Using the chloride channel activator Lubiprostone to treat IBS-C . symptoms

This is an automatically translated article.

The article was written by Master - Doctor Mai Vien Phuong - Head of Gastrointestinal Endoscopy Unit - Department of Medical Examination and Internal Medicine - Vinmec Central Park International General Hospital.
Chronic idiopathic constipation (CC) and irritable bowel syndrome (IBS) with constipation-predominant (IBS-C) are common conditions in North America and often difficult to treat effectively. The prevalence of IBS is about 11%, of which, IBS-C accounts for 22% to 35%. Lubiprostone is one of two chloride channel activators approved for the treatment of IBS-C.

1. What is Lubiprostone?

Lubiprostone is a locally acting prostaglandin E1 analog with high affinity for type 2 chloride channels located in the apical membrane of intestinal epithelial cells. Activation of these receptors increases bowel secretion and motility. Animal studies have suggested that lubiprostone may restore barrier function in individuals with increased intestinal permeability. Lubiprostone is approved by the US FDA for the treatment of IBS-C in adult women at a dose of 8 μg twice daily.

2. Evidence from studies

Lubiprostone has been evaluated in 3 randomized controlled trials and one high-quality systematic review/meta-analysis. Later, lubiprostone was found to be more effective than placebo for overall IBS-C symptoms. The most robust data included in that analysis came from 2 identically designed phase III studies including 1,171 patients who met the Rome II criteria for IBS-C, who were randomized to receive 8 μg lubiprostone or placebo twice daily with meals for 12 weeks.
Efficacy was observed in 17.9% of lubiprostone users compared with 10.1% of placebo users. Differences between groups did not reach statistical significance until month 2 but were maintained throughout March. Secondary analyzes in these phase III studies also identified significant improvements in abdominal pain/discomfort, bloating, strain, frequency and consistency of stools.

3. Safety and tolerability

Regarding safety and tolerability, diarrhea (6%–14%) and nausea (8%–19%) were the most frequently reported events (mean 11% for both effects). extra). In a recent analysis of nausea across all IBS-C studies, the overall incidence of treatment-emergent nausea in the randomized controlled trial was significantly higher in patients receiving lubiprostone compared with patients receiving lubiprostone. placebo (10.9% vs 6.4%, respectively). Discontinuation rates were generally low (1.2%) and comparable to placebo (0.7%). The feeling of nausea can be minimized by concurrent consumption of food.
Chey et al determined the long-term safety, tolerability, and occurrence of adverse events in 522 subjects, mainly women (93%) with IBS-C who received lubiprostone 8 μg, twice daily for 36 weeks. No serious drug-related side effects were observed. During the study period, no significant changes were noted. 21 of 522 subjects (4%) discontinued lubiprostone due to adverse events. 41 subjects (7.9%) had their dose reduced due to adverse events, 4 of which eventually discontinued simultaneously. The overall rate of treatment-related adverse events was 25.4%. Diarrhea (11.0%), nausea (11.0%) and abdominal distention (5.8%) were the most common adverse events associated with lubiprostone.
Of the subjects diarrhea, most were mild to moderate and resulted in 6 (1.2%) subjects discontinuing the drug. Similarly, 3 (0.6%) subjects discontinued lubiprostone due to nausea. Based on these results, the authors concluded that, for subjects with IBS-C, lubiprostone 8 μg twice daily was safe and well-tolerated for 13 months of use.
Dyspnea has been reported in a few studies, with a prevalence of 0.4%. Although rare, this side effect usually occurs within an hour of the first dose, lasts no more than a few hours, and often recurs with continued use. However, shortness of breath usually resolves on its own and is not considered a serious side effect.

4. Conclusion

Lubiprostone at a dose of 8 μg BID is currently FDA-approved to treat women 18 years of age and older with IBS-C. Several studies have confirmed its effectiveness, and its continued use is associated with improvement in symptoms. The majority of subjects in all studies were female. Based on long-term studies, lubiprostone is safe and generally well tolerated and has not been associated with any life-threatening events. Pregnant women or those planning to become pregnant should not take lubiprostone. Safety has been evaluated for up to 13 months and currently, there is no limit to the duration of treatment, however, indications should be regularly reevaluated. The most common side effects were nausea, diarrhea, bloating, and dizziness. In conclusion, Lubiprostone is currently an excellent treatment option for IBS-C.
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References: journals.lww.com