Medicines Q&As
Q&A 41.7
How should continuous infusions of branded proton pump
inhibitors be given for acute upper gastrointestinal bleeding?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Before using this Q&A, read the disclaimer at www.ukmi.nhs.uk/activities/medicinesQAs/default.asp
Date prepared: 18th September 2012
Background
Acute upper gastrointestinal bleeding is associated with significant morbidity and mortality. In high-risk
patients, once the initial episode of bleeding has been controlled by endoscopic therapy, the goal is to
prevent rebleeding and associated complications. The rebleeding rate after initial endoscopic
haemostasis of upper gastrointestinal ulcers may be as high as 10% to 25% (1).
Acid and pepsin impair the haemostatic process of ulcers and non-variceal upper gastrointestinal
lesions (1). It has been suggested that increasing and maintaining intragastric pH to ≥ 6.0 may
decrease the risk of rebleeding by increasing clot stability (2).
Intravenous proton pump inhibitors (PPIs) have been shown to provide potent and long lasting acid
suppression, without the development of tolerance (1).
Answer
In the UK, intravenous formulations of omeprazole, pantoprazole and esomeprazole are currently
available (3). Omeprazole and pantoprazole are not licensed to be given by continuous infusion (4,5).
Intravenous esomeprazole is licensed for the prevention of rebleeding following therapeutic
endoscopy for acute bleeding gastric or duodenal ulcers (6).
Dose
The National Institute for Health and Clinical Excellence (NICE) recommends that proton pump
inhibitors should be offered to patients with non-variceal upper gastrointestinal bleeding and stigmata
of recent haemorrhage shown at endoscopy (7). However, the route of administration and dosage are
not specified.
Current guidance from the Scottish Intercollegiate Guidelines Network (SIGN) recommends that
“high-dose intravenous PPI therapy (e.g. omeprazole or pantoprazole 80mg bolus followed by
8mg/hour infusion for 72 hours) should be used in patients with major peptic ulcer bleeding (active
bleeding or non-bleeding visible vessel) following endoscopic haemostatic therapy” (8). The British
Society of Gastroenterology states that it has decided to commend the SIGN document and adopt it
as a standard of care (9). International Consensus Recommendations advise the same regimen to
decrease rebleeding and mortality in patients with high-risk stigmata who have undergone successful
endoscopic therapy (10).
Administration
The administration details and stability data given below refer to the branded products stated.
Omeprazole is available as Losec® intravenous infusion and Losec IV injection, both as 40mg vials.
The two preparations have different excipients and due to a lack of stability data the injection is not
interchangeable with the infusion. Losec IV injection must be given only as an intravenous injection
and it must not be added to infusion solutions (11). To avoid confusing the two varieties of the same
injectable, the Losec® intravenous infusion preparation should be used for this indication.
From the NHS Evidence website www.evidence.nhs.uk
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Medicines Q&As
The exact administration details for the initial IV omeprazole 80mg dose followed by an 8mg/hour
infusion are not always stated in the published clinical trials. However, the omeprazole monograph in
the BNF states that omeprazole should be given as an initial intravenous infusion of 80mg over 40–60
minutes (3). After the initial 80mg dose has been given, one 40mg intravenous infusion vial should be
reconstituted with approximately 5ml of sodium chloride 0.9% or glucose 5%, immediately diluted to
100ml using the same infusion fluid (4) and then administered at a rate of 8mg/hour (3), i.e. over 5
hours. This can then be repeated with a new vial each time until the 72 hour period is completed. The
manufacturer has information to show that the product is chemically and physically stable in sodium
chloride 0.9% for 12 hours and in glucose 5% for 6 hours at 25ºC (4), and a published study shows
chemical stability in both infusion fluids for up to 48 hours (at 22 ºC) (12). Despite this the vial does not
contain a preservative and the manufacturer advises from a microbiological point of view that the
reconstituted solution should be used immediately unless it has been reconstituted under controlled
and validated aseptic conditions (4).
Pantoprazole is available as Protium ® injection in a 40mg vial. Again, an 80mg IV dose is given
initially, followed by a continuous infusion. For infusion one vial should be reconstituted with 10ml
sodium chloride 0.9% and then further diluted with 100ml sodium chloride 0.9% or glucose 5%. The
SPC states that the reconstituted solution is chemically and physically stable for 12 hours at 25ºC (5),
yet a published study again shows chemical stability for up to 48 hours (at 22 ºC) (12). However, note
that the SPC also states that, from a microbiological point of view, the reconstituted product should be
used immediately. If not, in-use storage times and conditions are the responsibility of the user (5).
In a pilot study, each 40mg pantoprazole vial was reconstituted with 10ml sodium chloride 0.9% and
an initial bolus injection of 80mg (two reconstituted vials, total 20ml) was given intravenously over 2
minutes. Following this initial dose, three reconstituted vials of 40mg pantoprazole in 30ml sodium
chloride 0.9% was infused, protected from direct light, at a constant rate of 8mg/hour and a fresh
solution prepared every 12 hours until the end of the infusion (72 hours) (13). No stability data were
given and this concentration of pantoprazole infusion is not licensed by the manufacturer.
Esomeprazole is available as Nexium ® IV 40mg powder for solution for injection/infusion. Following
therapeutic endoscopy, 80mg should be administered intravenously over 30 minutes, followed by a
continuous intravenous infusion of 8mg/hour given over 71.5 hours (total infusion time is therefore 72
hours). A solution for infusion of 80mg is prepared by dissolving the contents of two vials of
esomeprazole 40mg in up to 100ml of 0.9% sodium chloride for intravenous use. After reconstitution,
chemical and physical in-use stability has been demonstrated for 12 hours at 30°C. From a
microbiological point of view, the product should be used immediately (6).
Summary



Current guidance recommends that high-dose intravenous PPI therapy (80mg bolus followed by
8mg/hour infusion for 72 hours) should be used in patients with major peptic ulcer bleeding
following endoscopic haemostatic therapy (8,9,10).
Omeprazole and pantoprazole are not licensed to be given by continuous intravenous infusion
(4,5) and use in this way is therefore the responsibility of the prescribing physician. Intravenous
esomeprazole is licensed for the prevention of rebleeding following therapeutic endoscopy for
acute bleeding gastric or duodenal ulcers (6).
After administration of the initial 80mg dose, the continuous infusion can be prepared by
reconstituting a 40mg vial of either omeprazole (Losec ® infusion) or pantoprazole (Protium®) and
further diluting in 100ml of sodium chloride 0.9% or glucose 5%. This can be given at a rate of
8mg/hour (i.e. over 5 hours), and repeated with a fresh vial after that time. Depending on the host
organisation’s attitude to microbiological stability, infusions could be made up and run over 24-48
hours if necessary since omeprazole (Losec®) and pantoprazole (Protium®) at a concentration of
400 microgram/ml are chemically stable in sodium chloride 0.9% or glucose 5% for this period
(12).
From the NHS Evidence website www.evidence.nhs.uk
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Medicines Q&As

After administration of the initial intravenous dose of 80mg esomeprazole, the contents of two
40mg vials of esomeprazole are dissolved in up to 100ml of 0.9% sodium chloride and given at a
rate of 8mg/hour (i.e. over 10 hours). This is repeated with fresh vials after that time (6).
Limitations
 This Q&A has concentrated on the technical details of how intravenous PPIs are given and not
the evidence to support their use and effective dose for the indications described, their relative
efficacy, nor their safety profiles.
 The administration details and stability data included in this Q&A refer to the branded products
stated.
 Cost-effectiveness studies, the use of IV PPIs prior to endoscopy and studies in children have not
been considered.
 Only the use of IV PPIs for the management of non-variceal upper gastrointestinal bleeding has
been addressed.
References
(1) Kovacs TOG, Jensen DM. The short-term medical management of non-variceal upper
gastrointestinal bleeding. Drugs 2008;68(15):2105-2111.
(2) Bardou M, Martin J, Barkun A. Intravenous proton pump inhibitors. An evidence-based review of
their use in gastrointestinal disorders. Drugs 2009;69(4):435-448.
(3) Joint Formulary Committee. British National Formulary. No 64. September 2012. London: BMJ
Group and Pharmaceutical Press. Electronic edition. Accessed via http://www.bnf.org/ on 24th
September 2012.
(4) Summary of Product Characteristics. Losec Infusion 40mg (omeprazole). AstraZeneca UK Ltd.
Accessed via http://www.medicines.org.uk/emc/ on 20th September 2012. SPC last updated on
the eMC on 5th September 2012.
(5) Summary of Product Characteristics. Protium 40mg i.v. Powder for Solution for Injection
(pantoprazole). Nycomed UK Ltd. Accessed via http://www.medicines.org.uk/emc/ on 20th
September 2012. SPC last updated on the eMC on 25th January 2012.
(6) Summary of Product Characteristics. Nexium I.V. 40mg Powder for solution for injection/infusion
(esomeprazole). AstraZeneca UK Ltd. Accessed via http://www.medicines.org.uk/emc/ on 20th
September 2012. SPC last updated on the eMC on 4th July 2012.
(7) National Institute for Health and Clinical Excellence. Acute upper gastrointestinal bleeding:
management. NICE Clinical Guideline 141. June 2012. Accessed via
http://www.nice.org.uk/nicemedia/live/13762/59549/59549.pdf on 20th September 2012.
(8) Scottish Intercollegiate Guidelines Network (SIGN). Management of acute upper and lower
gastrointestinal bleeding A national clinical guideline. SIGN Guideline 105. September 2008.
Accessed via http://www.sign.ac.uk/pdf/sign105.pdf on 24th September 2012.
(9) British Society of Gastroenterology. Accessed via http://www.bsg.org.uk/clinicalguidelines/endoscopy/guidelines-for-non-variceal-upper-gastrointestinal-haemorrhage.html on
24th September 2012.
(10) Barkun AN, Bardou M, Kuipers EJ et al for the International Consensus Upper Gastrointestinal
Bleeding Conference Group. International consensus recommendations on the management of
patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med 2010;152:101-113.
(11) Summary of Product Characteristics. Losec I.V. Injection 40mg (omeprazole). AstraZeneca UK
Ltd. Accessed via http://www.medicines.org.uk/emc/ on 20th September 2012. SPC last updated
on the eMC on 6th September 2012.
(12) Carpenter JF, McNulty MA, Dusci LJ et al. Stability of omeprazole sodium and pantoprazole
sodium diluted for intravenous infusion. Journal of Pharmaceutical Technology 2006;22:95-98.
(13) Van Rensburg CJ, Hartmann M, Thorpe A et al. Intragastric pH during continuous infusion with
pantoprazole in patients with bleeding peptic ulcer. Am J Gastroenterol 2003;98(12):2635-2641.
From the NHS Evidence website www.evidence.nhs.uk
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Medicines Q&As
Quality Assurance
Prepared by
Kate Pickett (based on earlier work by Louisa Rowlands and Sandra Hicks), Medicines Q&A
Pharmacist, Wessex Drug and Medicines Information Centre, University Hospital Southampton NHS
Foundation Trust.
Date Prepared
18th September 2012
Checked by
Sue Gough, Critical Evaluation Pharmacist, Wessex Drug and Medicines Information Centre,
University Hospital Southampton NHS Foundation Trust.
Date of check
17th October 2012
Search strategy
Medline via NHS Evidence: [exp INFUSIONS, PARENTERAL/ OR exp INFUSIONS,
INTRAVENOUS/] AND [exp OMEPRAZOLE/ OR pantoprazole.af OR esomeprazole.af]. Limits: H=Y
and LG=EN since 01/01/2000.
Embase via NHS Evidence: exp CONTINUOUS INFUSION/ AND exp PROTON PUMP INHIBITOR/.
Limits: H=Y and LG=EN.
Electronic Medicines Compendium accessed via www.medicines.org.uk/emc
NICE website accessed via www.nice.org.ukSIGN website accessed via www.sign.ac.uk
NHS Evidence accessed via http://www.evidence.nhs.uk/
Cochrane Library accessed via http://www.thecochranelibrary.com/view/0/index.html
British Society of Gastroenterology website accessed via www.bsg.org.uk
BNF No 64 September 2012 accessed via www.bnf.org
From the NHS Evidence website www.evidence.nhs.uk
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