Effect of long-term lansoprazole therapy on serum vitamin B12 levels in veteran patients with gastroesophageal reflux disease

GERD (52.1% GI v/s 52.7% PCP ). 91% of GI physicians would treat severe esophagitis with standard dose proton pump inhibitor (PPI) as compared to 63% of PCP s. (p= 0.03). All the GI physicians would treat a patient with Non-dysplastic Barretts esophagus (NDBE) with a standard dose PPI as compared to 61% of PCP s. (p=O.O01). The PCP's and the GI physicians used EGg for evaluation of complicated GERD to the same extent (81.8% GI v/s 75.9% PCP ). 43% of GI physicians would do surveillance EGD for NDBE in 2-3 years as compared to 13% of the PCP s. (p=0.61). However an equal number of the GI physicians would repeatthe EGD in 6 months. CONCLUSIONS:There are differences according to specialty tn the reported management of uncomplicated and complicated GERD. In addition there is considerable variability in the use of diagnostic EGD for endoscopic surveillance of NDBE with a large number of GI physicians not following the recommended guidelines. Further studies should examine the underlying reasons for the disparities and determine if these differences are present in actual clinical settings.

2232 Effect of Long-Term Lansoprazole Therapy on Seram Vitamin 812 Levels in Veteran Patients with Gaatroesophageal Reflux Disease Joseph P. Reilly, Arnold and Marie Schwartz College of Pharmacy, Long Island University, Brooklyn, NY; Edmund J. Bini, Christopher G. Sotiriou, VA New York Harbor Healthcare System, New York, NY; Henry Cohen, Kingsbrook Jewish Medical Ctr, Brooklyn, NY; Loay Salman, VA New York Harbor Healthcare System, New York, NY BACKGROUND:Gastric acid plays an important role in the complex process of vitamin B12 absorption. Proton pump inhibitors significantly raise gastric pH and have been shown to impair the absorption of vitamin 812. Long-term therapy with proton pump inhibitors may decrease serum vitamin B12 levels and resuit in anemia. The aim of this study is to determine the effect of long-term lansoprazole therapy on serum vitamin B12 levels in veteran patients with gastroesophagealreflux disease (GERD). METHODS:Patients over 55 years of age taking lansoprazole for at least 18 months for GERD were prospectively identified. An age-matched cohort of patients who were not taking lansoprazole served as controls. After a thorough history and physical examination, serum vitamin B12 levels, fotic acid, and a complete blood count were obtained from all patients enrolled. Any patient taking a medication or having a condition that is known to affect the measured parameters was excluded. RESULTS: There was no significant difference in the mean age of the patients in the lansoprezolegroup (n = 31) and control group (n=31) [63.7 -+ 7.2 years vs. 65.4 -+ 7.3 years, P = 0.36]. The mean duration of lansoprazoletherapy was 22.3 _+ 3.1 months. The mean serum vitamin B12 levels in the lansoprazole and control groups were not significantly different (322.7 -+ 75.8 vs. 331.6 -+ 80.2 pg/mL, P = 0.66). There were no significant differences in folic acid levels between the lansoprazole and control groups (12.0 -+ 3.0 vs. 12.6 -+ 3.0 ng/mL, P = 0.42). No patient evaluated had anemia. CONCLUSION:The use of lansoprazole in veteran patients with GERDdoes not appear to significantly decreaseserum vitamin B12 levels. These findings suggest that routine monitoring of serum vitamin 612 levels in this population is not warranted in patients taking long-term lansoprazole therapy for GERD.

which pantoprazole was taken successively, were counted. In addition, patients had access to the antacid magaldrate as rescue medication for which the consumption was assessed by tablet count. The prFmary efficacy variable was the rate of patients (non-responders) who were unwilling to continue the therapy due to an inadequate relief of symptoms. Additionally, patients were asked to judge the efficacy of treatment. Results:In an interim-analyses the data obtained from 55 patients (23 male, 32 female, mean age 56.8 +_ 17.9 years) were analyzed. After the acute phase symptom relief of heartburn and acid regurgitation could be observed in 94.5% and 82.5% of patients, respectively. For the subsequent long-term phase of the study 51 patients were eligible. During the first 3 months of the long-term phase a mean number of 22.6 pantoprazole tablets (0.27 tablets/day) were taken. During this on-demand pariod 7.2 episodes of continuous pantoprazole intake could be observed. At each episode 2.8 tablets of pantoprazole were taken on average. Additionally, patients took a total mean number of 24.7 tablets of magaldrate (0.29 tablets/day) as rescue medication during the 3 months. After the acute phase 96.3% of patients and after the subsequent 3 months 96.0% of patients experiencadan improvement of complaints and judged the treatment as sufficient. Finally, 100% of patients who took part in the long-term phase were willing to continue the study for a further 3 months. Adverse events were experienced by 29% of patients, which were considered to be unrelated to the study medication in most cases. Conclusion:It could be shown that on-demand therapy with PANTO 20 mg is an effective treatment strategy in patients with mild GERD and was well tolerated and safe.

Interim Analysis of POE Trial, the Pantoprazole/OmeprezoleEquivalence Trial. Healing of Lesions in Patients with Gastroesophageal Reflex Disease II/]11after 4 weeks nt Treatment with Pantoprazole 40 mg or Omeprazole 40 mg Once Daily Thomas Koemer, Zentralklinikum Suedthueringen Suhl, Suhl Germany; Kurt Schuetze, Hanusch-Krankenhaus,Wien Austria; Ruud Jm Van Leendert, Albert Schweitzer Ziekenhuis, Zwijndrecht Netherlands; Luis Novais, Hosp F Fonseca, Amedora Portugal; Martina Bohuschke, Byk Gulden GmbH, Konstanz Germany; And The Poetrial Study Group Objective In this multinational randomised double-bliod study we compared the efficacy of Pantoprazole40 mg (P) and omeprazole40 mg (0) in healing of patients with gastroesophageal reflux disease (GERD) II or III (acc. Savary/Miller modified by Siewert). The interim analysis comprises data of the first 300 patients focussing on the healing rate after 4 weeks of treatment. Results The ITr population consists of 279 patients, 143 in the pantoprazole and 136 in the omeprazole group. Demography:The P group consisted of 55 female and 88 male patients whereas in the 0 group 63 female and 70 male patients participated.The data of the baseline charenteristics show a homogenous population over both treatment groups. The mean age in the P group was 53.3 years ranging from 19.3 to 86.2 years and 54.8 years in the 0 group with a range from 19.4 to 85.0 years. The mean body mass index in the P group was 26.8 and 26.1 in the 0 group. Efficacy:The overall healing rate in both treatment groups (IT], n = 279) was 68%. The overall healing rates in patients with GERD II were 72%. The efficacy in healing after 4 weeks of treatment were approximately the same in both treatment groups. Pantoprazole reached 69% and omeprazole 66% healing rates with no statistical difference between each other. Due to the low number of patients with GERD III (17%) only for GERD II pa'dents(n = 238) the healing rates were analysed separately. In the pantoprazole group 75% and in the omeprazole group 69% of the patients were cured. However, this numerical difference was not statistically significant. Safety:62 Adverse events (AEs) occurred during the first 4 weeks of treatment. The number of AEs was 30 in 21 patients in the pantoprazole group and 32 in 20 patients in the omeprazole group, respectively. In both groupsthe investigator considered the majority as unlikely related or unrelated to the study medication. Conclusion In the interim analysis of 279 GERD II/lll patients recruited in Germany the single dose of 40 mg daily showed equivalent efficacy of pantoprazole and omeprazole in the healing of oesephagitis after 4 weekstreatment. Also the safety profile of both substances was comparable.

2233 Nocturnal Acid Control with Farnotidine 10 rag/Antacid 21 mEq ANC Combination In Subjects on Daily Omeprazole Scott H. Korn, Joyce D. King, Laura A. Stauffer, Merck Research Lab, West Point, PA; Mary Frances Rack, Frank L. Lanza, Houston Institute for Clin Research, Houston, TX BACKGROUND:Patients taking a single daily dose of proton-pump inhibitors often experience breakthrough symptoms that are treated with nonprescription (OTC) products. This crossover study compared the pharmacodynamic profile of an evening dose of 2 OTC famotidine formulations with that of omeprazole and placebo in 24 subjects taking omeprazole 20 mg each morning throughout the study. METHODS:Each subject received a single evening dose of the FACT combination tablet (famotidine 10 m g + antacid 21 mEq calcium carbonatemagnesium hydroxide), famotidine 10 mg, omeprazole 20 rag, and placebo, in a randomly assigned sequence of four treatment periods. Each period began with insertion of a gastric pH probe, ingestion of a standard high-fat meal, a 3-hour postprandial monitoring period, administration of study medication, and monitoring of gastric pH for an additional 20 hours. A standard breakfast and lunch were eaten. RESULTS: Over the O- to 9.5-hour postdose period the mean area under the intragastdc pH vs. time curve was greatest with FACT. Mean gastric pH with famotidine 10 mg and omeprazole 20 mg was significantly lower by 0.7 to 0.9 pH units, respectively, when compared to FACT (p = 0.027, p = 0.003, respectively). The difference between famotidine and omeprazole was not significant. During the O- to 2-hour postdose period, FACTproduced a greater increase in gastric pH (lower acidity) than omeprazole 20 mg (p =0.007), famotidine 10 mg (p=0.018), or placebo (p=O.O02), as measured by mean change from baseline for intragastric pH. CONCLUSION:An evening dose of FACT reduced gastric acidity more quickly and to a greater extent than omeprazole 20 mg, famotidine 10 mg, or placebo in subjects taking omeprazole 20 mg each morning.

2236 Continuous Maintenance Therapy With Omeprazole For More Than 10 Years In Patients With Severe Peptic Ulcer Or Reflex Esophagitis Disease (13 - 17 Years) Gorig Brunner, Chdstoph Athmann, Univ Medical Sch, Hannover Germany; Regina Lamberts, Univ of Tuebingen, Tuebingen Germany; N Havu, G Olsson, AstraZeneca, Soedertaelje Sweden; Anders Walan, AstraZeneca, Moelndal Sweden; Werner Creutzfeldt, Georg August Univ, Gneffingen Germany Between 1983 and 1987 143 patients with severe peptic ulcer disease or gastroesophageal reflux disease resistant to or ineligible for surgery and/or high dose ranitidine treatment, were admitted to omeprazole Ioog-term maintenance therapy after initial healing of their peptic lesions. The patients have been tightly monitored with regular endoscopies, gastric biopsies, and laboratory tests. Dosing of omeprazole was adjusted individually with a daily dose ranging from 20 mg every second day to 80 mg daily (mean 41 -+18 mg). Omeprazole maintenance therapy was very well tolerated. There were no severe clinical symptoms during these years necessitating termination of therapy. Laboratory values did not indicate any negative influences from continuous treatment with omeprazole. Mean serum gastrin concentration increased from 79 pg/ml to 141 pg/ml during the first three months with no further increase. The ECLcell density in the corpus mucosa increased from 0.3 to 0.5 %. ECL-cell hyperplasia was mainly seen in Hp-positive patients, more advanced grades almost only in older patients. No dysplasia or carcinoids were seen. Gastric morphology remained normal in I-Ip-negative patients. In Hp-positive patients antral gastritis significantly improved while gastritis in the deep oxyntic mucosa worsened with concomitant increase in the extent and prevalence of gastric glandular atrophy. 7 out of 15 patients with advanced liver cirrhosis and severe portal hypertension, who received omeprazole maintenance therapy because of reflux disease after sclerotherapy of bleeding varices developed large benign hyperplastic polyps in the gastric antrum between 6 to 18 months after start of therapy. The mean omeprazole dose in patients with liver cirrhosis was 39 rag. The mechanism of polyp development is under further investigation. Recurrences of peptic ulcers and reflux oesophagifis were rare and could be healed with dose increases. Conclusion: Omeprazole long term maintenance therapy for up to 17 years is effective and safe. The recurrence rate during continuous maintenancetreatment

2234 On-Demand Therapy with Pantoprazole 20 mg O.D. (PANTO)for the Long-Term Management of GERD Patients Previously Healed from Hearthura Theo Scholten, Medical Clin Hosp, Hagen Germany; Gudrun Gel:z, Peter Sander, Byk Gulden GmbH, Konstanz Germany Aim: Investigation of symptom-directed demand on acid inhibitory therapy after successful treatment of mild GERD. Methods:in this open on-demand study it was planned to enroll 250 patients with endoscopically confirmed mild GERD stage 0 or I. The patients were initially treated with PANTO 20 mg for 4 weeks (acute phase). Subsequently, those patients who were healed on the condition of being free from heartburn, entered the long-term phase (6 months). These patients received PANTO in EDEM-containers (electronic drug exposure monitor). Patients were told to take the study medication on demand on recurrence of symptoms, primarily heartburn. The total number of tablets per day and the number of episodes, on

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