Information about Esomeprazole
Omeprazole and esomeprazole are proton pump inhibitors (PPIs) and potent inhibitor of gastric acidity which are widely used in the therapy of gastroesophageal reflux and peptic ulcer disease. Omeprazole and esomeprazole therapy are both associated with a low rate of transient and asymptomatic serum aminotransferase elevations and are rare causes of clinically apparent liver injury.
Mechanism of action of Esomeprazole
Esomeprazole (es" oh mep' ra zole) is the S-isomer of omeprazole and exhibits delayed clearance and thus higher potency on a molar basis than omeprazole, which is a racemic mixture of both S- and R-isomers. The pharmacokinetics, mechanism of action and clinical efficacy of esomeprazole is quite similar to that of omeprazole. Esomeprazole was approved for use in the United States in 2001 with similar indications as omeprazole includig peptic ulcer disease, gastroesophageal reflux disease and prevention of stress ulcers. Esomeprazole is also available in multiple forms and typically used in 20 mg delayed release capsules generically and under the brand name Nexium. On a molar basis, esomeprazole is more potent than omeprazole and the recommended dose in adults is 20 mg once daily, with twice daily doses for more severe cases of gastrointestinal reflux and peptic ulcer disease, and doses of up to 60 mg daily for Zollinger-Ellison syndrome. Combinations of esomeprazole with antibiotics for 10 to 14 days are effective and recommended for eradication of H. pylori infection. Both omeprazole and esomeprazole are very well tolerated and both are now available without prescription in multiple over-the-counter forms.
Side effects of Esomeprazole
Side effects of omeprazole and esomeprazole are uncommon and usually mild; they include diarrhea, nausea, vomiting, abdominal discomfort, flatulence, skin rash, headaches and dizziness. Severe side effects are rare but can include hypersensitivity reactions. Long-term use of rabeprazole may be associated with bone fractures, acute interstitial nephritis, lupus erythematosus, vitamin B12 deficiency and hypomagnesemia.
Liver safety of Esomeprazole
Despite their wide use, omeprazole and esomeprazole have only rarely been associated with hepatic injury. In large scale, long term trials , serum ALT elevations occurred in less than 1% of patients and at rates similar to those that occurred with placebo or comparator drugs. A small number of cases of clinically apparent liver disease due to omeprazole or esomeprazole have been published, the frequency of these cases probably being less than 1:100,000 users. A somewhat characteristic clinical phenotype has been described, with most cases arising during the first 1 to 4 weeks of therapy and being marked by an acute hepatocellular pattern of injury, with rapid recovery upon withdrawal. Rash, fever and eosinophilia were rare, as is autoantibody formation. Liver biopsy typically shows prominent centrolobular necrosis, suggestive of an acute, toxic hepatic injury (acute hepatic necrosis); however, recurrence upon rechallenge has been documented in several cases. In some instances, other organ involvement is prominent including rhabdomyolysis, lactic acidosis, renal insufficiency or Stevens Johnson syndrome. In large case series of drug induced liver injury, omeprazole and esomeprazole have accounted for few instances of symptomatic acute liver injury and rare instances of acute liver failure.
The antiulcer agents in clinical use