Factor VIIa (Recombinant)
Medically reviewed by Drugs.com. Last updated on Dec 3, 2018.
(FAK ter SEV en aye ree KOM be nant)
- Coagulation Factor VIIa
- Eptacog Alfa (Activated)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
NovoSeven RT: 1 mg (1 ea); 2 mg (1 ea); 5 mg (1 ea); 8 mg (1 ea) [contains polysorbate 80]
Brand Names: U.S.
- NovoSeven RT
- Antihemophilic Agent
Recombinant factor VIIa, a vitamin K-dependent glycoprotein, promotes hemostasis by activating the extrinsic pathway of the coagulation cascade. It replaces deficient activated coagulation factor VII, which complexes with tissue factor and may activate coagulation factor X to Xa and factor IX to IXa. When complexed with other factors, coagulation factor Xa converts prothrombin to thrombin, a key step in the formation of a fibrin-platelet hemostatic plug.
Hemophilia A or B: Vss: Children 2 to 12 years: 164 mL/kg; Adults: 107 to 128 mL/kg
Factor VII deficiency: Vss: 280 to 290 mL/kg
Hemophilia A or B: Clearance: Children 2 to 12 years: 58 mL/hour/kg; Adults: 31 to 39 mL/hour/kg
Factor VII deficiency: Clearance: 71 to 79 mL/kg/hour
Hemophilia A or B: Half-life, terminal: Children 2 to 12 years: 2.6 hours; Adults: 2.9 to 3.1 hours
Factor VII deficiency: Half-life, terminal: 2.8 to 3.1 hours
Use: Labeled Indications
Bleeding episodes and perioperative management: 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; treatment of bleeding episodes and perioperative management in adults with acquired hemophilia.
Off Label Uses
Intracranial hemorrhage associated with danaparoid
Based on the Neurocritical Care Society and the Society of Critical Care Medicine guideline for reversal of antithrombotics in intracranial hemorrhage, factor VIIa (recombinant) is recommended to reverse the anticoagulant effect following intracranial hemorrhage associated with danaparoid. Of note, in patients receiving LMWH for prophylaxis (ie, not a full therapeutic dose), the NCS/SCCM guidelines suggest against reversal (danaparoid is a heparinoid with a similar action to the LMWHs).
Refractory bleeding after cardiac surgery in nonhemophiliac patients
Data from a limited number of patients (retrospective cohort study) suggests that factor VIIa (recombinant) may be beneficial for the management of patients with this condition [Chapman 2011], [Karkouti 2007]. Additional data may be necessary to further define the role of factor VIIa (recombinant) in the treatment of this condition.
Based on Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists Blood Conservation Clinical Practice Guidelines, factor VIIa (recombinant) is effective and recommended for the treatment of refractory bleeding after cardiac surgery in nonhemophiliac patients.
Warfarin-related intracerebral hemorrhage
Although preliminary data from a limited number of patients suggested that factor VIIa (recombinant) may be beneficial for the management of patients with warfarin-related intracerebral hemorrhage, [Freeman 2004], [Ilyas 2008] factor VIIa (recombinant) does not replenish all the vitamin-K dependent clotting factors and does not restore thrombin generation as well as prothrombin complex concentrates (PCCs), and therefore may not be ideal.
There are no contraindications listed in the manufacturer’s labeling.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to eptacog alfa, any component of the formulation, or mouse, hamster or bovine protein
Congenital hemophilia A or B with inhibitors:
Bleeding episodes: 90 mcg/kg/dose every 2 hours until hemostasis is achieved or until the treatment is judged ineffective. Doses between 35 and 90 mcg/kg/dose have been used successfully in clinical trials. The dose, interval, and duration of therapy may be adjusted based upon the severity of bleeding and the degree of hemostasis achieved. For patients experiencing severe bleeds, dosing should be continued at 3- to 6-hour intervals post-hemostasis. The duration of any post-hemostatic dosing should be minimized.
Perioperative management: 90 mcg/kg/dose immediately before surgery (additional bolus doses may be administered for major surgery if required); repeat at 2-hour intervals for the duration of surgery. For minor surgery, continue 90 mcg/kg/dose postoperatively every 2 hours for 48 hours, then every 2 to 6 hours until healed. For major surgery, continue 90 mcg/kg/dose postoperatively every 2 hours for 5 days, then every 4 hours or by continuous infusion at 50 mcg/kg/hour until healed.
Congenital factor VII deficiency:
Bleeding episodes: 15 to 30 mcg/kg/dose every 4 to 6 hours until hemostasis is achieved. Doses as low as 10 mcg/kg have been effective.
Perioperative management: 15 to 30 mcg/kg/dose immediately before surgery; repeat every 4 to 6 hours for the duration of surgery and until hemostasis achieved. Doses as low as 10 mcg/kg have been effective.
Bleeding episodes: 70 to 90 mcg/kg/dose every 2 to 3 hours until hemostasis is achieved.
Perioperative management: 70 to 90 mcg/kg/dose immediately before surgery; repeat every 2 to 3 hours for the duration of surgery and until hemostasis achieved.
Bleeding episodes (severe, refractory to platelet transfusions): 90 mcg/kg/dose every 2 to 6 hours until hemostasis is achieved.
Perioperative management: 90 mcg/kg/dose immediately before surgery; repeat at 2-hour intervals for the duration of surgery. Continue 90 mcg/kg/dose every 2 to 6 hours to prevent postoperative bleeding. Note: Higher doses (100 to 140 mcg/kg) may be used for surgical patients who have clinical refractoriness with or without platelet-specific antibodies compared to those with neither.
Intracranial hemorrhage associated with danaparoid (off-label use): IV: 90 mcg/kg once (NCS/SCCM [Frontera 2016]).
Refractory bleeding after cardiac surgery in nonhemophiliac patients (off-label use): Dosing not established; doses in the range of 35 to 70 mcg/kg/dose have been recommended based on low-quality evidence (case series, observational studies) (Chapman 2011; Ferraris 2011; Karkouti 2007); in patients with a left ventricular assist device, lower doses (ie, 10 to 20 mcg/kg) may be preferred to reduce thromboembolic events (Bruckner 2009).
Refer to adult dosing.
Hemophilia A or B (congenital) with inhibitors: Infants, Children, and Adolescents: IV:
Bleeding episodes: 90 mcg/kg every 2 hours until hemostasis is achieved or until the treatment is judged ineffective. Doses between 35 to 90 mcg/kg have been used successfully in clinical trials. The dose, interval, and duration of therapy may be adjusted based on severity of bleeding and the degree of hemostasis achieved. For patients treated for joint or muscle bleeds, a decision on the outcome of treatment was reached within 8 doses in the majority of patients, although more doses were required for severe bleeds; adverse effects were reported most commonly in patients treated with 12 or more doses. For patients experiencing severe bleeds to maintain the hemostatic plug, dosing should be continued at 3- to 6-hour intervals; the duration of posthemostatic dosing should be minimized.
Perioperative management: 90 mcg/kg immediately before surgery (additional bolus doses may be administered for major surgery if required); repeat at 2-hour intervals for the duration of surgery. For minor surgery, continue 90 mcg/kg every 2 hours for 48 hours, then every 2 to 6 hours until healed. For major surgery, continue 90 mcg/kg every 2 hours for 5 days, then every 4 hours until healed.
Congenital factor VII deficiency: Infants, Children, and Adolescents: IV:
Bleeding episodes: 15 to 30 mcg/kg every 4 to 6 hours until hemostasis is achieved. Doses as low as 10 mcg/kg have been effective.
Perioperative management: 15 to 30 mcg/kg immediately before surgery; repeat every 4 to 6 hours for the duration of surgery and until hemostasis achieved. Doses as low as 10 mcg/kg have been effective.
Glanzmann's thrombasthenia: Infants, Children, and Adolescents: IV:
Bleeding episodes, severe (refractory to platelet transfusions): 90 mcg/kg/dose every 2 to 6 hours until hemostasis is achieved
Perioperative management: 90 mcg/kg immediately before surgery; repeat at 2-hour intervals for the duration of surgery. Continue 90 mcg/kg/dose every 2 to 6 hours to prevent postoperative bleeding. Note: Higher average infused doses (median: 100 mcg/kg) were noted for surgical patients who had clinical refractoriness with or without platelet-specific antibodies compared to those with neither.
Prior to reconstitution, bring vials to a temperature not above 37°C (98.6°F). Add recommended diluent along wall of vial; do not inject directly onto powder. Gently swirl until dissolved. Do not mix with other infusion solutions. Administer within 3 hours after reconstitution.
NovoSeven RT: Reconstitute each vial to a final concentration of 1 mg/mL using the provided histidine diluent as follows:
1 mg vial: 1.1 mL histidine diluent vial or 1 mL prefilled histidine diluent syringe
2 mg vial: 2.1 mL histidine diluent vial or 2 mL prefilled histidine diluent syringe
5 mg vial: 5.2 mL histidine diluent vial or 5 mL prefilled histidine diluent syringe
8 mg vial: 8.1 mL histidine diluent vial or 8 mL prefilled histidine diluent syringe
IV bolus: Administer over 2 to 5 minutes (depending on the dose). Use NS to flush line (if necessary) before and after administration.
IV infusion: Refer to perioperative management of patients with congenital hemophilia A or B in dosing for detailed recommendations. Use NS to flush line (if necessary) before and after administration.
Some products may contain sodium.
NovoSeven RT: Prior to reconstitution, store between 2°C to 25°C (36°F to 77°F); do not freeze. Protect from light. Reconstituted solutions may be stored at room temperature or under refrigeration, but must be infused within 3 hours of reconstitution. Do not freeze reconstituted solutions. Do not store reconstituted solutions in syringes.
Factor XIII A-Subunit (Recombinant): May enhance the thrombogenic effect of Factor VIIa (Recombinant). Monitor therapy
1% to 10%:
Cardiovascular: Thrombosis (4%), hypertension (2%), bradycardia (1%), edema (1%), hypotension (1%)
Central nervous system: Cerebrovascular disease (<2%), headache (1%), pain (1%)
Dermatologic: Pruritus (1%), skin rash (1%)
Endocrine & metabolic: Decreased serum fibrinogen (2%)
Gastrointestinal: Vomiting (1%)
Hematologic & oncologic: Decreased prothrombin time (1%), disseminated intravascular coagulation (1%), increased fibrinolysis (1%), purpura (1%)
Hepatic: Abnormal hepatic function tests (<2%)
Hypersensitivity: Hypersensitivity reaction (1%)
Local: Injection site reaction (1%)
Neuromuscular & skeletal: Osteoarthrosis (1%)
Renal: Renal function abnormality (1%)
Respiratory: Pneumonia (1%)
Miscellaneous: Fever (4%), decreased therapeutic response (<2%)
<1%, postmarketing, and/or case reports: Anaphylactic shock, anaphylaxis, angina pectoris, angioedema, antibody development, arterial embolism (retinal), arterial thrombosis, arterial thrombosis (limb, retinal), arthralgia bowel infarction, cerebral infarction, cerebral ischemia, cerebrovascular accident, deep vein thrombosis, flushing, hepatic artery thrombosis, hypersensitivity, immunogenicity, increased fibrin degradation products (including D-dimer elevation), intracardiac thrombus, local phlebitis, myocardial infarction, myocardial ischemia, nausea, occlusion of cerebral arteries, pain at injection site, peripheral ischemia, portal vein thrombosis, pulmonary embolism, renal artery thrombosis, shock, thrombophlebitis, urticaria, venous thrombosis at injection site
Concerns related to adverse effects:
• Antibody formation: In patients with factor VII deficiency, if factor VIIa activity does not reach the expected level, prothrombin time is not corrected, or bleeding is uncontrolled (with recommended doses), suspect antibody formation and perform antibody analysis. Prothrombin time and factor VII coagulant activity should be measured before and after administration in patients with factor VII deficiency.
• Hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis, have been reported with use. Patients with known hypersensitivity to mouse, hamster, or bovine proteins may be at higher risk. If hypersensitivity reaction occurs, discontinue use and administer appropriate treatment.
• Thromboembolic events: [US Boxed Warning]: Serious arterial and venous thrombotic events following administration of Factor VIIa (recombinant) have been reported. Discuss the risks and explain the signs and symptoms of thrombotic and thromboembolic events to patients who will receive factor VIIa (recombinant). Monitor patients for signs and symptoms of activation of the coagulation system and for thrombosis. All patients receiving factor VIIa should be monitored for signs and symptoms of activation of the coagulation system or thrombosis; thrombotic events may be increased in patients with congenital hemophilia receiving concomitant treatment with activated prothrombin complex concentrates, older patients with acquired hemophilia receiving other hemostatic agents, or patients with a history of cardiac or vascular disease or otherwise predisposed to thrombotic events. Decreased dosage or discontinuation is warranted with confirmed intravascular coagulation or presence of clinical thrombosis.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson, 2002; Lucente 2000; Shelley, 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade, 1986; CDC, 1984). See manufacturer’s labeling.
• Reduced efficacy: A number of factors influence the efficacy of factor VIIa, including hypothermia, thrombocytopenia, acidosis, and the amount of blood products transfused prior to administration (Dunkley, 2008).
Monitor for evidence of hemostasis and thrombosis (including laboratory confirmation of intravascular coagulation, if appropriate). Although the prothrombin time (PT)/INR, aPTT, and factor VII clotting activity have shown no direct correlation with achieving hemostasis, these parameters may be useful as adjunct tests to evaluate efficacy and guide dose or interval adjustments. In factor VII–deficient patients, monitor PT and factor VII clotting activity before and after administration; if the factor VIIa activity fails to reach the expected level, if PT is not corrected, or if bleeding is not controlled after treatment with recommended doses, monitor for factor VII antibodies.
Pregnant patients with inherited bleeding disorders, including factor VII deficiency and Glanzmann’s thrombasthenia, may have an increased risk of bleeding following abortion, antenatal procedures, delivery, and miscarriage; close surveillance is recommended. Patients with factor VII deficiency and severe or abnormal bleeding should be treated with recombinant factor VIIa. Patients with Glanzmann’s thrombasthenia and a history of bleeding can be treated prophylactically with recombinant factor VIIa at delivery (RCOG [Pavord 2017).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Have patient report immediately to prescriber signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), signs of blood clots (numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; angina; shortness of breath; tachycardia; or coughing up blood), severe headache, vision changes, severe dizziness, passing out, abdominal pain, or abdominal edema (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
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- Drug class: miscellaneous coagulation modifiers
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Other brands: NovoSeven RT