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Aprotinin is indicated for prophylactic use to reduce blood loss and blood transfusion in adult patients at high risk of major blood loss undergoing isolated cardiopulmonary bypass graft surgery (CABG).¹

Aprotinin has demonstrated reduced incidence of massive post-operative bleeding and reduced need for transfusion of blood products for patients undergoing isolated coronary artery bypass graft surgery.² Additionally, aprotinin has been shown to be superior to both TXA and EACA with respect to avoiding re-operation for bleeding and significant peri-operative bleeding from chest tubes in CABG surgery.²

A.

Aprotinin is indicated for prophylactic use to reduce blood loss and blood transfusion in adult patients at high risk of major blood loss undergoing isolated cardiopulmonary bypass graft surgery (CABG).¹ 

The decision to use aprotinin would be based on a patient assessment made by the cardiothoracic surgeon and/or anaesthetist. Patients who are undergoing isolated coronary artery bypass graft surgery (on pump) and who are considered at high risk of major blood loss and transfusion may benefit from receiving aprotinin.

Please refer to the section on our website: Which patients undergoing isolated CABG are at higher risk of transfusion?

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Aprotinin is indicated for prophylactic use to reduce blood loss and blood transfusion in adult patients at high risk of major blood loss undergoing isolated cardiopulmonary bypass graft surgery (CABG).

Aprotinin is contraindicated in the following patients:

• Those who are hypersensitive to the active substance.
• Those with a positive aprotinin-specific IgG antibody test.
• Those with a suspected previous exposure including in fibrin sealant products during the last 12 months (if no aprotinin specific IgG antibody test is possible prior to treatment).

Aprotinin should also not be used when CABG surgery is combined with another cardiovascular surgery because the benefit risk balance of aprotinin in other cardiovascular procedures has not been established.

A.

Aprotinin is indicated for prophylactic use to reduce blood loss and blood transfusion in adult patients at high risk of major blood loss undergoing isolated cardiopulmonary bypass graft surgery (CABG). ¹

Aprotinin has a well-established safety profile based on decades of research. A meta-analysis demonstrated no increase in the risk of in-hospital mortality for patients treated with aprotinin vs. placebo or other antifibrinolytic agents.²

These findings are in line with other leading reviews of aprotinin:

– Cochrane review (2011) – which also showed no increased risk of myocardial infarction, stroke or renal dysfunction/failure vs. placebo³

– Health Canada guidance (2011) – which concluded the benefit of aprotinin outweighs its risk in appropriate patients⁴

– European regulatory assessment (2013) – which recommended lifting the licence suspension ⁵

Additionally, The EACTS/EACTA 2017 Guidelines recommend using aprotinin: Antifibrinolytic therapy (TXA, aprotinin and EACA) is recommended to reduce bleeding and transfusions of blood products and reoperations for bleeding (TXA and aprotinin).⁶

Adverse drug reactions (ADRs) based on all placebo-controlled clinical studies with aprotinin sorted by CIOMS III categories of frequency (aprotinin n=3817 and placebo n=2682; status: April 2005) are listed as follows:¹

If you have any concerns over the safety of aprotinin please use our contact form to make an enquiry to our team who would be happy to discuss any particular concerns you may have. Alternatively, if you have an adverse event you wish to report please contact Nordic Pharma Ltd. on 0800 121 8924 or email at [email protected]. Adverse events can also be reported by using the reporting forms and information found at www.yellowcard.mhra.gov.uk or search for MHRA Yellow Card in the Google Play or Apple App Store.

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Results from recent observational studies indicate that renal dysfunction could be triggered by aprotinin, particularly in patients with pre-existing renal dysfunction. An analysis of all pooled placebo-controlled studies in patients undergoing coronary artery bypass graft (CABG) has found elevations of serum creatinine values >0.5 mg/dL above baseline in patients with aprotinin therapy. Careful consideration of the balance of risks and benefits is therefore advised before administration of aprotinin to patients with pre-existing impaired renal function or those with risk factors (such as concomitant treatment with aminoglycosides).¹

An increase in renal failure and mortality compared to age-matched historical controls has been reported for aprotinin treated patients undergoing cardiopulmonary bypass with deep hypothermic circulatory arrest during operation of the thoracic aorta. Adequate anticoagulation with heparin must be assured (see also above).

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In a study of patients at high risk of bleeding and transfusion, aprotinin offered the following advantages over TXA:

• Lower post-operative blood loss
• Lower need for transfusions
  • 32% aprotinin vs 46% TXA
• Shorter stays in ICU (61 hours [24-72h] for aprotinin vs. 87 hours [48-96h] for TXA; p<0.001)

In this study, patients in the TXA group received an intravenous bolus infusion of 10 to 30mgkg^_1 for 10 to 20 min as a loading dose after induction of anaesthesia. Subsequently, a continuous intravenous infusion ranging from 0.5 to 15mgkg^_1 h^_1, depending on the centre and the patient’s renal function, was administered until the end of surgery. This is outside the indicated dosing for TXA in the UK SPC.

For further information on how the mode of action of aprotinin differs from that of TXA please refer to our section About aprotinin.

A.

In the SmPCs of both aprotinin and tranexamic acid, there is no mention of possible pharmacological interactions between these two products. However, Nordic Pharma Ltd. does not recommend combining different antifibrinolytics during a surgical procedure.

Please refer to our section About aprotinin for further information regarding the differences between aprotinin and TXA.

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Owing to the risk of allergic/anaphylactic reactions, a 1 ml (10,000 KIU) test dose should be administered to all patients at least 10 minutes prior to the remainder of the dose. After the uneventful administration of the 1 ml test dose, the therapeutic dose may be given. A H1-antagonist and a H2-antagonist may be administered 15 minutes prior to the test dose of aprotinin. In any case, standard emergency treatments for anaphylactic and allergic reactions should be readily available.

A.

The safety and efficacy in children below 18 years of age have not been established. Therefore, aprotinin should not be used in children.

The indication of aprotinin is prophylactic use to reduce blood loss and blood transfusion in adult patients who are at high risk of major blood loss undergoing isolated cardiopulmonary bypass graft surgery (i.e. CABG that is not combined with other cardiovascular surgery).

A.

Aprotinin is indicated for prophylactic use to reduce blood loss and blood transfusion in adult patients at high risk of major blood loss undergoing isolated cardiopulmonary bypass graft surgery. Aprotinin should only be used after careful consideration of the benefits and risks, and alternative treatments.

Nordic Pharma Ltd. are therefore unable to supply any centre which does not perform cardiac surgery.

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Aprotinin is available for cardiac centres to purchase from HealthNet Homecare. If you have previously not ordered aprotinin, you will be asked to supply further information before your order will be processed.

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The price of aprotinin is £83 per vial. Please see aprotinin Prescribing Information for more information