Analysis of the impact on efficacy of lubiprostone dose reduction to manage adverse events in the treatment of chronic constipation in Japan

ABSTRACT

Objective

To compare outcomes between two doses of lubiprostone in patients with chronic constipation (CC), to assess whether dose reduction affects efficacy.

Methods

This open-label exploratory study involved 146 patients with CC treated initially with lubiprostone 24 mcg twice daily for a planned duration of 4 weeks. Patients who experienced adverse events (AEs) had their dose reduced to 12 mcg twice daily (for 4 weeks).

Results

Lubiprostone dose was unchanged in 104 patients and reduced due to AEs in 42 patients. Significant differences in the mean number of bowel movements per week favored the dose-reduced group at Week 1 and end of follow-up. No between-group differences were observed over time for mean number of days per week with bowel movements or mean Bristol Stool Form Scale scores. Symptoms of abdominal bloating, strained defecation, and sensation of incomplete evacuation improved in both groups. Before dose reduction, nausea was reported by 64.3% and diarrhea by 45.2% of patients in the dose-reduced group; after dose reduction, no patients reported nausea and one patient reported diarrhea.

Conclusion

Dose reduction of lubiprostone reduced the incidence of AEs, with no compromise to efficacy, and may be a suitable approach for patients who develop AEs during treatment.

KEYWORDS:

• Lubiprostone
• chronic constipation
• adverse events
• dose reduction
• efficacy

Acknowledgments

The authors thank Turacoz Healthcare Solutions, Gurugram, India, for writing support. Editorial assistance was also provided by Content Ed Net.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Peer reviewer disclosures

A peer reviewer on this manuscript has disclosed grant support from Mylan EPD which is the supplier of lubiprostone in Japan, and also received lecture fees. Peer reviewers on this manuscript have no other conflicts of interest to declare.

Author contributions

H Ohbayashi designed the study.

H Ohbayashi, Y Sato, M Kiuchi, A Nagazumi and T Kimura acquired the data.

H Ohbayashi was involved in data analysis.

H Ohbayashi wrote the paper.

T Kanzo critically reviewed the manuscript.

All authors read and gave approval of the final version of the article to be published.

Additional information

Funding

This study was funded by Mylan EPD G.K. Editorial assistance was funded by Mylan EPD G.K.