Adult Dosing

Hemophilia A or B with Inhibitors

Treatment of acute bleeding episodes

• 90 mcg/kg IV q2 hrs, until hemostasis is achieved
• Dose range: 35-120 mcg/kg
• Post-hemostatic dose: Continue dosing q3-6 hrs, for severe bleeds, to maintain the hemostatic plug

• The minimum effective dose has not been established
• The duration of post-hemostatic dosing should be minimized
• Therapy should be administered to patients only under the supervision of a physician well trained in the treatment of bleeding disorders

Minor Surgery

• Start with 90 mcg/kg IV immediately before surgical intervention, repeat q2 hrs during surgery
• Post-surgery: Bolus injection q2 hrs x 2 days; then q2-6 hrs until healing has occurred

Major Surgery

• Start with 90 mcg/kg IV immediately before surgical intervention, repeat q2 hrs during surgery
• Post-surgery: Bolus injection q2 hrs x 5 days; then q4 hrs until healing has occurred

Congenital factor VII deficiency (bleeding episode or surgical bleeding prophylaxis)

• Dose range: 15-30 mcg/kg IV q4-6 hrs until hemostasis is achieved

• Dose and frequency of injections should be adjusted to each individual
• Minimum effective dose has not been determined
• Therapy should be administered to patients only under the supervision of a physician well trained in the treatment of bleeding disorders

Acquired hemophilia (bleeding episode or surgical bleeding prophylaxis)

• Dose range: 70-90 mcg/kg IV q2-3 hrs until hemostasis is achieved

• Dose and frequency of injections should be adjusted to each individual
• Minimum effective dose has not been determined
• Therapy should be administered to patients only under the supervision of a physician well trained in the treatment of bleeding disorders

Pediatric Dosing

Hemophilia A or B with Inhibitors

Treatment of acute bleeding episodes

• 90 mcg/kg IV q2 hrs, until hemostasis is achieved
• Dose range: 35-120 mcg/kg
• Post-hemostatic dose: Continue dosing q3-6 hrs, for severe bleeds, to maintain the hemostatic plug

• The minimum effective dose has not been established
• The duration of post-hemostatic dosing should be minimized
• Therapy should be administered to patients only under the supervision of a physician well trained in the treatment of bleeding disorders

Minor Surgery

• Start with 90 mcg/kg IV immediately before surgical intervention, repeat q2 hrs during surgery
• Post-surgery: Bolus injection q2 hrs x 2 days; then q2-6 hrs until healing has occurred

Major Surgery

• Start with 90 mcg/kg IV immediately before surgical intervention, repeat q2 hrs during surgery
• Post-surgery: Bolus injection q2 hrs x 5 days; then q4 hrs until healing has occurred

Congenital factor VII deficiency (bleeding episode or surgical bleeding prophylaxis)

• Dose range: 15-30 mcg/kg IV q4-6 hrs until hemostasis is achieved

• Dose and frequency of injections should be adjusted to each individual
• Minimum effective dose has not been determined
• Therapy should be administered to patients only under the supervision of a physician well trained in the treatment of bleeding disorders

Acquired hemophilia (bleeding episode or surgical bleeding prophylaxis)

• Dose range: 70-90 mcg/kg IV q2-3 hrs until hemostasis is achieved

• Dose and frequency of injections should be adjusted to each individual
• Minimum effective dose has not been determined
• Therapy should be administered to patients only under the supervision of a physician well trained in the treatment of bleeding disorders

[Outline]

• Adult Dosing
• Pediatric Dosing

• Treatment of bleeding episodes in hemophilia A or B patients with inhibitors to factor VIII or factor IX and in patients with acquired hemophilia
• Prevention of bleeding in surgical interventions or invasive procedures in hemophilia A or B patients with inhibitors to factor VIII or factor IX and in patients with acquired hemophilia
• Treatment of bleeding episodes in patients with congenital FVII deficiency
• Prevention of bleeding in surgical interventions or invasive procedures in patients with congenital FVII deficiency

• Hypersensitivity to any of the ingredients of the product
• Hypersensitivity to mouse, hamster, or bovine proteins (NovoSeven)

• During postmarketing surveillance, arterial and venous thrombotic and thromboembolic events have been reported following administration of Coagulation Factor VIIa. Increased risk of arterial thromboembolic adverse events, both fatal and non-fatal, has been reported when administered outside the current approved indications. Risks and the signs and symptoms of thrombotic and thromboembolic events should be discussed with the patients who will receive Coagulation Factor VIIa. Monitor patients for signs or symptoms of activation of the coagulation system and for thrombosis. Safety and efficacy outside the approved indications has not been established

Renal Dose Adjustment

• Renal impairment: Dose adjustments not defined

Hepatic Dose Adjustment

• Hepatic impairment: Caution advised; dose adjustments not defined

See Supplemental Patient Information

• Thrombotic events have been reported following the administration of Coagulation Factor VIIa within the licensed indications. Patients with DIC, advanced atherosclerotic disease, crush injury, septicemia, or concomitant treatment with aPCCs/PCCs (activated or nonactivated prothrombin complex concentrates) are at higher risk. Monitor patients for development of signs or symptoms of activation of coagulation system or thrombosis; if evidence of intravascular coagulation and clinical thrombosis is reported, reduce the dose or stop the treatment
• Serious thrombotic adverse events have been reported with the use of Coagulation Factor VIIa outside the labeled indications such as to control bleeding in intracerebral hemorrhage, advanced liver disease, trauma, cardiac surgery, spinal surgery, postpartum hemorrhage and other therapeutic areas [US Black Box Warning]
• Monitor prothrombin time (PT) and factor VII coagulant activity before and after administration of Coagulation Factor VIIa. Suspect antibody formation and perform analysis for antibodies if PT is not corrected or bleeding is not controlled after treatment with the recommended doses
• Administer with caution in patients with known hypersensitivity to any of the ingredients of the product or in patients with known hypersensitivity to hamster, mouse, or bovine proteins (NovoSeven RT)
• Laboratory coagulation parameters including prothrombin time (PT/INR), activated partial thromboplastin time (aPTT), and plasma FVII clotting activity (FVII:C) show no direct correlation to achieving hemostasis; they may give different results with different reagents

Cautions: Use cautiously in

• History of coronary heart disease
• Liver disease
• Disseminated intravascular coagulation
• Post-operative immobilization
• Elderly patients
• Neonates
• Prolonged post-hemostatic dosing
• Advanced atherosclerotic disease
• Crush injury
• Septicemia
• Concomitant prothrombin complex concentrate use

Supplemental Patient Information

• Inform patients of the early signs and symptoms of hypersensitivity reactions including hives, urticaria, chest tightness, wheezing, hypotension, tachycardia, and anaphylaxis. Advise patients to discontinue the drug and immediately contact their clinician for appropriate emergency care, depending on the severity of reaction, if such symptoms occur
• Warn patients about the signs of thrombosis including new onset swelling and pain in the limbs or abdomen, shortness of breath, new onset chest pain, loss of sensation or motor power, or altered consciousness or speech. Advise patients to seek medical help if any such signs or symptoms occur

Pregnancy Category:C

Breastfeeding: Safety unknown. It is unknown whether Coagulation Factor VIIa [Recombinant] is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, taking into account the importance of the drug to the mother, a decision should be made whether to discontinue nursing or to discontinue the drug.

• CV: Thromboembolism, hypertension, hypotension, cerebral artery occlusion, cerebrovascular accident, pulmonary embolism, shock, deep vein thrombosis, angina pectoris, bradycardia
• CNS: Headache
• GI: Nausea, vomiting
• DERM: Rash, pruritus, urticaria
• RESP: Pneumonia
• HEMA: DIC, hemorrhage, coagulopathy, decreased plasma fibrinogen
• MUSC: Arthralgia, hemarthrosis
• GU: Renal failure
• LOCAL: Injection site reaction, pain, thrombophlebitis
• HYPERSENSITIVITY: Anaphylaxis, hypersensitivity reactions
• MISC: Pyrexia, edema

• Coagulation factor/thrombotic agent; activates coagulation factor X to factor Xa and coagulation factor IX to factor IXa, factor Xa, in complex with other factors, then converts prothrombin to thrombin leading to the formation of a hemostatic plug by converting fibrinogen to fibrin, thus inducing local hemostasis
• Metabolism: Unknown
• Excretion: Unknown
• Half-life
• Healthy subjects: 3.9-6 hrs
• Hemophilia A or B: 2.3 hrs (range 1.7-2.7)

US Trade Name(s)

• NovoSeven RT
• NovoSeven

US Availability

NovoSeven RT

• PWDR for INJ: 1 mg/vial
• PWDR for INJ: 2 mg/vial
• PWDR for INJ: 5 mg/vial

NovoSeven

• PWDR for INJ: 1.2 mg/vial
• PWDR for INJ: 2.4 mg/vial
• PWDR for INJ: 4.8 mg/vial

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• N/A

UK Availability

• N/A

Australian Trade Name(s)

• NovoSeven RT

Australian Availability

NovoSeven RT

• PWDR for INJ: 1 mg/vial
• PWDR for INJ: 2 mg/vial
• PWDR for INJ: 5 mg/vial

[Outline]

Hematology/Oncology

Coagulation Factor/thrombotic Agent