Efficacy of Itopride in the Prevention of Lubiprostone-Induced Nausea

Tatsuya Abe, Yoshikazu Hachiro, Yoshiaki Ebisawa, Houhei Hishiyama, Masanori Murakami, Masao Kunimoto

Department of Gastroenterology, Kunimoto Hospital, Asahikawa, Japan.
Department of Proctology, Kunimoto Hospital, Asahikawa, Japan.

DOI: 10.4236/ojgas.2014.49044                

Abstract

Background: The efficacy of lubiprostone for chronic constipation has been established through phase III clinical trials. Nevertheless, the continuation of lubiprostone therapy is reportedly difficult due to the development of nausea. The objective of this study is to determine whether the administration of itopride hydrochloride can reduce lubiprostone-related nausea. Methods: Two hundred and thirty-five patients who were receiving lubiprostone (24 μg capsule twice daily) were enrolled. Seventy-one patients took a prophylactic dose of itopride (50 mg tablet twice daily) together with lubiprostone to prevent nausea. Thus, the patients were divided into 2 groups: lubiprostone alone (164; control group) and combination therapy with lubiprostone and itopride (71; itopride group). Efficacy measures included changes in constipation scoring system scores, the incidence of treatment-related adverse events including nausea, and the percentage of patients who discontinued treatment within two weeks after administration. Results: Of the 235 patients who were enrolled, 196 were available for analysis. Both treatment groups experienced statistically significant improvements in constipation scoring system scores. The percentage of patients who reported ≥1 adverse event was significantly higher in the control group (40.9%) than in the itopride group (21.9%). The percentage of patients experiencing nausea was statistically and significantly lower in the itopride group than in the control group (9.4% versus 22.7%). The itopride regimen was also statistically superior compared to the control regimen in terms of treatment discontinuation. Conclusion: The prophylactic administration of itopride can decrease the risk of nausea in patients receiving lubiprostone and consequently reduce the risk of treatment discontinuation.

Keywords

Chronic Constipation, Itopride, Lubiprostone, Nausea

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Lembo, A. and Camilleri, M. (2003) Chronic constipation. The New England Journal of Medicine, 349, 1360-1368. http://dx.doi.org/10.1056/nejmra020995
[2]	Johanson, J.F. and Kralstein, J. (2007) Chronic Constipation: A Survey of the Patient Perspective. Alimentary Pharmacology & Therapeutics, 25, 599-608. http://dx.doi.org/10.1111/j.1365-2036.2006.03238.x
[3]	Johanson, J.F. and Ueno, R. (2007) Lubiprostone, a Locally Acting Chloride Channel Activator, in Adult Patients with Chronic Constipation: A Double-Blind, Place-bo-Controlled, Dose-Ranging Study to Evaluate Efficacy and Safety. Alimentary Pharmacology & Therapeutics, 25, 1351-1361. http://dx.doi.org/10.1111/j.1365-2036.2007.03320.x
[4]	Johanson, J.F., Morton, D., Geenen, J. and Ueno, R. (2008) Multicenter, 4-Week, Double-Blind, Randomized, Placebo-Controlled Trial of Lubiprostone, a Locally-Acting Type-2 Chloride Channel Activator, in Patients with Chronic Constipation. The American Journal of Gastroenterology, 103, 170-177. http://dx.doi.org/10.1111/j.1572-0241.2007.01524.x
[5]	McKeage, K., Plosker, G.L. and Siddiqui, M.A. (2006) Lubiprostone. Drugs, 66, 873-879. http://dx.doi.org/10.2165/00003495-200666060-00015
[6]	Barish, C.F., Drossman, D., Johanson, J.F. and Ueno, R. (2010) Efficacy and Safety of Lubiprostone in Patients with Chronic Constipation. Digestive Diseases and Sciences, 55, 1090-1097. http://dx.doi.org/10.1007/s10620-009-1068-x
[7]	Longstreth, G.F., Thompson, W.G., Chey, W.D., Houghton, L.A., Mearin, F. and Spiller, R.C. (2006) Functional Bowel Disorders. Gastroenterology, 130, 1480-1491. http://dx.doi.org/10.1053/j.gastro.2005.11.061
[8]	Agachan, F., Chen, T., Pfeifer, J., Reissman, P. and Wexner, S.D. (1996) A Constipation Scoring System to Simplify Evaluation and Management of Constipated Patients. Diseases of the Colon Rectum, 39, 681-685. http://dx.doi.org/10.1007/BF02056950
[9]	Lacy, B.E. and Levy, L.C. (2008) Lubiprostone: A Novel Treatment for Chronic Constipation. Journal of Clinical Interventions in Aging, 3, 357-364.
[10]	Camilleri, M., Bharucha, A.E., Ueno, R., Burton, D., Thomforde, G.M., Baxter, K., McKinzie, S. and Zinsmeister, A.R. (2006) Effect of a Selective Chloride Channel Activator, Lubiprostone, on Gastrointestinal Transit, Gastric Sensory, and Motor Functions in Healthy Volunteers. American Journal of Physiology-Gastrointestinal and Liver Physiology, 290, G942-G947. http://dx.doi.org/10.1152/ajpgi.00264.2005
[11]	Gras-Miralles, B. and Cremonini, F. (2013) A Critical Appraisal of Lubiprostone in the Treatment of Chronic Constipation in the Elderly. Journal of Clinical Interventions in Aging, 8, 191-200.
[12]	Huang, X., Zhang, S., Fan, Y.H. and Meng, L.N. (2012) Itopride Therapy for Functional Dyspepsia: A Meta-Analysis. World Journal of Gastroenterology, 18, 7371-7377. http://dx.doi.org/10.3748/wjg.v18.i48.7371
[13]	Suzuki, H., Nishizawa, T. and Hibi, T. (2006) Therapeutic Strategies for Functional Dyspepsia and the Introduction of the Rome III Classification. Journal of Gastroenterology, 41, 513-523. http://dx.doi.org/10.1007/s00535-006-1847-5