. “Efficacy and safety of lubiprostone in patients with opioid-induced constipation.” Am J Gastroenterol. 2014;109(7):1139–1145.

4. Wilson N, et al. “Lubiprostone in constipation: clinical evidence and place in therapy.” Ther Adv Chronic Dis. 2019;10:2040622319862691.

5. FDA. Amitiza (lubiprostone) Prescribing Information, Revised 2023. 6. Mayo Clinic. “Lubiprostone oral route: description and precautions.” Updated 2025.