Evaluation Of Safety And Efficacy Of Pantoprazole And Domperidone Combination In Patients With Gastroesophageal Reflux Disease

摘要

Background: Gastro-esophageal reflux disease (GERD) and non ulcer dyspepsia (NUD) are overlapping disorders with common symptomatology. The combination is synergistic by decreasing acid production as well as increasing lower esophageal tone & esophageal clearance thus producing a better therapeutic response. Objective: To evaluate the safety and efficacy of the combination Methods: In patients satisfying the inclusion and exclusion criteria for GERD (Group A, n=105) and Non Erosive GERD (Group B, n=19) baseline symptomatology, endoscopy & laboratory investigations were done followed by test medication once daily for 28 days & monitored for symptom improvement at week 1, 2, & 4 and endoscopy and laboratory investigations at week 4. Results: Of Group A patients having erosive GERD 68/94 (72.34%) were completely cured, 19/94 (20.21%) partially cured, 7/94 (7.44%) not cured. All patients having Non-Erosive GERD had significant improvement in symptoms at 4 week from baseline. Conclusion: Combination of pantoprazole and domperidone is a effective & safe combination with high symptom improvement rates. Introduction GERD is one of the commonest esophageal disorder, with overlapping symptomatology with NUD. Erosive GERD is differentiated from functional dyspepsia by positive endoscopic findings but there is a considerable overlap between functional dyspepsia & non-erosive reflux disease. There is a controversy with regard to whether symptoms of heartburn & acid regurgitation should be considered as a part of NUD or not. Rome II definition considers them to be indicative of GERD whereas others believe them to be a part of dyspepsia1. We believe these to be a spectrum of disease with some patients having erosive esophagitis and others not but most having common symptoms. The basic mechanisms underline the spectrum are –increased acid production, decreased tone of lower esophageal sphincter (LES) & disturbances in gut motility. In fact, National Disease and Therapeutic Index data (U.S.A.) has shown that physicians are writing more than 20% of omeprazole and lansoprazole prescriptions in combination with other medications, including H2RAs and prokinetic agents, or for twice-daily administration, in an effort to combat difficult cases of acid reflux.2 With respect to reports with combination of anti-secretory with prokinetics in GERD & NUD from India, study by Madan et al. has shown that combination of pantoprazole and mosapride has better symptomatic relief than pantoprazole alone in cases of GERD whereas healing rates are similar.3 Another such study comparing ranitidine and domperidone with ranitidine alone has found better symptom improvement with the combination.4 We designed the study with an objective to evaluate the therapeutic efficacy and safety of combination of pantoprazole with domperidone in management of GERD. Materials And Methods The study was an open-label, non-comparative, non-randomized study carried out in 3 large medical college hospitals and one specialist digestive disease hospital in India during September 2003 to march 2004. Informed consent was obtained from the patients & the study was in accordance with the clinical principles laid down in declaration of Helsinki. A minimum of 100 subjects were to be enrolled at 4 centers to account for dropouts a total of 124 patients were recruited for the study. Inclusion CriteriaPatients of either sex 18 yrs or more willing to give informed consentPatients endoscopically classified according to modified Hetzel-Dent grade 1-3 esophagitis5.Grade 0- no mucosal abnormality; Grade 1- no macroscopic erosions but erythema, hyperemia/mucosal friability; Grade 2- superficial erosion involving 1. (None) no symptoms: 2. (mild) symptoms can be easily ignored: 3. (mod) awareness of symptoms but easily tolerated: 4. (severe) symptoms sufficient enough to cause interference with normal activities: 5. (incapacitating) inability to perform daily activities and/or require days off work. The q