NAME OF THE MEDICINAL PRODUCT: Aprotinin 10,000 KIU/ML Injection BP. PRESENTATION: Each 50ml 1 vial of 50 mL contains aprotinin concentrated solution, corresponding to 500,000 KIU (Kallikrein Inhibitor Units) in sterile 0.9% sodium chloride solution. INDICATIONS: Aprotinin is indicated for 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. coronary artery bypass graft surgery that is not combined with other cardiovascular surgery). Aprotinin should only be used after careful consideration of the benefits and risks, and the consideration that alternative treatments are available. POSOLOGY AND METHOD OF ADMINISTRATION: Posology: An appropriate aprotinin-specific IgG antibody test may be considered before administration of aprotinin. Adult: 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 (see section 4.4). A loading dose of 1 - 2 million KIU is administered as a slow intravenous injection or infusion over 20 - 30 minutes after induction of anaesthesia and prior to sternotomy. A further 1 - 2 million KIU should be added to the pump prime of the heart-lung machine. To avoid physical incompatibility of aprotinin and heparin when adding to the pump prime solution, each agent must be added during recirculation of the pump prime to assure adequate dilution prior to admixture with the other component. The initial bolus infusion is followed by the administration of a continuous infusion of 250,000 - 500,000 KIU per hour until the end of the operation. In general, the total amount of aprotinin administered per treatment course should not exceed 7 million KIU. Paediatric population - The safety and efficacy in children below 18 years of age have not been established. Refer to Summary of Product Characteristics for use in other specific patient populations. Aprotinin should be infused using a central venous catheter. The same lumen should not be used for the administration of any other medicinal product. When using a multi-lumen central catheter a separate catheter is not required. Aprotinin must be given only to patients in the supine position and must be given slowly (maximum 5 - 10 ml/min) as an intravenous injection or a short infusion. CONTRAINDICATIONS: Hypersensitivity to the active substance or any of the excipients. Patients with a positive aprotinin specific IgG antibody test. If no such test is possible prior to treatment, administration of aprotinin to patients with a suspected previous exposure including in fibrin sealant products during the last 12 months is contraindicated. SPECIAL WARNINGS AND PRECAUTIONS FOR USE: Aprotinin should 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. Laboratory monitoring of anticoagulation during cardiopulmonary bypass: Aprotinin is not a heparin-sparing agent and it is important that adequate anticoagulation with heparin be maintained during aprotinin-therapy. Elevations in the partial thromboplastin time (PTT) and celite. Activated Clotting Time (Celite ACT) are expected in aprotinin-treated patients during surgery, and in the hours after surgery. Therefore, the partial thromboplastin time (PTT) should not be used to maintain adequate anticoagulation with heparin. In patients undergoing cardiopulmonary bypass with aprotinin therapy, one of three methods is recommended to maintain adequate anticoagulation: Activated Clotting Time (ACT), Fixed Heparin Dosing, or Heparin Titration (see below). If activated clotting time (ACT) is used to maintain adequate anticoagulation, a minimal celite-ACT of 750 seconds or kaolin-ACT of 480 seconds, independent of the effects of haemodilution and hypothermia, is recommended in the presence of aprotinin. Important: aprotinin is not a heparin-sparing agent. Graft Conservation: Blood drawn from the aprotinin central infusion line should not be used for graft preservation. Re-exposure to aprotinin: Administration of aprotinin, especially to patients who have received