NEODOSE

INDICATIONS

• Cardiac surgery in non-hemophiliacs: There is a lack of evidence to support the use of recombinant coagulation factor VIIa as prophylactic or routine use in non-hemophiliac pediatric patients undergoing cardiac surgery. Although the data are mostly observational, the benefits may outweigh the risk as rescue therapy for refractory blood loss in pediatric patients undergoing cardiac surgery. Doses have varied but if recombinant factor VIIa is used the Congenital Cardiac Anesthesia Society Task Force recommends 90 mcg/kg every 2 hours for a maximum of 2 doses based on adult and pediatric clinical studies and pharmacokinetic studies. However, larger doses may be necessary in neonates and infants due to increased volume of distribution.
• Other uses in non-hemophiliacs: Factor VIIa has been used in non-hemophiliac pediatric patients for coagulopathies or hemorrhage primarily during cardiac surgery or liver transplantation. Recombinant factor VIIIa has also been used for hemorrhage in pediatric patients with chronic liver disease or failure, disseminated intravascular coagulation, trauma, intracranial hemorrhage, and bleeding associated with malignancy and prophylaxis prior to invasive procedures. Data are limited to small controlled or observational studies; therefore, the evidence for safety and efficacy are inconclusive.

FDA APPROVED INDICATION

Recombinant Factor VIIa is indicated for perioperative management treatment of bleeding episodes in children with hemophilia A or B with inhibitors, and congenital factor VII deficiency. For Glanzmann’s thrombasthenia with refractoriness to platelet transfusions (with or without antibodies to platelets); platelet transfusions are the primary treatment but recombinant factor VIIa is used in severe bleeding episodes requiring systemic hemostatic therapy until hemostasis is achieved and for perioperative management.

PRECAUTIONS

Serious arterial and venous thrombotic events, including a fatal event, have been reported and caution is advised in patients at increased risk of thromboembolic events or complications (DIC or history of DIC, crush injury, concomitant treatment with activated or nonactivated prothrombin complex concentrates (aPCCs/PCCs), liver disease, postoperative immobilization, and septicemia). Furthermore, caution is advised when using higher doses and when used concomitantly with other coagulants. Neonates in general are at risk for thromboembolic complications. Dose reduction or discontinuation may be necessary. Hypersensitivity reactions, including anaphylaxis, have been reported. Administer only if clearly needed to patients with history of known hypersensitivity to recombinant coagulation factor VIIa, any of the product components, or to mouse, hamster, or bovine proteins. Discontinue if symptoms occur, administer appropriate treatment, and weigh benefit and risks before restarting therapy. Factor VII antibodies may develop leading to ineffectiveness or reduced effectiveness.

ADVERSE EFFECTS

Thrombotic events are the most common and serious adverse reactions; However, no thromboembolic events were observed in 29 neonates with intractable bleeding who were administered recombinant factor VIIa at a dose of 100 mcg/kg every 4 hours (maximum 23 doses). Furthermore, a retrospective study (n=134) of non-hemophilic, non-congenital factor VII deficient neonates demonstrated no increased risk of thrombosis or ischemic events when administered recombinant factor VIIa and other blood products (7.5%) compared with fresh frozen plasma alone (7%).

BLACK BOX WARNING

Serious arterial and venous thrombotic events following administration of recombinant factor VIIa have been reported.

ADMINISTRATION

Administer 1000 mcg/mL solution as an IV bolus over 2 to 5 minutes, depending on the dose administered. Flush line with 0.9% sodium chloride before or after injection (if needed). Do not mix with other infusion solutions.

MONITORING

Monitor prothrombin time and factor VII coagulant activity prior to and following administration in factor VII deficient patients. Evaluate for antibodies if expected levels are not reached, prothrombin time is not corrected, or bleeding is uncontrolled. Evaluate hemostasis as indicator of efficacy and to determine treatment schedule; coagulation parameters do not necessarily correlate with or predict effectiveness. Monitor for signs or symptoms of thrombosis or activation of the coagulation system.