Proton Pump Inhibitors in the Management of Patients with Acid-Peptic Disorders: A Managed Care Perspective

INTRODUCTION Acid-peptic disorders comprise conditions whose pathogenesis involves the effects of gastric acid and peptic activity on the tissue, although other factors may also contribute to the condition.1 Included among these disorders are gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), gastroduodenal injury and resultant bleeding caused by medications (e.g., aspirin and other nonsteroidal antiinflammatory drugs [NSAIDs]), and such acid-hypersecretory conditions as Zollinger–Ellison syndrome. With an estimated prevalence of 25% to 35% in the general population, acid-peptic disorders are among the most common conditions diagnosed and treated by primary care physicians, internists, and gastroenterologists.2 Rheumatologists, orthopedic surgeons, otolaryngologists, surgeons, and intensivists are also major prescribers of these drugs for preventing and treating acid-peptic disorders. The medical impact of these disorders and their treatment is substantial, as is their effect on patients’ quality of life. In addition, their burden on society is enormous. Indeed, it is estimated that acid-peptic disorders account for more than $20 billion in health care expenditures in the U.S. annually.2 The pathophysiology of acid-peptic disorders involves an imbalance between the secretion of acid (and pepsin) and the mucosal defenses of the exposed tissue. Treatment is centered on correcting this imbalance and is detailed in numerous guidelines. For decades, the primary means of therapy was to neutralize gastric acid with antacids. The advent of cimetidine (Tagamet®, GlaxoSmithKline), the first marketed histamine-2 receptor antagonist (H2RA), in 1977 represented an important advance in the management of patients with acidpeptic disorders, achieving the reduction of gastric acid secretion while avoiding the inconvenience of large, multiple daily doses of antacids. Today, proton pump inhibitors (PPIs) have largely supplanted the H2RAs. Compared with H2RAs, PPIs are more effective suppressors of gastric acid secretion. Moreover, they can be administered once daily in many patients, they are well tolerated, and they are not associated with the development of pharmacological tolerance or refractoriness. Omeprazole (Prilosec®, AstraZeneca), the first drug of this class, was approved by the FDA in 1989, followed by lansoprazole (Prevacid®, TAP) in 1995, rabeprazole (Aciphex®, Janssen/Esai) in 1999, pantoprazole (Protonix®, Wyeth) in 2000, and esomeprazole magnesium (Nexium®, AstraZeneca) in 2001.3 The indications approved for these agents vary, but they include the most prevalent and clinically important acidpeptic disorders (Table 1). This article summarizes the pertinent data on the efficacy and safety of PPIs in the treatment of acid-peptic disorders and describes important considerations in selecting among these agents and between intravenous (IV) and oral preparations.