The new proton pump inhibitor esomeprazole (Nexium) will be replacing omeprazole (Prilosec) on the MGH inpatient formulary. Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor (PPI) to be developed that is a single optical isomer. The currently approved uses for PPIs are for the maintenance and healing of erosive esophagitis, symptomatic GERD unresponsive to antacids and/or H₂ antagonist therapy, and the prevention of rebleeding post endoscopic sclerotherapy.

Esomeprazole has the same mechanism of action as omeprazole and the other PPIs. It inhibits the H+/K+-ATPase enzyme. Esomeprazole inhibits basal and stimulated secretion of acid. Following oral doses of esomeprazole, peak plasma levels are usually reached after 1 hour. Bioavailability reaches approximately 90% with repeated doses. Esomeprazole is metabolized by the liver CYP2C19 enzymatic pathway with an elimination half-life of about 1.5 hours. No significant metabolic drug interactions have been reported with phenytoin, diazepam, warfarin or quinidine. The bioavailability of some drugs, such as ketoconazole, iron salts, and digoxin, is negatively affected by acid reduction.

The most common side effects seen with esomeprazole are headache, nausea, vomiting, diarrhea, and abdominal pain. These are the same as those reported with other proton pump inhibitors. The incidence of side effects with esomeprazole is not well documented.

Dosing of esomeprazole^1,2 is as follows:

*used as second-line after H₂-blockers are no longer sufficient.

Data are not available concerning the use of esomeprazole in pregnancy and lactation. The drug has not been studied in pediatrics. Patients with an allergy to any other PPI should not take esomeprazole.

In clinical trials, esomeprazole has been compared only to omeprazole. Therefore data taken from these trials cannot be extrapolated to other PPIs.

Clinical trials show that esomeprazole has superior pharmacokinetics and better suppression of acid secretion than omeprazole. Data show that esomeprazole has been found to have higher plasma concentrations/greater area-under-the-curve (AUCs) and therefore may be more effective at controlling symptoms of gastroesophageal reflux disease (GERD). Studies to date have shown better bioavailability and less variation of effect on acid secretion from patient to patient. One trial compared 20 mg esomeprazole, 40 mg esomeprazole, and 20 mg omeprazole given to 38 patients with GERD once daily for 5 days. Esomeprazole, at either dose, maintained the gastric pH higher and for a longer period of time.¹ These data showed a faster healing of ulcers and fewer recurrences.

Esomeprazole is effective in H. pylori eradication when used in a regimen with antimicrobial agents. The results of three clinical trials showed that once-daily esomeprazole as part of a ten-day regimen of triple therapy with clarithromycin and amoxicillin had similar efficacy rates in eradication of H pylori.³ The results were comparable to those seen with regimens including other PPIs which were given twice daily.

Esomeprazole is effective in healing erosive esophagitis. A clinical trial conducted over 6 months in 318 patients with GERD, who also had erosive esophagitis, healed ulcers in 90% of the patients. Doses of 20 mg and 40 mg of esomeprazole were evaluated in the study. Of the patients treated with esomeprazole, 70% had no recurrence of symptoms at the end of the trial.²

Current data show esomeprazole to be as effective in healing ulcers, and eradicating H pylori as omeprazole. Esomeprazole has superior pharmacokinetic properties and less variability in effectiveness from patient to patient when compared to omeprazole. Esomeprazole shares a similar mechanism of action, side-effect profile, and precautions to currently available proton-pump inhibitors. The better efficacy of esomeprazole may be explained by the fact that it is the active single isomer of omeprazole, which is a racemic mixture. Based on the clinical and economic data available, MGH will be exclusively using esomeprazole over other proton pump inhibitors such as omeprazole.

Outpatient prescribing of PPIs should be based on clinical and economic data as well. Economic data can be found in the patient's insurance plan formulary. Average wholesale prices of all PPIs are included as a reference.

References:

1. Lind T, Rydberg L, Kyleback A, et al. Esomeprazole provides improved acid control vs. omeprazole in patients with symptoms of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2000;14:861-867.

2. Johnson DA, Benjamin SB, Vakil NB, et al. Esomeprazole once daily for 6 months is effective therapy for maintaining healed erosive esophagitis and for controlling gastroesophageal reflux disease symptoms: a randomized, double-blind, placebo-controlled study of efficacy and safety. Am J Gastroenterol 2001;96:27-34.

3. Laine L, Fennerty B, Osato M, et al. Esomeprazole-based Helicobacter pylori eradication therapy and the effect of antibiotic resistance: results of three US multicenter, double-blind trials. Am J Gastroenterol 2000;95:3393-3398.