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Nexium |
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Esomeprazole is a proton pump inhibitor (brand names Nexium; Lucen; Esopral and Axagon
in Italy) developed and marketed by AstraZeneca which is used in the
treatment of dyspepsia, peptic ulcer disease (PUD), gastroesophageal
reflux disease (GORD/GERD) and Zollinger-Ellison syndrome. Esomeprazole
is the S-enantiomer of omeprazole (marketed as Losec/Prilosec), and
AstraZeneca claims improved efficacy of this single enantiomer product
over the racemic mixture of omeprazole. However, this greater efficacy
has been disputed, with some claiming it offers no benefit from its
older form. Esomeprazole was the third biggest selling
pharmaceutical drug in the world for 2005, totaling $5.7 billion in
sales. Pharmacology Esomeprazole is a proton pump inhibitor which reduces gastric acid secretion through inhibition of H+/K+-ATPase in gastric parietal cells. By inhibiting the functioning of this enzyme, the drug prevents formation of gastric acid. Clinical use Use in Helicobacter pylori eradication Esomeprazole is combined with the antibiotics clarithromycin and amoxicillin (or metronidazole) in the 7-day eradication triple therapy for Helicobacter pylori. Infection by H. pylori is the causative factor in the majority of peptic and duodenal ulcers. Evidence of efficacy AstraZeneca claims that esomeprazole provides improved efficacy, in terms of stomach acid control, over racemic omeprazole. Many health professionals have expressed the view that this improvement in efficacy is due to the dose of esomeprazole recommended for therapy rather than any superiority of esomeprazole per se. An alternative rationale suggested for the use of esomeprazole was the reduction in interindividual variability in efficacy. However the clinical advantage of this hypothesis has not thoroughly been tested in large-scale trials. Given the large difference in cost between all other proton pump inhibitors and that of Prilosec-OTC (equivalent to omeprazole 20mg), many physicians recommend a trial of over-the-counter products before beginning more extensive therapies and testing. Dosage forms Esomeprazole is available as delayed-release capsules in the United States or as delayed release tablets in Australia and Canada (containing esomeprazole magnesium) in strengths of 20 mg and 40 mg; and as esomeprazole sodium for intravenous injection/infusion. Oral esomeprazole preparations are enteric-coated, due to the rapid degradation of the drug in the acidic conditions of the stomach. This is achieved by formulating capsules using the multiple-unit pellet system. Multiple unit pellet system Esomeprazole capsules are formulated as a "multiple unit pellet system" (MUPS). Essentially, the capsule consists of extremely small enteric-coated granules (pellets) of the esomeprazole formulation inside an outer shell. When the capsule is immersed in an aqueous solution, as happens when the capsule reaches the stomach, water enters the capsule by osmosis. The contents swell from water absorption causing the shell to burst, releasing the enteric-coated granules. For most patients, the multiple-unit pellet system is of no advantage over conventional enteric-coated preparations. Patients for which the formulation is of benefit include those requiring nasogastric tube feeding and those with difficulty swallowing (dysphagia). The granules are manufactured in a fluid bed system with small sugar spheres as the starting material. The sugar spheres are sequentially spray-coated with a suspension containing esomeprazole, a protective layer to prevent degradation of the drug in manufacturing, an enteric coating and an outer layer to reduce granule aggregation. The granules are mixed with other inactive excipients and compressed into tablets. Finally, the tablets are film-coated to improve the stability and appearance of the preparation. Financial impact Between the launch of esomeprazole in 2001 and 2005, the drug has netted AstraZeneca about $14.4 billion. Controversy There has been some controversy about AstraZeneca's behaviour in creating, patenting and marketing of the drug. Critics allege that the drug's successful predecessor Omeprazole is a mixture of two mirror-imaged molecules (esomeprazole and romeprazole), and that the company was trying to "evergreen" its patent by patenting the pure esomeprazole and aggressively marketing to doctors that it is more effective than the mixture, claiming that romeprazole has no beneficial effects on the patient. However, in the acidic environment of the parietal cells both esomeprazole and romeprazole are converted to the same active drug which stops the gastric acid production. |
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