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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 After equivalent doses, esomeprazole reaches higher plasma concentrations.4The manufacturer has provided unpublished data based on a study in healthy volunteers comparing the effects of various regimens of esomeprazole on maintaining intragastric pH 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
Pharmacist, The Alfred Hospital
Professor, Pharmacy Practice, Monash University
Director of Pharmacy, Bayside Health
Gastroenterologist, The Alfred Hospital
- Worthley DL, Fraser RJ. Management of acute bleeding in the upper gastrointestinal tract. Aust Prescr 2005;28:62-6.
- 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.
- 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.
- 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.
- 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.
- 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.