Omeprazole: a pharmacoeconomic evaluation of its use in duodenal ulcer and reflux oesophagitis

Omeprazole regulates gastric acid secretion and is an effective treatment of acute duodenal ulcer and reflux oesophagitis, achieving more rapid healing and symptomatic relief than histamine H 2-receptor antagonists. When administered as maintenance therapy, omeprazole reduces the incidence of relapse. The drug is also highly effective in patients poorly responsive to histamine H 2-receptor antagonists. The daily acquisition cost of omeprazole is higher than that of histamine H 2-receptor antagonists in many countries, and thus it is important to evaluate the pharmacoeconomic impact of omeprazole in the short and long term treatment of duodenal ulcer and reflux oesophagitis. Pharmacoeconomic analyses have been performed in several clinical settings using pooled data from clinical trials or simulated models of clinical practice. In a single analysis using Finnish cost data, omeprazole was more cost effective than ranitidine in the treatment of duodenal ulcer disease over a 6-month period. The cost effectiveness of omeprazole was comparable to that of sucralfate-containing regimens, with patients receiving omeprazole being healed more quickly and experiencing a greater number of healthy days. Using a computer-model simulation and Swedish cost data, omeprazole was more cost effective than ranitidine when administered as intermittent treatment of duodenal ulcer over 5 years. Preliminary reports indicate that regimens which eradicate Helicobacter pylori are more cost effective than those which do not. As short term treatment of reflux oesophagitis, omeprazole 20 to 40 mg/day was the dominating treatment strategy, being less costly and more effective than ranitidine 300 to 1200 mg/day. Omeprazole 20 mg/day produced symptom-free days more cost effectively than either cimetidine 1.6 g/day or ranitidine 300 mg/day. More importantly, as long term (maintenance or intermittent) treatment of reflux oesophagitis, omeprazole 20 mg/day was more cost effective than both ranitidine 150 mg twice daily and 'phase 1' therapy (diet and antacids) over 6 and 12 months. Thus, based on analyses evaluated, omeprazole appears to be more cost effective than ranitidine in the short term treatment of duodenal ulcer. Results for long term treatment are less clear cut, but full details from some studies are not yet available. For the short term treatment of reflux oesophagitis omeprazole is more cost effective than ranitidine or cimetidine and for long term treatment omeprazole is more cost effective than ranitidine. As treatment for reflux oesophagitis, omeprazole is considered to be the dominating treatment strategy.     

Decision analysis of histamine H2-receptor antagonist maintenance therapy versus Helicobacter pylori eradication therapy: a randomised controlled trial in patients with continuing pain after duodenal ulcer

BACKGROUND: Much has been published on the efficacy and cost effectiveness of Helicobacter pylori eradication treatment as an alternative to histamine H2-receptor antagonist maintenance treatment in peptic ulcer disease. However, most studies have analysed and emphasised H. pylori eradication rates rather than management/control of symptoms and the associated cost savings. Although H. pylori eradication therapy is very successful in clearing the infection, dyspeptic symptoms may persist and management of these can be expensive. OBJECTIVE: The aim of this study was to assess the cost implications in controlling symptoms using either H2-receptor antagonist maintenance therapy or H. pylori eradication therapy in patients with duodenal ulcer disease. DESIGN: This was a non-blind, prospective, randomised, parallel-group study comparing maintenance H2-receptor antagonist treatment using ranitidine with H. pylori eradication therapy, with a 1-year follow-up. SETTING: This was a study of outpatients from general practices in Dundee, Scotland, or the Ninewells Hospital, Dundee, gastroenterology clinic. PATIENTS AND PARTICIPANTS: 119 patients with confirmed duodenal ulcer, free from active ulceration at study entry but positive for H. pylori infection, who were receiving maintenance H2-receptor antagonist therapy. INTERVENTIONS: Patients were randomised to receive either continuing maintenance therapy with ranitidine (initially 150 mg daily; 58 patients) or H. pylori eradication therapy using an omeprazole/amoxicillin/metronidazole regimen (or omeprazole/clarithromycin if allergic to penicillin). MAIN OUTCOME MEASURES AND RESULTS: Overall, H. pylori eradication rates were 100% per protocol and 95.1% intention-to-treat. At completion of 1 year of follow-up, 12 of the 61 (19.7%) patients successfully eradicated of H. pylori were still dependent on acid suppression for symptom relief. H. pylori eradication treatment was the least-cost strategy in managing/controlling symptoms at 1 year (168 Pounds vs 210 Pounds per patient; 1996 values). However, over time, post-eradication treatment costs were greater than H2-receptor antagonist therapy costs. Any potential savings were directly related to the proportion of patients needing further treatment post-eradication, the cost of endoscopy and the urea breath test. CONCLUSIONS: If dyspepsia persists long term, H. pylori eradication treatment may not be the least-cost option for patients with duodenal ulcer.     

Lansoprazole: pharmacokinetics, pharmacodynamics and clinical uses

Lansoprazole (Prevacid, TAP Pharmaceuticals, Inc.) is a substituted benzimidazole that inhibits gastric acid secretion. This agent is approved for the short-term treatment of erosive reflux oesophagitis, active gastric ulcer, active duodenal ulcer and the treatment of non-steroidal anti-inflammatory drug (NSAID)-induced gastric and duodenal ulcers. It is also approved for the long-term treatment of healed reflux oesophagitis, healed duodenal ulcer, the treatment of hypersecretory conditions such as Zollinger-Ellison syndrome and the eradication of Helicobacter pylori as a component of triple therapy with lansoprazole, clarithromycin and amoxicillin, or dual therapy with lansoprazole and amoxicillin. Its mechanism of action is to selectively inhibit the membrane enzyme H+/K+ ATPase in gastric parietal cells. In clinical trials, lansoprazole is more effective than placebo or histamine (H2)-receptor antagonists in the treatment of reflux oesophagitis. Lansoprazole administered at a dose of 30 mg daily produced faster relief of symptoms and superior healing rates in patients with gastric or duodenal ulcers or reflux oesophagitis than H2-receptor antagonists. A daily dose of 30 mg lansoprazole reduced epigastric pain faster than omeprazole 20 mg daily in patients with peptic ulcer disease but healing rates at 4 and 8 weeks were similar with both agents at these dosages. Lansoprazole was more effective than H2-receptor antagonists in patients with Zollinger-Ellison syndrome and produced similar treatment outcome to omeprazole. Lansoprazole in combination with clarithromycin and amoxicillin produced similar rates of eradication of H. pylori. In clinical trials, lansoprazole is well-tolerated and has a low frequency of side effects similar to that of H2-receptor antagonists or omeprazole.     

Lansoprazole: pharmacokinetics,pharmacodynamics and clinical uses

Lansoprazole (Prevacid?, TAP Pharmaceuticals, Inc.) is a substituted benzimidazole that inhibits gastric acid secretion. This agent is approved for the short-term treatment of erosive reflux oesophagitis, active gastric ulcer, active duodenal ulcer and the treatment of non-steroidal anti-inflammatory drug (NSAID)-induced gastric and duodenal ulcers. It is also approved for the long-term treatment of healed reflux oesophagitis, healed duodenal ulcer, the treatment of hypersecretory conditions such as Zollinger-Ellison syndrome and the eradication of Helicobacter pylori as a component of triple therapy with lansoprazole, clarithromycin and amoxicillin, or dual therapy with lansoprazole and amoxicillin. Its mechanism of action is to selectively inhibit the membrane enzyme H⁺/K⁺ATPase in gastric parietal cells. In clinical trials, lansoprazole is more effective than placebo or histamine (H₂)-receptor antagonists in the treatment of reflux oesophagitis. Lansoprazole administered at a dose of 30 mg daily produced faster relief of symptoms and superior healing rates in patients with gastric or duodenal ulcers or reflux oesophagitis than H₂-receptor antagonists. A daily dose of 30 mg lansoprazole reduced epigastric pain faster than omeprazole 20 mg daily in patients with peptic ulcer disease but healing rates at 4 and 8 weeks were similar with both agents at these dosages. Lansoprazole was more effective than H₂-receptor antagonists in patients with Zollinger-Ellison syndrome and produced similar treatment outcome to omeprazole. Lansoprazole in combination with clarithromycin and amoxicillin produced similar rates of eradication of H. pylori. In clinical trials, lansoprazole is well-tolerated and has a low frequency of side effects similar to that of H₂-receptor antagonists or omeprazole.     

Lansoprazole. A review of its pharmacodynamic and pharmacokinetic properties and its therapeutic efficacy in acid-related disorders.

Lansoprazole is an effective acid pump inhibitor acting at the final enzymatic step of the acid secretory pathway of the parietal cell, decreasing gastric acid secretion regardless of the primary stimulus. Results of short term (less than 8 weeks) clinical trials have shown lansoprazole to be significantly superior to placebo and ranitidine in the treatment of duodenal ulcer, both in the rate of healing and in overall healing at 4 weeks. Lansoprazole appears to heal duodenal ulcer more quickly than famotidine, and demonstrates slightly greater efficacy at 4 weeks, although both drugs appear to have equivalent efficacy overall. Gastric ulcers and reflux oesophagitis are also healed by lansoprazole 30 mg/day for 4 to 8 weeks, with healing rates after 8 weeks of approximately 85 to 95% for both indications. Lansoprazole appears to be superior to ranitidine and comparable to omeprazole in treating reflux oesophagitis. Furthermore, lansoprazole has relieved reflux symptoms more quickly than either ranitidine or omeprazole. Preliminary data also indicate that lansoprazole may be effective in the treatment of peptic ulcer disease and reflux oesophagitis refractory to H2-receptor antagonists, and in patients with Zollinger-Ellison syndrome. While direct comparisons with omeprazole are limited, results suggest that lansoprazole, used for short term treatment, is at least as effective as omeprazole in the treatment of peptic ulcer and reflux oesphagitis. Lansoprazole has been well tolerated in short term clinical trials, with an incidence of adverse effects comparable with that of other agents in its therapeutic class. Trials assessing long term tolerability data are ongoing and will be required as part of the assessment of the safety profile, if lansoprazole is to be used prophylactically to prevent ulcer recurrence. Thus, by virtue of its ability to heal ulcers and rapidly relieve associated symptomatology, lansoprazole represents a useful alternative for the treatment of acid related disorders.     

Omeprazole. An updated review of its pharmacology and therapeutic use in acid-related disorders.

Omeprazole is the first of a new class of drugs, the acid pump inhibitors, which control gastric acid secretion at the final stage of the acid secretory pathway and thus reduce basal and stimulated acid secretion irrespective of the stimulus. In patients with duodenal or gastric ulcers, omeprazole as a single 20 mg daily dose provides more rapid and complete healing compared with ranitidine 150 mg twice daily or 300 mg at nighttime, or cimetidine 800 or 1000 mg/day. Patients poorly responsive to treatment with histamine H2-receptor antagonists respond well to omeprazole--most ulcers healed within 4 to 8 weeks of omeprazole 40 mg/day therapy. Omeprazole 20 or 40 mg/day has been administered as maintenance therapy for peptic ulcer disease for up to 5.5 years with very few ulcer recurrences. In patients with erosive or ulcerative oesophagitis, omeprazole 20 or 40 mg/day produces healing in about 80% of patients after 4 weeks, and is superior to ranitidine with respect to both healing and symptom relief. Healing rates of greater than 80% are achieved after 8 weeks in patients with severe reflux oesophagitis unresponsive to H2-receptor antagonists. Maintenance therapy with a daily 20 mg dose prevents relapse in about 80% of patients over a 12-month period. Omeprazole is considered to be the best pharmacological option for controlling gastric acid secretion in patients with Zollinger-Ellison syndrome. Daily dosages of 20 to 360 (median 60 to 70 mg successfully reduce basal acid output to target levels (less than 10 mmol/h or less than 5 mmol/h in patients with severe oesophagitis or partial gastrectomy) during treatment for up to 4 years. Omeprazole is well tolerated in short term studies (up to 12 weeks); the reported incidence of serious side effects (about 1%) being similar to that seen in patients treated with an histamine H2-receptor antagonist. The longer term tolerability of omeprazole has been investigated in patients treated for up to 5.5 years. Slight hyperplasia, but no evidence of enterochromaffin-like (ECL) cell dysplasia or neoplasia or ECL cell carcinoids has been reported. ECL cell carcinoids have been observed in rats after life-long treatment with high doses of omeprazole or ranitidine, or in rats with partial corpectomy; the weight of experimental evidence indicates that this is a result of prolonged hypergastrinaemia.(ABSTRACT TRUNCATED AT 400 WORDS)     

Lansoprazole: an update of its place in the management of acid-related disorders

Lansoprazole is an inhibitor of gastric acid secretion and also exhibits antibacterial activity against Helicobacter pylori in vitro. Current therapy for peptic ulcer disease focuses on the eradication of H. pylori infection with maintenance therapy indicated in those patients who are not cured of H. pylori and those with ulcers resistant to healing. Lansoprazole 30 mg combined with amoxicillin 1g, clarithromycin 250 or 500mg, or metronidazole 400 mg twice daily was associated with eradication rates ranging from 71 to 94%, and ulcer healing rates were generally >80% in well designed studies. In addition, it was as effective as omeprazole- or rabeprazole-based regimens which included these antimicrobial agents. Maintenance therapy with lansoprazole 30 mg/day was significantly more effective than either placebo or ranitidine in preventing ulcer relapse. Importantly, preliminary data suggest that lansoprazole-based eradication therapy is effective in children and the elderly. In the short-term treatment of patients with gastro-oesophageal reflux disease (GORD), lansoprazole 15, 30 or 60 mg/day was significantly more effective than placebo, ranitidine 300 mg/day or cisapride 40 mg/day and similar in efficacy to pantoprazole 40 mg/day in terms of healing of oesophagitis. Lansoprazole 30 mg/day, omeprazole 20 mg/day and pantoprazole 40 mg/day all provided similar symptom relief in these patients. In patients with healed oesophagitis. 12-month maintenance therapy with lansoprazole 15 or 30 mg/day prevented recurrence and was similar to or more effective than omeprazole 10 or 20 mg/day. Available data in patients with NSAID-related disorders or acid-related dyspepsia suggest that lansoprazole is effective in these patients in terms of the prevention of NSAID-related gastrointestinal complications, ulcer healing and symptom relief. Meta-analytic data and postmarketing surveillance in >30,000 patients indicate that lansoprazole is well tolerated both as monotherapy and in combination with antimicrobial agents. After lansoprazole monotherapy commonly reported adverse events included dose-dependent diarrhoea, nausea/vomiting, headache and abdominal pain. After short-term treatment in patients with peptic ulcer, GORD, dyspepsia and gastritis the incidence of adverse events associated with lansoprazole was generally < or = 5%. Similar adverse events were seen in long-term trials, although the incidence was generally higher (< or = 10%). When lansoprazole was administered in combination with amoxicillin, clarithromycin or metronidazole adverse events included diarrhoea, headache and taste disturbance. In conclusion, lansoprazole-based triple therapy is an effective treatment option for the eradication of H. pylori infection in patients with peptic ulcer disease. Preliminary data suggest it may have an important role in the management of this infection in children and the elderly. In the short-term management of GORD, lansoprazole monotherapy offers a more effective alternative to histamine H2-receptor antagonists and initial data indicate that it is an effective short-term treatment option in children and adolescents. In adults lansoprazole maintenance therapy is also an established treatment option for the long-term management of this chronic disease. Lansoprazole has a role in the treatment and prevention of NSAID-related ulcers and the treatment of acid-related dyspepsia; however, further studies are needed to confirm its place in these indications. Lansoprazole has emerged as a useful and well tolerated treatment option in the management of acid-related disorders.     

Systematic review: the effect of Helicobacter pylori and its eradication on gastro-oesophageal reflux disease in patients with duodenal ulcers or reflux oesophagitis

BACKGROUND: The effect of Helicobacter pylori in provoking or protecting against gastro-oesophageal reflux disease is unclear and studies have given conflicting results. Recent guidelines recommend H. pylori eradication in patients on long-term proton pump inhibitors. AIM: To ascertain the effect of H. pylori eradication on gastro-oesophageal reflux disease outcomes (reflux oesophagitis and heartburn) in patients with duodenal ulcer disease, and to ascertain the effect of H. pylori infection on reflux oesophagitis concerning heartburn, pH, severity, healing and relapse rates. METHODS: A systematic review of electronic databases was undertaken to September 2003. Experts in the field, pharmaceutical companies and journals were contacted about unpublished trials. Studies were reviewed according to predefined eligibility and quality criteria. Twenty-seven studies/trials were included in the systematic review. RESULTS: Study variation rather than therapy-influenced results in relation to the presence or absence of oesophagitis in patients with duodenal ulcer who underwent H. pylori eradication at 6-48 months follow-up. In patients with reflux oesophagitis no obvious differences were discovered in heartburn scores, 24-h pH values, healing and relapse rates between H. pylori-positive and -negative cases. CONCLUSION: There is no evidence to indicate that H. pylori eradication in duodenal ulcer disease provokes reflux oesophagitis or worsens heartburn; (ii) there are insufficient data to draw firm conclusions about the impact of H. pylori in patients with reflux oesophagitis.     

Formulary management of proton pump inhibitors

The management of dyspepsia has been radically altered by the discovery of the role of Helicobacter pylori and the advent of proton pump inhibitors (PPIs). The use of PPIs alone as antisecretory agents and as part of triple therapy regimens for H. pylori eradication accounts for a significant percentage of any healthcare system's drug budget. Thus, it is important to take into account a variety of factors when devising a formulary and considering which PPIs to include. Consideration of 3 factors are particularly crucial in this process, namely therapeutic efficacy, tolerability and cost but several other clinical and economic parameters should also be considered. The mechanisms of action of all 4 PPIs currently available (omeprazole, lansoprazole, pantoprazole and rabeprazole) are very similar, with any small differences in pharmacological properties unlikely to be of clinical significance. Therapeutic efficacy in patients with acute reflux oesophagitis is again very similar for all 4 PPIs at their standard dosages; all agents are superior to H2-antagonists. Data on maintenance therapy for reflux oesophagitis also suggest similar efficacy for omeprazole and lansoprazole; data on pantoprazole and rabeprazole are awaited. For the treatment of H. pylori-related ulcers, the consensus at present is for PPI-based triple therapy. Again, all PPIs seem equally efficacious for this indication but pantoprazole and rabeprazole have yet to receive licences for H. pylori eradication therapy (HPET) in most countries. Drug tolerability is another critical issue to consider in formulary inclusion decisions. As a class, the PPIs are well tolerated. Minor drug interactions are reported for omeprazole, lansoprazole and rabeprazole but not for pantoprazole. However, whether or not this is significant in clinical practice is open to debate. Most of the pharmacoeconomic data in these indicators, to date, relate to omeprazole and, to a lesser extent, lansoprazole. Certainly, the studies on these 2 drugs confirm the superior cost effectiveness of PPIs over H2-antagonists in the treatment of reflux oesophagitis and peptic ulceration in both the short and long-terms. Although data are awaited, there is no reason to suggest that this will be any different for pantoprazole and rabeprazole. PPI-based triple therapy for H. pylori eradication appears to be the most cost-effective treatment option for H. pylori-related peptic ulcer disease. It is clear that PPIs are superior in several regards to previously used medications in the treatment of dyspepsia. Which PPI(s) to include in a particular formulary is a more difficult decision. On review of many criteria involved in formulary decisions, differences between the individual PPIs appear minimal. The relative acquisition costs of the PPIs vary nationally and internationally and this may be a critical factor in formulary inclusion decisions. However, one should not ignore non-economic factors, as these should form the basis of any sound drug policies.     

Esomeprazole: a review of its use in the management of gastric acid-related diseases in adults

Esomeprazole (Nexium); S-omeprazole) is a single optical isomer proton-pump inhibitor (PPI) approved for the management of reflux oesophagitis, the symptomatic treatment of gastro-oesophageal reflux disease (GORD), the prevention and healing of NSAID-associated gastric ulcer disease (and the prevention of NSAID-associated duodenal ulcers in the UK), the treatment of Helicobacter pylori infection and associated duodenal ulcer disease (and prevention of relapse of H. pylori-associated peptic ulcers in the UK), and the treatment of Zollinger-Ellison syndrome (and other hypersecretory syndromes in the US).Once-daily oral esomeprazole 40 mg demonstrates greater antisecretory activity than other PPIs. Overall, in well designed clinical studies of 4 weeks' to 6 months' duration in patients with GORD, esomeprazole had similar or better efficacy than other agents. In patients requiring ongoing treatment with NSAIDs, co-therapy with once-daily esomeprazole 20 or 40 mg achieved relief of gastrointestinal symptoms or prevented ulcer occurrence, more effectively than placebo. Esomeprazole was also better than ranitidine 150 mg twice daily in healing NSAID-associated gastric ulcers. In addition, the drug has demonstrated efficacy as part of a triple-therapy regimen for the eradication of H. pylori infection, the healing of H. pylori associated duodenal ulcers and the prevention of relapse of gastric ulcers. Esomeprazole also effectively treated patients with Zollinger-Ellison syndrome. Esomeprazole is generally well tolerated with an adverse-event profile similar to that of other PPIs. Thus, the efficacy and tolerability of esomeprazole for the management of GORD and H. pylori eradication remains undisputed, and the data support its use for the first-line treatment of NSAID-associated gastric ulcer disease and Zollinger-Ellison syndrome.     

Effect of Helicobacter pylori eradication on oesophageal acid exposure in patients with reflux oesophagitis

BACKGROUND: The effect of Helicobacter pylori eradication on reflux oesophagitis is unclear. AIM: To study the effect of H. pylori eradication on oesophageal acid exposure and disease severity in patients with reflux oesophagitis. METHODS: Patients with reflux oesophagitis and H. pylori infection were recruited for 24-h oesophageal pH-metry. They were then randomly assigned to receive either treatment for H. pylori eradication (1-week omeprazole-based triple therapy, followed by 7-week omeprazole) or omeprazole alone (8-week omeprazole). Uninfected patients were recruited as controls. Endoscopy, pH monitoring and symptom assessment were repeated at 26 weeks. RESULTS: Forty patients (25 H. pylori-positive and 15 uninfected) with erosive oesophagitis were studied. Fourteen were randomized to receive treatment for H. pylori eradication and 11 to receive omeprazole alone. There was no difference in the percentage of time the oesophageal pH < 4 before and 26 weeks after treatment among the three groups. However, the percentage of time the oesophageal pH < 2 (P=0.01) and pH < 3 (P=0.02) was significantly increased in patients receiving treatment for H. pylori eradication. Three (21%) patients in the group receiving treatment for H. pylori eradication had worsening of reflux oesophagitis. CONCLUSIONS: H. pylori eradication increases oesophageal acid exposure and may adversely affect the clinical course of reflux disease in a subset of patients.     

Lansoprazole: A Comprehensive Review

Lansoprazole is the second member of the substituted benzimidazole class of antisecretory agents approved for use in the United States. These drugs decrease parietal cell acid secretion by inhibiting H⁺,K⁺-adenosine triphosphatase, the final step in the secretion of acid. Lansoprazole has been studied extensively for the short-term treatment of duodenal and gastric ulcers, reflux esophagitis, and Helicobacter pylori-positive peptic ulcer disease; long-term treatment of Zollinger-Ellison syndrome; and maintenance treatment of erosive esophagitis. A dosage of 30 mg/day produced higher healing rates and equivalent or faster relief of ulcer symptoms than ranitidine or famotidine in patients with duodenal or gastric ulcers and reflux esophagitis. Compared with omeprazole 20 mg/day, that dosage provided faster epigastric pain relief in these patients after 1 week, although healing rates for the two agents were equivalent at 4 and 8 weeks. In patients with peptic ulcer refractory to 8-week therapy with histamine₂-receptor antagonists, healing rates were not significantly different between lansoprazole and omeprazole. In patients with Zollinger-Ellison syndrome, lansoprazole was superior to histamine₂-receptor antagonists and was similar in efficacy, safety, and duration of action to omeprazole. Combinations of lansoprazole or omeprazole with one or two antibiotics produced equivalent eradication of H. pylori. In clinical trials, lansoprazole was well tolerated, with frequency of adverse effects similar to that reported with ranitidine, famotidine, and omeprazole.     

Impact of Helicobacter pylori eradication on heartburn in patients with gastric or duodenal ulcer disease -- results from a randomized trial programme

BACKGROUND: Helicobacter pylori infection has been proposed as a protective factor against the development of gastro-oesophageal reflux disease. AIM: To study heartburn and endoscopic findings before and after H. pylori eradication therapy in patients with peptic ulcer disease. METHODS: In a multicentre trial programme, patients (n = 1497) were randomized to the omeprazole triple therapy group or to the control group, and were followed for 1-6 months after treatment. Patients in whom the infection was eradicated were compared with those in whom infection persisted. The severity of heartburn was measured at baseline and at each return visit. Endoscopy was performed 6 months after therapy in two of the five studies. RESULTS: In patients with duodenal ulcer, there was a significantly lower prevalence of heartburn after successful eradication of H. pylori relative to that after failed eradication (estimated odds ratio, 0.48). The reduction in the prevalence of heartburn in patients with gastric ulcer was independent of the post-treatment H. pylori status. In studies in which ulcer relapse was included in the model, this factor emerged as a significant factor for heartburn. The observed incidence of oesophagitis at the last visit was not influenced by H. pylori status. CONCLUSIONS: Eradication of H. pylori in patients with peptic ulcer disease was associated with a reduced prevalence of heartburn. Prevention of ulcer relapse could be the true cause of this reduction.     

Esomeprazole

Esomeprazole, a new proton pump inhibitor, is the S-isomer of omeprazole and is the first such inhibitor to be developed as a single isomer. Esomeprazole provided better control of intragastric pH than omeprazole, lansoprazole and pantoprazole in trials conducted in patients with gastro-oesophageal reflux disease (GORD) or healthy volunteers (n = 20 to 115). In 2 large randomised, double-blind multicentre trials esomeprazole 20 and/or 40mg for 8 weeks produced higher healing rates of erosive oesophagitis and better symptom control than omeprazole 20 mg in patients with GORD. Esomeprazole 10, 20 or 40mg once daily for 6 months maintained healing versus placebo (p < 0.001) in patients with endoscopically confirmed healed erosive oesophagitis in 2 large randomised, double-blind multicentre trials. Similarly, symptom-driven on-demand use of esomeprazole effectively controlled symptoms of GORD (heartburn) for 6 months in 2 large placebo-controlled trials. Esomeprazole-based triple therapy for 7 days was as effective for eradication of Helicobacter pylori as longer omeprazole-based therapy in 2 randomised double-blind trials including about 450 patients each. Endoscopically confirmed ulcer healing 4 weeks after treatment initiation was reported in about 90% of patients with active duodenal ulcer in both treatment groups. Esomeprazole-based triple therapy for 10 days was more effective than esomeprazole plus clarithromycin for eradication of H. pylori in 233 patients.     

Comparison of ranitidine bismuth citrate plus clarithromycin with omeprazole plus clarithromycin for the eradication of Helicobacter pylori

BACKGROUND: Many dual and triple therapy treatment regimens have been proposed for the eradication of Helicobacter pylori. However, assessing the relative efficacy of these regimens is complicated by differences in study design, and few well-controlled comparative studies have been reported. METHODS: This multicentre, randomized, double-blind study involved 530 duodenal ulcer patients, of whom 520 had confirmed H. pylori infection. Patients received 14 days b.d. dual therapy of either ranitidine bismuth citrate (RBC) 400 mg or omeprazole 20 mg, both with clarithromycin 500 mg to eradicate H. pylori, followed by a further 14 days of treatment with RBC 400 mg b. d. or omeprazole 20 mg o.d. to facilitate ulcer healing. H. pylori eradication and ulcer healing were assessed at least 26 days after the end of treatment. Adverse events were recorded throughout the study. RESULTS: H. pylori was eradicated in 90% of patients who received RBC with clarithromycin and in 66% of patients who received omeprazole with clarithromycin (per protocol; P<0.001). intention-to-treat eradication rates were 77% and 60%, respectively (P<0.001). Ulcer healing rates were 97% in the RBC treatment group and 95% in the omeprazole treatment group. Only 3% and 1% of patients in the RBC and omeprazole treatment groups, respectively, were withdrawn due to adverse events. CONCLUSIONS: RBC with clarithromycin is a simple and highly effective dual therapy regimen for the eradication of H. pylori, and is significantly more effective than omeprazole with clarithromycin. Both treatment regimens are well tolerated and effectively heal duodenal ulcers.     

Esomeprazole: a review of its use in the management of acid-related disorders in the US

Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor to be developed as a single optical isomer. It provides better acid control than current racemic proton pump inhibitors and has a favourable pharmacokinetic profile relative to omeprazole. In large well designed 8-week trials in patients with erosive oesophagitis, esomeprazole recipients achieved significantly higher rates of endoscopically confirmed healed oesophagitis than those receiving omeprazole or lansoprazole. Esomeprazole was effective across all baseline grades of oesophagitis; notably, relative to lansoprazole, as the baseline severity of disease increased, the difference in rates of healed oesophagitis also increased in favour of esomeprazole. In two trials, 94% of patients receiving esomeprazole 40mg once daily achieved healed oesophagitis versus 84 to 87% of omeprazole recipients (20mg once daily). In a study in >5000 patients, respective healed oesophagitis rates with once-daily esomeprazole 40mg or lansoprazole 30mg were 92.6 and 88.8%. Resolution of heartburn was also significantly better with esomeprazole than with these racemic proton pump inhibitors. Long-term (up to 12 months) therapy with esomeprazole effectively maintained healed oesophagitis in these patients. Esomeprazole 20 or 40mg once daily for 4 weeks proved effective in patients with symptomatic gastro-oesophageal reflux disease (GORD) without oesophagitis. Eradicating Helicobacter pylori infection is considered pivotal to successfully managing duodenal ulcer disease. Ten days' triple therapy (esomeprazole 40mg once daily, plus twice-daily amoxicillin 1g and clarithromycin 500mg) eradicated H. pylori in 77 to 78% of patients (intention-to-treat) with endoscopically confirmed duodenal ulcer disease. Esomeprazole is generally well tolerated, both as monotherapy and in combination with antimicrobial agents. The tolerability profile is similar to that of other proton pump inhibitors. Few patients discontinued therapy because of treatment-emergent adverse events (<3% of patients) and very few (<1%) drug-related serious adverse events were reported. CONCLUSIONS: Esomeprazole is an effective and well tolerated treatment for managing GORD and for eradicating H. pylori infection in patients with duodenal ulcer disease. In 8-week double-blind trials, esomeprazole effectively healed oesophagitis and resolved symptoms in patients with endoscopically confirmed erosive oesophagitis. Notably, in large (n >1900 patients) double-blind trials, esomeprazole provided significantly better efficacy than omeprazole or lansoprazole in terms of both healing rates and resolution of symptoms. Long-term therapy with esomeprazole effectively maintained healed oesophagitis in these patients. Esomeprazole was also effective in patients with symptomatic GORD. Thus, esomeprazole has emerged as an effective option for first-line therapy in the management of acid-related disorders.     

Rabeprazole: a review of its use in acid-related gastrointestinal disorders.

Rabeprazole is an inhibitor of the gastric proton pump. It causes dose-dependent inhibition of acid secretion and has a more rapid onset of action than omeprazole. Duodenal ulcers healed faster after treatment with rabeprazole 20 or 40 mg/day than placebo or ranitidine 150 mg 4 times daily and at a generally similar rate to omeprazole 20 mg/day in patients with duodenal ulcers; rabeprazole was similar or superior to these agents in relieving symptoms. Rabeprazole 20 and 40 mg/day healed gastric ulcers faster than placebo, and rabeprazole 20 mg/day healed ulcers at a similar healing rate, to omeprazole 20 mg/day in well controlled 6-week studies. Gastric ulcer symptom relief with rabeprazole was similar or superior to that provided by omeprazole or placebo. In 8-week studies in patients with gastro-oesophageal reflux disease (GERD), rabeprazole 10, 20 and 40 mg/day were more effective than placebo, rabeprazole 20 mg/day was more effective than ranitidine 150 mg twice daily, and rabeprazole 20 mg/day was similar in efficacy to omeprazole 20 mg/day. Symptom relief with rabeprazole in 8-week trials in patients with GERD was superior to that provided by placebo, and similar to ranitidine or omeprazole. Rabeprazole was similar to omeprazole and superior to placebo in both maintenance of healing and prevention of symptoms in patients with healed GERD in 1-year studies. One-week triple therapy with rabeprazole 20 mg twice daily plus 2 antibacterial agents achieved > or = 90% Helicobacter pylori eradication, but, as would be expected, a regimen of rabeprazole 20 mg twice daily plus 1 antibacterial agent was less successful. The drug was as effective as omeprazole and lansoprazole as part of triple therapy for H. pylori eradication. Rabeprazole successfully reduced acid output to target levels and prevented further pathological changes in 10 patients with Zollinger-Ellison syndrome. Usual dosages of rabeprazole are 20 mg/day for 4 weeks to treat duodenal ulcers, 6 weeks for gastric ulcers and 8 weeks for GERD, although some patients with duodenal ulcer may respond to a 10 mg/day dosage. For long term maintenance of GERD healing, 10 or 20 mg daily doses are adequate. Patients with hypersecretory states may need individualised dosages starting at 60 mg/day. The drug was well tolerated in clinical trials, with headache, rash, infection, diarrhoea and flu syndrome as the most common adverse events. In conclusion, rabeprazole appears to be a well tolerated proton pump inhibitor with a rapid onset of action and a low potential for drug interactions. The drug may be used to achieve healing and the relief of symptoms of duodenal ulcer, gastric ulcer and GERD, maintain GERD healing, and can form part of effective regimens to eradicate H. pylori.     

Systematic review: the efficacy of intermittent and on-demand therapy with histamine H2-receptor antagonists or proton pump inhibitors for gastro-oesophageal reflux disease patients

AIM: To perform a systematic review on the efficacy of intermittent and on-demand therapy with either histamine H2-receptor antagonists or proton pump inhibitors for patients with erosive oesophagitis or symptomatic heartburn. METHOD: We conducted randomized-controlled trials of non-continuous therapy in gastro-oesophageal reflux disease patients. RESULTS: Fourteen studies met inclusion criteria. Because of variation in outcome measures statistical pooling of results was not possible. Results were analysed qualitatively. Four studies evaluated intermittent therapy of treatment 3 days a week with omeprazole 20 mg or daily with ranitidine which were not efficacious compared to a daily proton pump inhibitor. Famotidine 10 and 20 mg, ranitidine 75 mg and cimetidine 200 mg were efficacious in five on-demand studies for relief of symptomatic heartburn episodes. In three of four studies, evaluating only non-erosive (endoscopy-negative) gastro-oesophageal reflux disease patients, esomeprazole 20 and 40 mg and omeprazole 10 and 20 mg a day were efficacious using willingness to continue as an endpoint. Lansoprazole 30 mg and omeprazole 20 mg maintained symptom control in 60-70% of healed oesophagitis patients. CONCLUSIONS: Intermittent proton pump inhibitor or H2-receptor antagonist therapy is not effective in maintaining control in oesophagitis patients. H2-receptor antagonists are effective for relief of heartburn episodes. On-demand proton pump inhibitor therapy may work in a proportion of non-erosive gastro-oesophageal reflux disease patients.     

Roxatidine acetate. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic potential in peptic ulcer disease and related disorders.

Roxatidine acetate is a histamine H2-receptor antagonist which, after almost complete oral absorption (greater than 95%), is rapidly converted to its active metabolite, roxatidine, by esterases in the small intestine, plasma and liver. Roxatidine is a potent inhibitor of basal and stimulated gastric acid secretion in animals and humans and, like most other H2-receptor antagonists, has no anti-androgenic effects and does not interfere with the hepatic metabolism of other drugs. Large-scale trials have shown that roxatidine acetate 150mg per day is as effective as standard doses of cimetidine and ranitidine in the treatment of patients with duodenal or gastric ulcer, and that roxatidine acetate 75mg in the evening is likely to become a 'standard' regimen for the prevention of peptic ulcer recurrence. Preliminary data also suggest that roxatidine acetate may be useful in the treatment of reflux oesophagitis and stomal ulcer, and in the prevention of pulmonary acid aspiration. Roxatidine acetate is an H2-receptor antagonist which has been well tolerated in clinical trials. However, broader experience is required before definitive statements about tolerability relative to other H2-receptor antagonists can be made, and before the role of roxatidine acetate in the treatment of reflux oesophagitis and stomal ulcer, and the prophylaxis of acid aspiration pneumonitis, can be clearly defined.     

Is Helicobacter pylori relevant in the management of reflux disease?

Data on the interaction of reflux disease and Helicobacter pylori infection are limited in scope and rigour, controversial and difficult to interpret. Despite this, a framework of understanding is emerging, which is consistent with known effects on gastric acid secretion.
In patients with moderate to severe H. pylori -induced corpus gastritis, eradication can increase substantially impaired gastric acid secretion sufficiently to precipitate reflux disease in people with pre-existing sub-clinical defective gastro-oesophageal competence. By contrast, reflux disease in duodenal ulcer patients probably benefits from eradication of H. pylori . There appears to be no significant impact on reflux disease from eradication in healthy subjects or individuals whose primary problem is reflux disease.
Helicobacter pylori -infected reflux disease patients respond slightly better to proton pump inhibitors. These agents cause a topographic alteration of gastritis from antrum to corpus, the clinical significance of which is controversial.
Many practitioners misjudge the risks and benefits of the effects of H. pylori eradication on reflux disease. Regardless of patient diagnosis, the balance is in favour of H. pylori eradication. For those in whom reflux oesophagitis development is a defined possibility, oesophagitis is mild, easily treated and most unlikely to be associated with any major risk for development of oesophageal adenocarcinoma.