Aprotinin use and monitoring

Hypersensitivity to aprotinin: Allergic/anaphylactic reactions are rare in patients with no prior exposure to aprotinin. Administration of aprotinin to patients with a suspected previous exposure including in fibrin sealant products during the last 12 months is contraindicated. In the case of re-exposure, the incidence of allergic/anaphylactic reaction is 5.0% in patients with re-exposure within six months, and 0.9% in cases with re-exposure more than six months after initial administration.1

Please find the summary of product characteristics here for more information.

Monitoring of anticoagulation during cardiopulmonary bypass

Aprotinin is not a heparin-sparing agent and it is important that adequate anticoagulation with heparin is maintained during aprotinin therapy.1

The partial thromboplastin time (PTT) should not be used to maintain adequate anticoagulation with heparin. One of three methods is recommended to maintain adequate anticoagulation:1

  • Fixed Heparin Dosing
  • Heparin Titration
  • Activated Clotting Time (ACT)
    • If ACT is used, a minimal celite-ACT of 750 seconds or kaolin-ACT of 480 seconds is recommended

 

DOSAGE ADMINISTRATION
TEST DOSE 10,000 KIU (1ml) The test dose should be administered intravenously to all patients at least 10 minutes prior to loading dose
LOADING DOSE 1 – 2 million KIU

(2-4 vials of 50 ml)

Slow intravenous injection or infusion over 20-30 minutes after induction of anaesthesia and prior to sternotomy
CONTINOUS INFUSION DURING SURGERY 250,000 – 500,000 KIU per hour

(0.5 to 1 vial per hour)

After the initial bolus infusion (loading dose) until the end of the operation
PUMP PRIME DOSE 1 – 2 million KIU

(2 – 4 vials of 50ml)

TO BE ADDED TO THE PUMP PRIME OF THE HEART-LUNG MACHINE
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

One vial of 50ml of aprotinin contains 500,000 KIU

Aprotinin 10,000 KIU/ml Injection BP. Note: 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 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 4.4 of the SmPC).

References

  1. Aprotinin 10,000 KIU/ml Injection BP Summary of Product Characteristics. Available from: https://www.medicines.org.uk/emc/product/2472/smpc. Accessed December 2020.