Fixed Dose Combination of Magaldrate Plus Domperidone Is More Effective than Domperidone Alone in the Treatment of Patients with Gastroesophageal Reflux Symptoms: A Randomized Double-Blind Study

DOI: 10.4236/pp.2014.52028   PDF   HTML     4,515 Downloads   6,775 Views   Citations

Abstract

Gastroeophageal reflux is a condition in which the acidified liquid content of the stomach backs up into the esophagus. The antiacid magaldrate and prokinetic domperidone are two drugs clinically used for the treatment of gastroesophageal reflux symptoms. However, the evidence of a superior effectiveness of this combination in comparison with individual drugs is lacking. A double-blind, randomized and comparative clinical trial study was designed to characterize the efficacy and safety of a fixed dose combination of magaldrate (800 mg)/domperidone (10 mg) against domperidone alone (10 mg), in patients with gastroesophageal reflux symptoms. One hundred patients with gastroesophageal reflux diagnosed by Carlsson scale were randomized to receive a chewable tablet of a fixed dose of magaldrate/domperidone combination or domperidone alone four times each day during a month. Magaldrate/domperidone combination showed a superior efficacy to decrease global esophageal (pyrosis, regurgitation, dysphagia, hiccup, gastroparesis, sialorrhea, globus pharyngeus and nausea) and extraesophageal (chronic cough, hoarseness, asthmatiform syndrome, laryngitis, pharyngitis, halitosis and chest pain) reflux symptoms than domperidone alone. In addition, magaldrate/domperidone combination improved in a statistically manner the quality of life of patients with gastroesophageal reflux respect to monotherapy, and more patients perceived the combination as a better treatment. Both treatments were well tolerated. Data suggest that oral magaldrate/domperidone mixture could be a better option in the treatment of gastroesophageal reflux symptoms than only domperidone.

Share and Cite:

S. Rodríguez-Sánchez, H. Rocha-González, C. Valle-Laisequilla, J. Rodríguez-Silverio, F. Flores-Murrieta and J. Reyes-García, "Fixed Dose Combination of Magaldrate Plus Domperidone Is More Effective than Domperidone Alone in the Treatment of Patients with Gastroesophageal Reflux Symptoms: A Randomized Double-Blind Study," Pharmacology & Pharmacy, Vol. 5 No. 2, 2014, pp. 216-223. doi: 10.4236/pp.2014.52028.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] S. J. Spechler, “Epidemiology and Natural History of Gastro-Oesophageal Reflux Disease,” Digestion, Vol. 51, No. 1, 1992, pp. 24-29.
http://dx.doi.org/10.1159/000200911
[2] Y. K. Wang, W. H. Hsu, S. S. Wang, et al., “Current Pharmacological Management of Gastroesophageal Reflux Disease,” Gastroenterology Research and Practice, Vol. 2013, 2013, Article ID: 983653.
[3] D. A. Revicki, M. Wood, P. N. Maton, et al., “The Impact of Gastroesophageal Reflux Disease on Health-Related Quality of Life,” American Journal of Medicine, Vol. 104, No. 3, 1998, pp. 252-258.
http://dx.doi.org/10.1016/S0002-9343(97)00354-9
[4] J. Tack, A. Becher, C. Mulligan, et al., “Systematic Review: The Burden of Disruptive Gastro-Oesophageal Reflux Disease on Health-Related Quality of Life,” Alimentary Pharmacology & Therapeutics, Vol. 35, No. 11, 2012, pp. 1257-1266.
http://dx.doi.org/10.1111/j.1365-2036.2012.05086.x
[5] R. C. Heading, “Epidemiology of Oesophageal Reflux Disease,” Scandinavian Journal of Gastroenterology Supplement, Vol. 168, 1989, pp. 33-37.
[6] H. B. El-Serag, S. Sweet, C. C. Winchester, et al., “Update on the Epidemiology of Gastro-Oesophageal Reflux Disease: A Systematic Review,” Gut, 2013, in Press.
http://dx.doi.org/10.1136/gutjnl-2012-304269
[7] G. Salis, “Revisión Sistemática: Epidemiología de la Enfermedad por Reflujo Gastroesofágico en Latinoamérica,” Acta Gastroenterol Latinoam, Vol. 41, 2011, pp. 60-69.
[8] B. van Pinxteren, K. E. Sigterman, P. Bonis, et al., “Short-Term Treatment with Proton Pump Inhibitors, H2-Receptor Antagonists and Prokinetics for Gastro-Oesophageal Reflux Disease-Like Symptoms and Endoscopy Negative Reflux Disease,” Cochrane Database of Systematic Reviews, Vol. 11, 2010, Article ID: CD002095.
[9] J. P. Henry, A. Lenaerts and G. Ligny, “Diagnosis and Treatment of Gastroesophageal Reflux in the Adult: Guidelines Recommended by French and Belgian Consensus,” Revue Médicale de Bruxelles, Vol. 22, 2001, pp. 27-32.
[10] J. P. Moraes-Filho, “Refractory Gastroesophageal Reflux Disease,” Arquivos de Gastroenterologia, Vol. 49, No. 4, 2012, pp. 296-301.
http://dx.doi.org/10.1590/S0004-28032012000400012
[11] D. Sifrim and F. Zerbib, “Diagnosis and Management of Patients with Reflux Symptoms Refractory to Proton Pump Inhibitors,” Gut, Vol. 61, No. 9, 2012, pp. 1340-1354. http://dx.doi.org/10.1136/gutjnl-2011-301897
[12] R. Fass, “Therapeutic Options for Refractory Gastroesophageal Reflux Disease,” Journal of Gastroenterology and Hepatology, Vol. 27, No. S3, 2012, pp. 3-7.
http://dx.doi.org/10.1111/j.1440-1746.2012.07064.x
[13] D. Ang, K. Blondeau, D. Sifrim, et al., “The Spectrum of Motor Function Abnormalities in Gastroesophageal Reflux Disease and Barrett’s Esophagus,” Digestion, Vol. 79, No. 3, 2009, pp. 158-168.
http://dx.doi.org/10.1159/000210265
[14] A. Broekaert, “Effect of Domperidone on Gastric Emptying and Secretion,” Postgraduate Medical Journal, Vol. 55, 1979, pp. 11-14.
[15] I. Soykan, I. Sarosiek, J. Shifflett, et al., “Effect of Chronic Oral Domperidone Therapy on Gastrointestinal Symptoms and Gastric Emptying in Patients with Parkinson’s Disease,” Movement Disorders, Vol. 12, No. 6, 1997, pp. 952-957. http://dx.doi.org/10.1002/mds.870120618
[16] J. A. Barone, “Domperidone: A Peripherally Acting Dopamine2-Receptor Antagonist,” Annals of Pharmacotherapy, Vol. 33, No. 4, 1999, pp. 429-440.
http://dx.doi.org/10.1345/aph.18003
[17] M. C. Champion, M. Hartnett and M. Yen, “Domperidone, a New Dopamine Antagonist,” CMAJ, Vol. 135, 1986, pp. 457-461.
[18] J. E. Valenzuela, “Effects of Domperidone on the Symptoms of Reflux Esophagitis,” In: G. Towse, Ed., Progress with Domperidone, a Gastrokinetic and Anti-Emetic Agent, Royal Society of Medicine International Congress and Symposium Ser, No 36, The Royal Society of Medicine, 1981, pp. 51-56.
[19] S. Ndraha, “Combination of PPI with a Prokinetic Drug in Gastroesophageal Reflux Disease,” Acta Medica Indonesiana, Vol. 43, 2011, pp. 233-236.
[20] N. Hunchaisri, “Treatment of Laryngopharyngeal Reflux: A Comparison between Domperidone Plus Omeprazole and Omeprazole Alone,” Journal of the Medical Association of Thailand, Vol. 95, 2012, pp. 73-80.
[21] E. Masci, P. A. Testoni, S. Passaretti, et al., “Comparison of Ranitidine, Domperidone Maleate and Ranitidine + Domperidone Maleate in the Short-Term Treatment of Reflux Oesophagitis,” Drugs under Experimental and Clinical Research, Vol. 11, 1985, pp. 687-692.
[22] A. Carroccio, G. Iacono, G. Montalto, et al., “Domperidone Plus Magnesium Hydroxide and Aluminum Hydroxide: A Valid Therapy in Children with Gastroesophageal Reflux. A Double-Blind Randomized Study versus Placebo,” Scandinavian Journal of Gastroenterology, Vol. 29, No. 4, 1994, pp. 300-304.
http://dx.doi.org/10.3109/00365529409094839
[23] J. N. Blackwell and R. C. Heading, “Effects of Domperidone on Lower Esophageal Sphincter Pressure and Gastroesophageal Reflux in Patients with Peptic Esophagitis,” Royal Society of Medicine International Congress and Symposium Series, Vol. 36, 1981, pp. 57-65.
[24] E. G. Giannini, P. Zentilin, P. Dulbecco, et al., “A Comparison between Sodium Alginate and Magaldrate Anhydrous in the Treatment of Patients with Gastroesophageal Reflux Symptoms,” Digestive Diseases and Sciences, Vol. 51, No. 11, 2006, pp. 1904-1909.
http://dx.doi.org/10.1007/s10620-006-9284-0
[25] R. Carlsson, J. Dent, E. Bolling-Sternevald, et al., “The Usefulness of a Structured Questionnaire in the Assessment of Symptomatic Gastroesophageal Reflux Disease,” Scandinavian Journal of Gastroenterology, Vol. 33, No. 10, 1998, pp. 1023-1029.
http://dx.doi.org/10.1080/003655298750026697
[26] World Medical Association Inc., “Declaration of Helsinki-Ethical Principles for Medical Research Involving Human Subjects,” 2013.
http://www.wma.net/en/30publications/10policies/b3/
[27] D. S. Pritchard, N. Baber and T. Stephenson, “Should Domperidone Be Used for the Treatment of Gastro-Oesophageal Reflux in Children? Systematic Review of Randomized Controlled Trials in Children Aged 1 Month to 11 Years Old,” British Journal of Clinical Pharmacology, Vol. 59, No. 6, 2005, pp. 725-729.
http://dx.doi.org/10.1111/j.1365-2125.2005.02422.x
[28] R. Clara, “Chronic Regurgitation and Vomiting Treated with Domperidone. A Multicenter Evaluation,” Acta Neurologica Belgica, Vol. 32, 1979, pp. 203-207.
[29] L. De Loore and H. Van Ravenstayn, “Domperidone Drops in the Symptomatic Treatment of Chronic Paediatric Vomiting and Regurgitation. A Comparison with Metoclopramide,” Postgraduate Medical Journal, Vol. 55, 1979, pp. 40-42.
[30] M. C. Vieira, N. I. Miyague, K. Van Steen, et al., “Effects of Domperidone on QTc Interval in Infants,” Acta Paediatrica, Vol. 101, No. 5, 2012, pp. 494-496.
http://dx.doi.org/10.1111/j.1651-2227.2012.02593.x
[31] L. M. Hondeghem, “Domperidone: Limited Benefits with Significant Risk for Sudden Cardiac Death,” Journal of Cardiovascular Pharmacology, Vol. 61, No. 3, 2013, pp. 218-225.
http://dx.doi.org/10.1097/FJC.0b013e31827afd0d
[32] S. C. Reddymasu, I. Soykan and R. W. McCallum, “Domperidone: Review of Pharmacology and Clinical Applications in Gastroenterology,” The American Journal of Gastroenterology, Vol. 102, No. 9, 2007, pp. 2036-2045.
http://dx.doi.org/10.1111/j.1572-0241.2007.01255.x
[33] J. M. Van Nueten, C. Ennis, L. Helsen, et al., “Inhibition of Dopamine Receptors in the Stomach: An Explanation of the Gastrokinetic Properties of Domperidone,” Life Sciences, Vol. 23, No. 5, 1978, pp. 453-457.
http://dx.doi.org/10.1016/0024-3205(78)90152-2
[34] T. Takahashi, S. Kurosawa, J. W. Wiley, et al., “Mechanism for the Gastrokinetic Action of Domperidone. In Vitro Studies in Guinea Pigs,” Gastroenterology, Vol. 101, 1991, pp. 703-710.
[35] C. Baur, A. Becker, R. Linder, et al., “Neutralizing Capacity, Pepsin Inactivation and Binding to Bile Acids and Lysolecithin of the Antacid Magaldrate,” Arzneimittelforschung, Vol. 31, 1981, pp. 504-507.
[36] D. F. McCafferty and A. D. Woolfson, “A Comparative Assessment of a New Antacid Formulation Based on Magaldrate,” Clinical and Hospital Pharmacy, Vol. 8, No. 4, 1983, pp. 349-355.
[37] L. E. Borella, J. F. DiJoseph and G. N. Mir, “Cytoprotective and Antiulcer Activities of the Antacid Magaldrate in the Rat,” Arzneimittelforschung, Vol. 39, 1989, pp. 786-789.
[38] C. Schmidt, B. Baumeister, J. Kipnowski, et al., “Magaldrate Stimulates Endogenous Prostaglandin E2 Synthesis in Human Gastric Mucosa in Vitro and in Vivo,” Hepatogastroenterology, Vol. 45, 1998, pp. 2443-2446.
[39] A. V. Patel, D. D. Santani and R. K. Goyal, “Antiulcer Activity and the Mechanism of Action of Magaldrate in Gastric Ulceration Models of Rat,” Indian Journal of Physiology and Pharmacology, Vol. 44, 2000, pp. 350-354.

  
comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.