No

Blood Product Derivative; Hemostatic Agent

Reduction or prevention of blood loss in patients undergoing coronary artery bypass surgery when a high risk of excessive bleeding exists, including open heart reoperation, pre-existing coagulopathies, operations on the great vessels, and when a patient's beliefs prohibit blood transfusions

B

Hypersensitivity to aprotinin or any component

Anaphylactic reactions are possible. Hypersensitivity reactions are more common with repeated use especially when re-exposure is within 6 months. All patients should receive a test dose at least 10 minutes before loading dose. Patients with a history of allergic reactions to drugs or other agents may be more likely to develop a reaction.

1% to 10%

Cardiovascular: Atrial fibrillation, myocardial infarction, heart failure, atrial flutter, ventricular tachycardia, hypotension, supraventricular tachycardia

Central nervous system: Fever, mental confusion

Local: Phlebitis

Renal: Increased potential for postoperative renal dysfunction

Respiratory: Dyspnea, bronchoconstriction

<1% (Limited to important or life-threatening symptoms): Cerebral embolism, cerebrovascular events, convulsions, hemolysis, liver damage, pulmonary edema

Maximum amount of aprotinin that can safely be given has not yet been determined. One case report of aprotinin overdose was associated with the development of hepatic and renal failure and eventually death. Autopsy demonstrated severe hepatic necrosis and extensive renal tubular and glomerular necrosis. The relationship with these findings and aprotinin remains unclear.

Heparin and aprotinin prolong ACT. The ACT becomes a poor measure of adequate anticoagulation with the concurrent use of these drugs.

Fibrinolytic drugs may have poorer activity. Aprotinin blocks this fibrinolytic activity; avoid concurrent use.

Captopril's antihypertensive effects may be blocked; avoid concurrent use.

Vials should be stored between 2°C and 25°C and protected from freezing; it is incompatible with corticosteroids, heparin, tetracyclines, amino acid solutions, and fat emulsion

Serine protease inhibitor; inhibits plasmin, kallikrein, and platelet activation producing antifibrinolytic effects; a weak inhibitor of plasma pseudocholinesterase. It also inhibits the contact phase activation of coagulation and preserves adhesive platelet glycoproteins making them resistant to damage from increased circulating plasmin or mechanical injury occurring during bypass

Half-life: 150 minutes

Elimination: By the kidney

Test dose: All patients should receive a 1 mL I.V. test dose at least 10 minutes prior to the loading dose to assess the potential for allergic reactions

Regimen A (standard dose):

2 million units (280 mg) loading dose I.V. over 20-30 minutes

2 million units (280 mg) into pump prime volume

500,000 units/hour (70 mg/hour) I.V. during operation

Regimen B (low dose):

1 million units (140 mg) loading dose I.V. over 20-30 minutes

1 million units (140 mg) into pump prime volume

250,000 units/hour (35 mg/hour) I.V. during operation

Bleeding times, prothrombin time, activated clotting time, platelet count, red blood cell counts, hematocrit, hemoglobin and fibrinogen degradation products; for toxicity also include renal function tests and blood pressure

Antiplasmin effects occur when plasma aprotinin concentrations are 125 KIU/mL and antikallikrein effects occur when plasma levels are 250-500 KIU/mL; it remains unknown if these plasma concentrations are required for clinical benefits to occur during cardiopulmonary bypass

Aprotinin prolongs whole blood clotting time of heparinized blood as determined by the Hemochrom® method or similar surface activation methods. Patients may require additional heparin even in the presence of activated clotting time levels that appear to represent adequate anticoagulation.

No information available to require special precautions

No effects or complications reported

You will be unaware of the effects of this drug, however, you will be closely monitored at all times. Breast-feeding precautions: Consult prescriber if breast-feeding.

All intravenous doses should be administered through a central line

Injection: 1.4 mg/mL [10,000 units/mL] (100 mL, 200 mL)

Bidstrup BP, Royston D, Sapsford RN, et al, "Reduction in Blood Loss and Blood Use After Cardiovascular Bypass With High Dose Aprotinin," J Thorac Cardiovasc Surg, 1989, 97(3):364-72.

Boldt J, "Endothelial-Related Coagulation in Pediatric Surgery," Ann Thorac Surg, 1998, 65(6 Suppl):S56-9.

Carrel TP, Schwanda M, Vogt P, et al, "Aprotinin in Pediatric Cardiac Operations: A Benefit in Complex Malformations and With High-Dose Regimen Only," Ann Thorac Surg, 1998, 66(1):153-8.

Cosgrove DM 3d, Heric B, Lytle BW, et al, "Aprotinin Therapy for Reoperative Myocardial Revascularization: A Placebo-Controlled Study," Ann Thorac Surg, 1992, 54(6):1031-6.

Huang H, Ding W, Su Z, et al, "Mechanism of the Preserving Effect of Aprotinin on Platelet Function and Its Use in Cardiac Surgery," J Thorac Cardiovasc Surg. 1993, 106(1):11-8.

Miller BE, Tosone SR, Tam VK, et al, "Hematologic and Economic Impact of Aprotinin in Reoperative Pediatric Cardiac Operations," Ann Thorac Surg, 1998, 66(2):535-41.

Penkoske P, Entwistle LM, Marchak BE, et al, "Aprotinin in Children Undergoing Repair of Congenital Heart Defects," Ann Thorac Surg, 1995, 60(6 Suppl):S529-32.

Schulze K, Graeter T, Schaps D, et al, "Severe Anaphylactic Shock Due to Repeated Application of Aprotinin in Patients Following Intrathoracic Aortic Replacement," Eur J Cardiothorac Surg, 1993, 7(9):495-6.

Spray TL, "Use of Aprotinin in Pediatric Organ Transplantation," Ann Thorac Surg, 1998, 65(6 Suppl):S71-3.

Verstraete M, "Clinical Application of Inhibitors of Fibrinolysis," Drugs, 1985, 29(3):236-61.

Viby-Mogensen J, "Interaction of Other Drugs With Muscle Relaxants," Semin Anesth, 1985, 4:52-64.

Woodman RC and Harker LA, "Bleeding Complications Associated With Cardiopulmonary Bypass," Blood, 1990, 76(9):1680-97.