Esomeprazole magnesium is used for short-term (4-8 weeks) treatment of diagnostically confirmed erosive esophagitis in patients with gastroesophageal reflux disease (GERD). The drug also is used as maintenance therapy following healing of erosive esophagitis to reduce recurrence of the disease. In addition, esomeprazole is used for short-term (4-8 weeks) treatment of symptoms (e.g., heartburn) of GERD in patients without erosive esophagitis. In infants, esomeprazole is used for short-term (up to 6 weeks) treatment of erosive esophagitis due to acid-mediated GERD. Potential benefits of proton-pump inhibitors in gastroesophageal reflux and esophagitis are thought to result principally from reduced acidity of gastric contents induced by the drugs and resultant reduced irritation of esophageal mucosa; the drugs can effectively relieve symptoms of esophagitis (e.g., heartburn) and promote healing of ulcerative and erosive lesions. Because esomeprazole (S-omeprazole) is not eliminated as rapidly as R-omeprazole, more drug reaches and blocks the proton pump, providing greater control of intragastric pH than racemic omeprazole.
Suppression of gastric acid secretion is considered by the American College of Gastroenterology (ACG) to be the mainstay of treatment for GERD, and a proton-pump inhibitor or histamine H2-receptor antagonist is used to achieve acid suppression, control symptoms, and prevent complications of the disease. Because GERD is considered to be a chronic disease, the ACG states that many patients with GERD will require long-term, even lifelong, treatment. The ACG states that proton-pump inhibitors are more effective (i.e., provide more frequent and more rapid symptomatic relief and healing of esophagitis) than histamine H2-receptor antagonists for treatment of GERD, and are effective and appropriate as maintenance therapy in many patients with the disease. Proton-pump inhibitors also provide greater control of acid reflux than do prokinetic agents (e.g., cisapride [no longer commercially available in the US], metoclopramide) without the risk of severe adverse effects associated with these agents.
Efficacy of esomeprazole in the treatment of endoscopically diagnosed erosive esophagitis was established in 4 controlled studies in patients receiving esomeprazole 20 or 40 mg daily or omeprazole 20 mg daily for 8 weeks. Rates of healing and sustained resolution of heartburn achieved with esomeprazole were similar to or exceeded those achieved with omeprazole.
Efficacy in the long-term maintenance of healing was established in 2 controlled studies in patients with endoscopically confirmed healing of erosive esophagitis receiving esomeprazole 10, 20, or 40 mg daily or placebo for 6 months. Patients receiving esomeprazole remained in remission longer and experienced fewer recurrences than patients receiving placebo; although esomeprazole 10 mg daily provided less benefit than esomeprazole 20 or 40 mg daily, no additional benefit of the 40-mg daily dosage over the 20-mg daily dosage was reported.
Efficacy in patients with symptomatic GERD was established in 2 controlled studies in patients with a 6-month or longer history of heartburn episodes, no endoscopic evidence of erosive esophagitis, and heartburn for at least 4 of the 7 days immediately prior to randomization; patients received esomeprazole 20 or 40 mg daily or placebo for 4 weeks. The percentage of patients who were symptom-free was substantially higher in the group receiving esomeprazole than in the group receiving placebo; no additional benefit of the 40-mg dosage over the 20-mg dosage was reported.
In patients with erosive esophagitis who are unable to take esomeprazole orally, esomeprazole sodium may be used IV for short-term treatment of GERD. In several open-label crossover studies in patients with symptoms of GERD with or without erosive esophagitis, IV administration of esomeprazole 20 or 40 mg as either a 3-minute injection or a 15-minute infusion once daily for 10 days inhibited gastric acid secretion to a similar extent as the corresponding (20 or 40 mg) oral dosage of the drug.
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Esomeprazole magnesium is used in combination with amoxicillin and clarithromycin (triple therapy) for short-term (10 days) treatment of patients with H. pylori infection and duodenal ulcer disease (active duodenal ulcer or a history of duodenal ulcer within the preceding 5 years).
Efficacy of esomeprazole-based triple therapy for H. pylori eradication was established in 2 controlled studies in patients with documented H. pylori infection and at least one endoscopically verified duodenal ulcer (or documented history of duodenal ulcer disease in the preceding 5 years). At 4 weeks after treatment, H. pylori eradication rates were substantially higher in patients receiving triple therapy (esomeprazole 40 mg once daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily) for 10 days than in those receiving dual therapy (esomeprazole 40 mg daily and clarithromycin 500 mg twice daily) or monotherapy with esomeprazole 40 mg daily for 10 days.
Prevention of Nonsteroidal Anti-inflammatory Agent-induced Ulcers
Esomeprazole magnesium is used for reducing the occurrence of gastric ulcers associated with chronic nonsteroidal anti-inflammatory agent (NSAIA) therapy in patients at risk for developing these ulcers, including individuals 60 years of age or older and/or those with a documented history of gastric ulcers. Efficacy for this indication was established in two 6-month randomized, controlled studies in patients receiving chronic therapy with either a prototypical NSAIA or a selective cyclooxygenase-2 (COX-2) inhibitor; individuals enrolled in these studies were considered to be at risk for developing NSAIA-associated ulcers because of their age (60 years or older) and/or a history of documented gastric or duodenal ulcer within the previous 5 years, but they had no evidence of gastric or duodenal ulcers on endoscopic examination at the start of the studies. Results of the studies indicated that esomeprazole 20 or 40 mg daily was more effective than placebo in preventing gastric ulcer occurrence during 6 months of treatment; however, no additional benefit was observed with the 40-mg daily dosage compared with the 20-mg daily dosage. In these studies, 94.7-95.4% of patients receiving esomeprazole 20 mg daily, 95.3-96.7% of those receiving esomeprazole 40 mg daily, and 83.3-88.2% of those receiving placebo remained free of gastric ulcers, as determined by serial endoscopic examinations, throughout the 6-month study. The occurrence rate of duodenal ulcers was too low to determine the effect of esomeprazole therapy on duodenal ulcer occurrence.
In 2 other randomized studies, combined therapy with esomeprazole and naproxen was associated with a lower cumulative incidence of gastric ulcer compared with naproxen therapy alone over 6 months of treatment (4.1-7.1 versus 23.1-24.3%). Patients in these studies were randomized to receive either esomeprazole in fixed combination with naproxen (as immediate-release esomeprazole 20 mg and delayed-release naproxen 500 mg twice daily) or delayed-release naproxen (500 mg twice daily) alone. In both studies, patients receiving combined therapy with esomeprazole and naproxen were less likely than patients receiving naproxen alone to discontinue therapy because of adverse upper GI effects, including duodenal ulcers (4 versus 12%). Most patients (83%) in these studies were 50-69 years of age; those younger than 50 years of age were required to have a history of documented gastric or duodenal ulcer within the previous 5 years. About one-fourth of patients also received low-dose aspirin. Efficacy in patients receiving concomitant aspirin therapy was similar to that in the overall study population.
Pathologic GI Hypersecretory Conditions
Esomeprazole magnesium is used for the long-term treatment of pathologic GI hypersecretory conditions. Efficacy for this indication was established in an open-label study in a limited number of patients with previously diagnosed pathologic GI hypersecretory conditions (e.g., Zollinger-Ellison syndrome, idiopathic gastric acid hypersecretion); patients received total daily dosages of esomeprazole ranging from 80 mg-240 mg. The drug generally was well tolerated at these dosages for the duration of the study (12 months). At 12 months of therapy, 90% of patients treated with esomeprazole had controlled basal acid output (BAO) levels, defined as BAO of less than 5 or 10 mEq/hour in patients who had or had not previously undergone gastric acid-reducing surgery, respectively.
Crohn's Disease-associated Ulcers
Although evidence currently is limited, proton-pump inhibitors have been used for gastric acid-suppressive therapy as an adjunct in the symptomatic treatment of upper GI Crohn's disease, including esophageal, gastroduodenal, and jejunoileal disease. Most evidence of efficacy to date has been from case studies in patients with Crohn's-associated peptic ulcer disease unresponsive to other therapies (e.g., H2-receptor antagonists, cytoprotective agents, antacids, and/or sucralfate).
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