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Letter to the Editor

Editor, – In the article 'Management of acute bleeding in the upper gastrointestinal tract' (Aust Prescr 2005;28:62-6), the authors say that an infusion of a high-dose proton pump inhibitor for 72 hours is recommended and they give the dosing recommendation for omeprazole.1Recently, AstraZeneca has discontinued the intravenous preparation of omeprazole, replacing it with esomeprazole. Consequently, we wish to comment on the choice of proton pump inhibitor now that omeprazole is unavailable.

Almost all clinical trials evaluating continuous infusion in acute gastrointestinal bleeding have used omeprazole. The efficacy of other proton pump inhibitors in equivalent doses is unproven. There are no published trials directly comparing, for example, intravenous omeprazole and pantoprazole for nonvariceal acute upper gastrointestinal bleeding. There is a study of healthy people, uninfected by Helicobacter pylori, which compared intravenous esomeprazole 40 mg with pantoprazole 40 mg once daily. It showed that esomeprazole provides faster and more pronounced control of intragastric acidity.2We are unaware of any published studies on the use of continuous infusion of esomeprazole.

Esomeprazole is the S-enantiomer of omeprazole and has the same pharmacological activity.3The major difference between the enantiomers is in their pharmacokinetics. After equivalent doses, esomeprazole reaches higher plasma concentrations.4The manufacturer has provided unpublished data based on a study in healthy volunteers comparing the effects of various regimens of esomeprazole on maintaining intragastric pH > 4 and pH > 6. The results showed that intravenous esomeprazole 80 mg when given as an initial bolus dose over 30 minutes, followed by a continuous infusion of 8 mg/hr, maintained intragastric pH > 4 and pH > 6 for longer during a 24-hour period than other dosages.

Given the limited data that are available, we are recommending esomeprazole when continuous infusions are necessary, until further evidence becomes available. The dosage for esomeprazole should follow those suggested for continuous infusions of omeprazole, with an initial 80 mg dose given over 30 minutes, followed by continuous infusion of 8 mg/hr (at a concentration of 0.4 mg/mL) over 72 hours.5

Shin Choo
Pharmacist, The Alfred Hospital

Michael Dooley
Professor, Pharmacy Practice, Monash University
Director of Pharmacy, Bayside Health

Stuart Roberts
Gastroenterologist, The Alfred Hospital

Author's comments

Professor R.J. Fraser, one of the authors of the article, comments:

As mentioned in our article, the current standard for pharmacological treatment for non-variceal upper gastrointestinal haemorrhage is intravenous omeprazole or equivalent. Omeprazole has been the proton pump inhibitor studied in the majority of published clinical trials, but a small number have involved other drugs.6Esomeprazole, which will soon replace omeprazole, obviously fulfils the criteria of equivalence, but it is unlikely to be the only drug to do so. Esomeprazole is an enantiomer, with theoretical benefits in terms of metabolism, but to date this has not been shown to provide significant overall benefits compared to racemic preparations.

Many clinicians believe the benefits in gastrointestinal haemorrhage result from a class effect, with the rise in intraluminal pH and resultant clot stability the key to improved outcome. The exact parameters that determine clot stability and the speed with which these need to be attained are unknown. The unpublished data reporting superior acid control in healthy volunteers are likely to have limited relevance to patient therapy. Although drug potency and the speed of acid suppression are clearly important, using these unpublished data to infer benefit in patient management is unjustified. More data are required in patients before making definite recommendations. For economic reasons, and in the absence of comparative randomised clinical trials in patients with gastrointestinal haemorrhage, clinicians frequently prescribe alternatives to omeprazole. Until such trials are done, the selection of proton pump inhibitor will continue to be a balance between cost, potential benefits and ease of administration in the face of incomplete evidence.


  1. Worthley DL, Fraser RJ. Management of acute bleeding in the upper gastrointestinal tract. Aust Prescr 2005;28:62-6.
  2. Wilder-Smith CH, Rohss K, Bondarov P, Hallerback B, Svedberg LE, Ahlbom H. Esomeprazole 40 mg i.v. provides faster and more effective intragastric acid control than pantoprazole 40 mg i.v.: results of a randomized study [published erratum appears in Aliment Pharmacol Ther 2005;21:101]. Aliment Pharmacol Ther 2004;20:1099-104.
  3. Lindberg P, Keeling D, Fryklund J, Andersson T, Lundborg P, Carlsson E. Esomeprazole - enhanced bio-availability, specificity for the proton pump and inhibition of acid secretion [review]. Aliment Pharmacol Ther 2003;17:481-8.
  4. Andersson T, Rohss K, Bredberg E, Hassan-Alin M. Pharmacokinetics and pharmacodynamics of esomeprazole, the S-isomer of omeprazole. Aliment Pharmacol Ther 2001;15:1563-9.
  5. Lau JY, Sung JJ, Lee KK, Yung MY, Wong SK, Wu JC, et al. Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. N Engl J Med 2000;343:310-6.
  6. Leontiadis GI, Sharma VK, Howden CW. Systematic review and meta-analysis of proton pump inhibitor therapy in peptic ulcer bleeding [review]. Br Med J 2005;330:568.