Coagulation Factor Ix (Recombinant)
FDA Drug Information • Also known as: Benefix, Ixinity, Rixubis
- Brand Names
- Benefix, Ixinity, Rixubis
- Dosage Form
- KIT
- Product Type
- PLASMA DERIVATIVE
Description
11 DESCRIPTION IXINITY [coagulation factor IX (recombinant)] is a purified protein that has 415 amino acids. It has an amino acid sequence that is comparable to the Thr148 allelic form of plasma-derived factor IX. Coagulation factor IX (recombinant) is a single-chain glycoprotein with a molecular mass of about 55,000 Dalton that is secreted by a genetically engineered mammalian cell line derived from Chinese hamster ovary (CHO) cells. No human or animal proteins are added during any stage of manufacturing or formulation of IXINITY. The CHO cell line secretes recombinant factor IX into a defined cell culture medium that does not contain hormones. The recombinant factor IX is purified by a chromatography purification process. The process includes three validated steps for virus inactivation and removal, namely, solvent/detergent treatment, a chromatographic step, and nanofiltration. The process also includes a validated step to reduce the presence of CHO proteins in the final drug product. IXINITY is formulated as a sterile, nonpyrogenic lyophilized powder to be reconstituted with Sterile Water for Injection for intravenous administration. It does not contain any preservatives and is available in single-dose vials containing the labeled amount of factor IX activity, expressed in international units (IU). Each vial contains nominally 250, 500, 1000, 1500, 2000, or 3000 IU of recombinant coagulation factor IX. After reconstitution of the lyophilized powder, all dosage strengths yield a clear, colorless solution. The concentrations of excipients are: Excipient Concentration Histidine 10 mM Mannitol 3% Trehalose Dihydrate 1% Sodium Chloride 66 mM Polysorbate 80 0.0075%
What Is Coagulation Factor Ix (Recombinant) Used For?
1 INDICATIONS AND USAGE IXINITY, Coagulation Factor IX (Recombinant), is a human blood coagulation factor indicated in adults and children with hemophilia B for: On-demand treatment and control of bleeding episodes Perioperative management Routine prophylaxis to reduce the frequency of bleeding episodes IXINITY is not indicated for induction of immune tolerance in patients with hemophilia B [see Warnings and Precautions ( 5.3 ) ]. IXINITY, Coagulation Factor IX (Recombinant), is a human blood coagulation factor indicated in adults and children with hemophilia B for: On-demand treatment and control of bleeding episodes ( 1 ) Perioperative management ( 1 ) Routine prophylaxis to reduce the frequency of bleeding episodes ( 1 ) IXINITY is not indicated for induction of immune tolerance in patients with hemophilia B. ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION For intravenous use after reconstitution only. For intravenous use after reconstitution only. On-demand treatment and control of bleeding episodes and perioperative management of bleeding: Adolescents/Adults (≥ 12 years of age): One international unit (IU) of IXINITY per kg body weight increases the circulating activity of factor IX by 0.98 IU/dL. ( 2.1 ) Children (< 12 years of age): One international (IU) of IXINITY per kg body weight increases the circulating activity of factor IX by 0.79 IU/dL. ( 2.1 ) Initial dose: Required factor IX units (IU) = body weight (kg) x desired factor IX increase (% of normal or IU/dL) x reciprocal of observed recovery (IU/kg per IU/dL). ( 2.1 ) The maintenance dose depends on the type of bleed or surgery, the intensity of the hemostatic challenge, and number of days until adequate wound healing is achieved. ( 2.1 ) Routine prophylaxis: Adolescents/Adults (≥ 12 years of age): 40 to 70 IU/kg twice weekly. ( 2.1 ) Children (< 12 years of age): 35 to 75 IU/kg twice weekly. Adjust the dosing regimen (dose or frequency) based on the patient’s clinical response. ( 2.1 ) 2.1 Dose Each vial of IXINITY has the recombinant factor IX (rFIX) potency in international units (IU) stated on the vial. Dosage and duration of treatment for factor IX products depend on the severity of the factor IX deficiency, the location and extent of bleeding, the patient’s clinical condition, age, and pharmacokinetic parameters of factor IX, such as incremental recovery and half-life. Initial Dose Adolescents/Adults ≥ 12 years of age): Calculate the initial dose of IXINITY based on the empirical finding that one international unit (IU) of IXINITY per kg body weight increases the circulating level of factor IX by 0.98 international units/dL (IU/dL) of plasma in adults and children ≥ 12 years of age. Children (< 12 years of age): Calculate the initial dose of IXINITY based on the empirical finding that one international unit (IU) of IXINITY per kg body weight increases the circulating level of factor IX by 0.79 international units/dL (IU/dL) of plasma in children < 12 years of age. Initial Dose = body weight (kg) x desired factor IX increase (% of normal or IU/dL) × reciprocal of observed recovery (IU/kg per IU/dL) Incremental Recovery in Previously Treated Patients (PTPs) Base calculation of the dose on the patient’s individual incremental recovery using serial factor IX activity assays, to account for the wide range of inter-individual differences in incremental recovery and the type of aPTT reagent used for the assay. Titrate the dose based on the patient’s clinical response and individual pharmacokinetics, in particular incremental recovery and half-life. Adolescents/Adults (≥ 12 years of age): For an incremental recovery of 0.98 IU/dL per IU/kg (0.98% of normal), calculate the dose as follows: Dose (IU) = body weight (kg) x desired factor IX increase (% of normal or IU/dL) × 1.02 dL/kg Examples (assuming patient’s...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The most common adverse reaction (> 2%) reported in clinical trials was headache. The most common adverse reaction observed in > 2% of patients in clinical trials was headache ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Medexus Pharma, Inc. at 1-844-859-6675 or FDA at 1-800-FDA-1088 or 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 clinical practice. A total of 15 adverse reactions were reported following IXINITY administration among 7 of the 98 subjects who received at least one dose of IXINITY in trials of previously treated patients (PTPs), which included 11 subjects 12 - 18 years of age and 21 subjects < 12 years of age. A total of 12,952 infusions of IXINITY were administered to the 98 subjects. The adverse reactions that were assessed as probably or possibly related to study drug are provided in the table below. Table 3 Summary of Adverse Reactions MedDRA Standard System Organ Class Adverse Reaction Number of Events Number of Subjects (n = 98) (%) Congenital, familial and genetic disorders Hemophilia (i.e., lack of efficacy) 1 1 (1.0%) General disorders and administration site conditions Asthenia 1 1 (1.0%) Injection site discomfort 1 1 (1.0%) Immune System Disorders Hypersensitivity 1 1 (1.0%) Infections and infestations Influenza 1 1 (1.0%) Nervous system disorders Headache 5 2 (2.0%) Dysgeusia 1 1 (1.0%) Lethargy 1 1 (1.0%) Psychiatric disorders Apathy 1 1 (1.0%) Depression 1 1 (1.0%) Skin and subcutaneous tissue disorders Rash pruritic 1 1 (1.0%) 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of IXINITY. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune System Disorders: Anaphylaxis Vascular Disorders: Deep vein thrombosis The following class adverse reactions have been seen with another recombinant factor IX: inadequate factor IX recovery, inhibitor development, angioedema, hypotension, and thrombosis.
Contraindications
4 CONTRAINDICATIONS IXINITY is contraindicated in patients who have known hypersensitivity to IXINITY or its excipients, including hamster protein [see Warnings and Precautions (5.1) ]. Do not use in patients with known hypersensitivity to IXINITY or its excipients, including hamster protein ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are no data with IXINITY use in pregnant women to inform a drug-associated risk. Animal reproduction studies have not been conducted with IXINITY. In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING IXINITY is supplied as a lyophilized powder in single-dose glass vials containing the labeled amount of factor IX activity, expressed in international units (IU). The actual factor IX activity in IU is stated on the label of each vial. Kits include one single-dose vial (containing nominally 250, 500, 1000, 1500, 2000, or 3000 IU per vial), a 10 mL syringe pre-filled with 5 mL of Sterile Water for Injection with plunger rod attached, and a vial adapter with filter. None of the kit components are made with natural rubber latex. Color Code Nominal Strength Kit NDC Number Yellow 250 IU 59137-287-05 Blue 500 IU 59137-282-05 Green 1000 IU 59137-283-05 Orange 1500 IU 59137-284-05 Red 2000 IU 59137-288-05 Brown 3000 IU 59137-289-05 250 IU strength only; store at 2 to 8°C (36 to 46°F). 500, 1000, 1500, 2000, and 3000 IU strengths: store at 2 to 25°C (36 to 77°F). Do not freeze. Keep the vial in the carton and protect from light. Infuse reconstituted solution immediately or within 3 hours of storage at room temperature after reconstitution. Do not refrigerate after reconstitution.
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.