Coagulation Factor Viia Recombinant Human
FDA Drug Information • Also known as: Sevenfact
- Brand Names
- Sevenfact
- Route
- INTRAVENOUS
- Dosage Form
- KIT
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
WARNING: THROMBOSIS ● Serious arterial and venous thrombotic events may occur following administration of SEVENFACT ® . [See Warnings and Precautions ( 5.1 )] ● Discuss the risks and explain the signs and symptoms of thrombotic and thromboembolic events to patients who will receive SEVENFACT ® . ● Monitor patients for signs or symptoms of activation of the coagulation system and for thrombosis. WARNING: THROMBOSIS See full prescribing information for complete boxed warning. ● Serious arterial and venous thrombotic events may occur following administration of SEVENFACT ® ( 5.1 ). ● Discuss the risks and explain the signs and symptoms of thrombotic and thromboembolic events to patients who will receive SEVENFACT ® . ● Monitor patients for signs or symptoms of activation of the coagulation system and for thrombosis.
Description
11 DESCRIPTION SEVENFACT [coagulation factor VIIa (recombinant)-jncw] is a sterile, white to off-white lyophilized powder in a single-dose vial containing either 1 mg, 2 mg or 5 mg of coagulation factor VIIa (recombinant)-jncw as the active ingredient. SEVENFACT is to be reconstituted with Sterile Water for Injection in a pre-filled syringe supplied with the product. The reconstituted product is a clear to slightly opaque solution of coagulation factor VIIa (recombinant)-jncw at a concentration of 1 mg of protein per mL with a pH of approximately 6.0. SEVENFACT is formulated with arginine, isoleucine, citrate, glycine, lysine and polysorbate 80. It does not contain any antimicrobial preservatives nor human or bovine plasma-derived proteins. The active ingredient in SEVENFACT, activated coagulation Factor VII, is a glycoprotein of 406 amino acids with a molecular weight of approximately 50 kilodaltons. The amino acid sequence of activated coagulation Factor VII is identical to that of human plasma-derived Factor VIIa. It is >99% pure with a nominal specific activity of 45,000 IU/mg of protein when tested against the World Health Organization international standard for human Factor VIIa activity. SEVENFACT is produced by recombinant DNA technology using genetically engineered rabbits into which the DNA coding sequence for human Factor VII has been introduced. Human Factor VII is expressed in the rabbit mammary gland and secreted into the milk. During purification and processing, Factor VII is enzymatically converted to activated Factor VII. The manufacturing process of SEVENFACT includes specific steps to reduce impurities. SEVENFACT may contain trace amounts of rabbit proteins. The purification process also includes steps that are validated to inactivate or remove viruses, such as Xenotropic murine leukemia virus (X-MuLV), bovine viral diarrhea virus (BVDV), Pseudorabies virus (PRV), Feline Calicivirus (FCV), and Porcine Parvovirus (PPV).
What Is Coagulation Factor Viia Recombinant Human Used For?
1 INDICATIONS AND USAGE SEVENFACT is indicated for the treatment and control of bleeding episodes occurring in adults and adolescents 12 years of age and older with hemophilia A or B with inhibitors. Limitation s of Use: SEVENFACT is not indicated for the treatment of patients with congenital Factor VII deficiency. SEVENFACT is a coagulation factor VIIa concentrate indicated for the treatment and control of bleeding episodes occurring in adults and adolescents 12 years of age and older with hemophilia A or B with inhibitors ( 1 ). Limitation s of Use: SEVENFACT is not indicated for treatment of congenital factor VII deficiency.
Dosage and Administration
2 DOSAGE AND ADMINISTRATION For i ntravenous u se after reconstitution only . Type of Bleeding Dosing Regimen Recommendation For Mild or Moderate bleeds 75 mcg/kg repeated every 3 hours until hemostasis is achieved or Initial dose of 225 mcg/kg. If hemostasis is not achieved within 9 hours, additional 75 mcg/kg doses may be administered every 3 hours as needed to achieve hemostasis For Severe bleeds 225 mcg/kg, followed if necessary 6 hours later with 75 mcg/kg every 2 hours Consider alternative treatments if successful control of bleeding does not occur within 24 hours of the first administration of SEVENFACT. The vial includes a rubber stopper under the plastic cap. The syringe plunger rod has a wide top end and threaded end. The pre-filled syringe with Water for Injection diluent has a plastic backstop, rubber stopper, syringe tip (luer lock top under syringe cap), and syringe cap. The SEVENFACT 1 mg and 2 mg vial adapter and SEVENFACT 5 mg vial adapter each contain a plastic cover, paper protective cover, and spike (under protective paper). 2.1 Dose For intravenous use after reconstitution only. Dose and duration of SEVENFACT depend on the location and severity of the bleeding, need for urgent hemostasis, frequency of administration, and known patient responsiveness to FVIIa-containing bypassing agents during prior bleeding events. Treatment with SEVENFACT should be initiated as soon as a bleeding event occurs. The dose, frequency, and duration of SEVENFACT therapy should be based on the patient’s clinical response and hemostasis evaluation. The use of laboratory assessment(s) of coagulation (PT/INR, aPTT, FVII:C) does not necessarily correlate with or predict the hemostatic effectiveness of SEVENFACT. Dose adjustment may be required if the patient has received other procoagulant therapies prior to treatment with SEVENFACT. Based on the clinical trial program for SEVENFACT, the recommended initial dose should be adjusted based on the criteria provided in Table 1. Table 1 Dosing for Treatment and Control of Bleeding Type of Bleeding Dosing Regimen Recommendation Duration of Therapy Mild and Moderate Joint, superficial muscle, soft tissue and mucous membranes. 75 mcg/kg repeated every 3 hours until hemostasis is achieved or Initial dose of 225 mcg/kg. If hemostasis is not achieved within 9 hours, additional 75 mcg/kg doses may be administered every 3 hours as needed to achieve hemostasis. Consider alternative treatments if successful control of bleeding does not occur within 24 hours of the first administration of SEVENFACT. Continue therapy to support healing and prevent recurrent hemorrhage after hemostasis to maintain the hemostatic plug. The site and severity of bleeding should determine therapy duration. Severe Life or limb threatening hemorrhage, iliopsoas and deep muscle with neurovascular injury, retroperitoneum, intracranial, or gastrointestinal. Patients should seek immediate medical care if signs or symptoms of severe bleeding occur...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The most common adverse reactions (incidence ≥1%) were headache, dizziness, infusion-site discomfort, infusion-site hematoma, infusion-related reaction, and fever ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact HEMA Biologics at 855-718-HEMA (4362) or FDA at 1-800-FDA-1088 or https://www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety database described in this section reflect exposure to SEVENFACT in two clinical studies, Study 1 and Study 2. A total of 42 patients with Hemophilia A or B with or without inhibitors received SEVENFACT: 27 patients in Study 1 at doses 75 mcg/kg and 225 mcg/kg and 15 patients in Study 2 at three escalating dose levels 25 mcg/kg, 75 mcg/kg and 225 mcg/kg [see Clinical Studies ( 14 )] . The most common adverse reactions (incidence ≥1%) reported in clinical trials for SEVENFACT were headache, dizziness, infusion-site discomfort, infusion-site hematoma, infusion-related reaction, and fever. Adverse reactions reported in the two clinical studies are shown in Table 2. Table 2 Adverse Reactions Occurring in Clinical Studies Preferred Terms Number of Patient Adverse Reactions (% Incidence Rate) Study 2 (N=15) Number of A dverse R eactions * Study 2 Number of Patient Adverse Reactions (% Incidence Rate) Study 1 (N=27) Number of A dverse R eactions * Study 1 Infusion site discomfort - - 1 (4) 4 Infusion site hematoma - - 1 (4) 2 Dizziness 1 (7) 2 - - Headache 1 (7) 1 - - Body temperature increase - - 1 (4) 1 Infusion related reaction** 1 (7) 1 - - * Three patients experienced adverse reactions in Study 2 and two patients experienced adverse reactions in Study 1. ** Symptoms resolved without any intervention and did not recur with subsequent administration.
Drug Interactions
7 DRUG INTERACTIONS Clinical experience with pharmacologic use of FVIIa-containing products indicates an elevated risk of serious thrombotic events when used simultaneously with activated prothrombin complex concentrates. Clinical experience with pharmacologic use of FVIIa-containing products indicates an elevated risk of serious thrombotic events when used simultaneously with activated prothrombin complex concentrates ( 7 ).
Contraindications
4 CONTRAINDICATIONS SEVENFACT is contraindicated in patients with: known allergy to rabbits or rabbit proteins. Exposure to SEVENFACT in these patients can result in severe hypersensitivity reaction. severe hypersensitivity reaction to SEVENFACT or any of its components. Exposure to SEVENFACT in these patients can result in severe hypersensitivity reaction. Known allergy to rabbits or rabbit proteins. Severe hypersensitivity reaction to SEVENFACT or any of its components ( 4 ).
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies using SEVENFACT in pregnant women to determine whether there is a drug-associated risk. Animal studies evaluating the embryo-fetal teratogenic potential of SEVENFACT have not been conducted. It is unknown whether SEVENFACT can cause fetal harm when administered to a pregnant woman or can affect fertility. In the U.S. general population, the estimated background risks of major birth defect and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively.
How Supplied
1 6 HOW SUPPLIED/STORAGE AND HANDLING How Supplied SEVENFACT [coagulation factor VIIa (recombinant)-jncw], is supplied as a room temperature stable, white to off-white, lyophilized powder in single-dose vials, one vial per carton. The diluent for reconstitution of SEVENFACT is Water for Injection supplied as a clear colorless solution in a pre-filled syringe. Single 1 mg, 2 mg or 5 mg vials of SEVENFACT are available in packages as indicated in Table 6. Table 6 SEVENFACT Presentations Presentation Cap Color Indication NDC Number Contents 1 mg per vial Yellow NDC 71127-1000-1 One 1 mg SEVENFACT single-dose vial [NDC 71127-1100-1] One pre-filled syringe containing 1.1 mL of Sterile Water for Injection [NDC 71127-1200-1] One 13 mm vial adapter with 5 micron filter 2 mg per vial Green NDC 71127-2000-1 One 2 mg SEVENFACT single-dose vial [NDC 71127-2100-1] One pre-filled syringe containing 2.2 mL of Sterile Water for Injection [NDC 71127-2200-1] One 13 mm vial adapter with 5 micron filter 5 mg per vial Purple NDC 71127-5000-1 One 5 mg SEVENFACT single-dose vial [NDC 71127-5100-1] One pre-filled syringe containing 5.2 mL of Sterile Water for Injection [NDC 71127-5200-1] One 20 mm vial adapter with 5 micron filter The SEVENFACT vials are made of glass, closed with a bromobutyl rubber stopper (not made with natural rubber latex), and sealed with an aluminum cap. The pre-filled diluent syringes are made of glass, with a siliconized bromobutyl rubber plunger (not made with natural rubber latex). Storage and Handling Prior to reconstitution, the SEVENFACT kit should be stored at room temperature but can be stored between 36°F to 86°F (2°C to 30°C), protected from light in the product package. Do not freeze. After reconstitution, SEVENFACT should be stored at room temperature but can be stored between 36°F to 86°F (2°C to 30°C), for up to 4 hours. Do not freeze or store in syringes.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.