Coagulation factor viia

NOVOSEVEN RT, Coagulation Factor VIIa (Recombinant), is indicated for: • Treatment of bleeding episodes and peri-operative management in adults and children with hemophilia A or B with inhibitors, congenital Factor VII (FVII) deficiency, and Glanzmann’s thrombasthenia with refractoriness to platelet transfusions, with or without antibodies to platelets. • Treatment of bleeding episodes and peri-operative management in adults with acquired hemophilia. NOVOSEVEN RT, Coagulation Factor VIIa (Recombinant) is indicated for: • Treatment of bleeding episodes and perioperative management in adults and children with hemophilia A or B with inhibitors, congenital Factor VII (FVII) deficiency, and Glanzmann’s thrombasthenia with refractoriness to platelet transfusions, with or without antibodies to platelets.

NOVOSEVEN RT is recombinant Factor VIIa and, when complexed with tissue factor can activate coagulation Factor X to Factor Xa, as well as coagulation Factor IX to Factor IXa. Factor Xa, in complex with other factors, then converts prothrombin to thrombin, which leads to the formation of a hemostatic plug by converting fibrinogen to fibrin and thereby inducing local hemostasis. This process may also occur on the surface of activated platelets.

For intravenous administration only For intravenous injection only Bleeding Episodes. Indication Dosing Recommendation Congenital Hemophilia A or B with Inhibitors • 90 mcg/kg every 2 hours, adjustable based on severity of bleeding until hemostasis is achieved • 90 mcg/kg every 3-6 hours after hemostasis is achieved for severe bleeds Acquired Hemophilia • 70-90 mcg/kg every 2-3 hours until hemostasis is achieved Congenital Factor VII Deficiency • 15-30 mcg/kg every 4-6 hours until hemostasis is achieved Glanzmann’s Thrombasthenia • 90 mcg/kg every 2-6 hours until hemostasis is achieved Peri-operative Management.

None known. None known

Boxed warning (thrombosis •): Serious arterial and venous thrombotic events following administration of NOVOSEVEN RT have been reported. • Discuss the risks and explain the signs and symptoms of thrombotic and thromboembolic events to patients who will receive NOVOSEVEN RT. • Monitor patients for signs or symptoms of activation of the coagulation system and for thrombosis. • Hypersensitivity reactions, including anaphylaxis, can occur with NOVOSEVEN RT. Discontinue infusion and administer appropriate treatment if symptoms appear. • Antibody to FVII may occur in FVII deficient patients. Monitor Factor VII deficient patients for prothrombin time (PT) and FVII coagulant activity, and for antibody formation to NOVOSEVEN RT

The most common and serious adverse reactions in clinical trials are thrombotic events. Thrombotic adverse reactions following the administration of NOVOSEVEN in clinical trials occurred in 4% of patients with acquired hemophilia and 0.2% of bleeding episodes in patients with congenital hemophilia.

• Avoid simultaneous use of activated prothrombin complex concentrates. • Do not mix NOVOSEVEN RT with infusion solutions. • Thrombosis may occur if NOVOSEVEN RT is administered concomitantly with Coagulation Factor XIII. • Avoid simultaneous use of NOVOSEVEN RT and aPCCs (activated prothrombin complex concentrates). • Do not administer NOVOSEVEN RT with coagulation factor XIII (FXIII)

Do not freeze. Prior to reconstitution, store NOVOSEVEN RT powder and histidine diluent between 2-25°C (36-77°F). Store protected from light. After reconstitution, store NOVOSEVEN RT either at room temperature or refrigerated for up to 3 hours. Do not freeze reconstituted NOVOSEVEN RT or store in syringes.