Prophylactically to reduce perioperative blood loss in patients undergoing coronary artery bypass surgery.
Composition:
1 shoe 50 ml contains a concentrated aprotinin solution with an activity of 277.8 units of Ph.Eur., Corresponding to 500,000 KIU (kallikrein inactivation units).
Action:
Aprotinin is a 58 amino acid polypeptide derived from bovine lung. Being a protease inhibitor and forming enzyme-inhibitor complexes, the drug acts as an inhibitor of human trypsin, plasmin, plasma and tissue kallikrein. The binding of aprotinin to the enzyme also occurs when the enzyme is combined with another protein under the condition that the active site is available and thus aprotinin inhibits not only free plasmin but also the plasm-streptokinase complex. After intravenous administration, aprotinin undergoes rapid distribution in the total extracellular space, which initially leads to a decrease in its plasma concentration with an initial T0,5 0.3-0.7 h. T0,5 in the elimination phase is 5-10 h. Antifibrinolytic activity in 80% occurs in connection with plasma proteins, and in 20% in the protein-free fraction. Aprotinin accumulates in the kidneys and, to a lesser extent, in cartilage. It practically does not penetrate into the cerebrospinal fluid. Aprotinin is metabolised to shorter peptides and amino acids with lysosomal enzymes in the kidney. 25-40% of the drug is excreted in the urine in the form of inactive metabolites, and less than 5% in the active form.
Contraindications:
Hypersensitivity to aprotinin.
Precautions:
Special care should be taken in patients who have received past or prescribed aprotinin and in patients with any allergic history. In this group of patients, intravenous administration of drugs from the group of H receptor antagonists is recommended1 or H2 and administration of aprotinin as described under "Dosage". Special care should also be taken in patients undergoing aortic arch reconstruction under conditions of complete cardiac arrest with profound hypothermia - increased mortality and more frequent renal failure have been observed. The condition for administration of aprotinin is to maintain proper anti-coagulant therapy (heparin) and monitor this therapy. It is recommended that ACT with the use of celite as an activator be maintained at> 750 s at the time when extracorporeal circulation is used. Due to the effect of aprotinin on the results of ACT tests, alternative methods of determining the Heparin demand may be used. Due to the possibility of occlusion of the venous graft after aprotinin, proper transplantation is necessary (it must not be stored in blood-containing solutions that have been taken from the aprotinin-previously administered line). Particularly cautiously used in patients with severe renal impairment, no dose adjustment is necessary in patients with impaired renal function. The effectiveness and safety of the medicine in children is not fully known.
Pregnancy and lactation:
During pregnancy, use only in cases of danger to the mother's life. There are no data on the excretion of aprotinin in breast milk; if you need to give your mother a breastfeeding drug, she should stop breast-feeding during and for 48 hours after stopping the medicine.
Side effects:
Allergic reactions, including anaphylactic reactions with varying severity of symptoms (from skin lesions, nausea, dyspnoea to full anaphylactic shock) - they occur rarely after the first administration, but in the case of re-administration may already occur frequently (5% of patients) - if they occur you should stop taking the medicine immediately. Approximately 50% of patients after the first administration of the drug were found to have specific antibodies directed against aprotinin. Transient increases in serum creatinine, occasionally transient renal failure have been observed. There was an increased risk of myocardial infarction, probably due to a decrease in heparin concentration due to the use of celite as an activator for ACT.An increased risk of vascular graft closure was found as a result of not just the side effect of the drug, but the use of inadequate heparin doses or improper maintenance of the venous graft. Cardiac arrhythmia (ventricular and supraventricular tachycardia), cardiac insufficiency, cardiac arrest, hypotension have been rarely observed. Local symptoms of thrombophlebitis.
Dosage:
Prior to each administration, 1 ml (5.6 U of Ph. Eur. = 10,000 KIU) aprotinin should be administered to the patient, followed by observation for 10 min, especially if aprotinin has been used before or if this is not possible with certainly exclude. Patients undergoing coronary artery bypass surgery: the first dose is 1111 U. Ph. Eur. (2,000,000 KIU) by intravenous infusion over 20 minutes at the beginning of the surgical procedure; then the drug is continued using a continuous infusion of 277.8 Upha. Eur. (500,000 KIU) for 1 h until the end of the surgical procedure; another 1 111,1 j. Ph. Eur. (2,000,000 KIU) is added to the filling fluids of extracorporeal circulation equipment. The product should be administered slowly (with the maximum infusion rate of 10 ml / min) in a long injection or short intravenous infusion, only to patients who are lying down. As a general rule, the preparation should not be administered for longer than 6 hours during coronary artery bypass surgery using extracorporeal circulation.
(C)
