Ixinity
coagulation factor IX (recombinant) · Kit
Uses
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
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 baseline factor IX level is < 1% of normal): A peak of 70% is required in a 60 kg patient. The appropriate dose would be (60 kg × 70 IU/dL)/(0.98 IU/dL per IU/kg) = 4286 IU A dose of 4550 international units (IUs) of IXINITY administered to a 70 kg patient should be expected to result in a peak post-infusion factor IX increase of 4550 IU x (0.98 IU/dL per IU/kg)/(70 kg) = 64 IU/dL (approximately 64% of normal) Children (< 12 years of age): A lower recovery has been observed in pediatric patients (< 12 years, n=20). For an incremental recovery of 0.79 IU/dL per IU/kg (0.79% of normal), calculate the dose as follows: Dose (IU) = body weight (kg) x desired factor IX increase (% of normal or IU/dL) × 1.27 dL/kg Examples (assuming patient’s baseline factor IX level is < 1% of normal): A peak of 60% is required in a 20 kg patient. The appropriate dose would be (20 kg x 60 IU/dL)/(0.79 IU/dL per IU/kg) = 1519 IU A dose of 500 international units (IUs) of IXINITY administered to a 7 kg patient should be expected to result in a peak post-infusion factor IX increase of 500 IU x (0.79 IU/dL per IU/kg)/(7 kg) = 56 IU/dL (approximately 56% of normal) Monitor factor IX activity to ensure that the desired factor IX activity level has been achieved [see Warnings and Precautions (5.5) ]. Titrate doses using factor IX activity and pharmacokinetic parameters such as half-life and incremental recovery, as well as by taking the clinical situation into consideration, to adjust the dose and frequency of repeated infusions as appropriate. Factor IX activity measurements in the clinical laboratory may be affected by the type of activated partial thromboplastin time (aPTT) reagent or laboratory standard used [see Warnings and Precautions (5.5) ]. On-demand Treatment and Control of Bleeding Episodes and Perioperative Management of Bleeding Guides for dosing IXINITY in the on-demand treatment and control of bleeding episodes ( Table 1 ) and perioperative management ( Table 2 ) are provided in the tables below. Individual patients may vary in their response to factor IX and may demonstrate different levels of in vivo recovery and different half-lives. For surgical procedures, initiate treatment with IXINITY early enough pre-operatively to achieve and maintain the desired factor IX level before starting the procedure. Routine Prophylaxis For adolescents/ adults ≥ 12 years of age the recommended dose for previously treated patients (PTPs) is 40 to 70 IU/kg twice weekly. For children < 12 years of age the recommended dose for previously treated patients (PTPs) is 35 to 75 IU/kg twice weekly. Children (<12 years) have lower recovery, shorter half-life and higher clearance (based on per kg body weight) as compared to adolescents and adults. Adjust the dosing regimen (dose or frequency) based on the patient's clinical response. Adjust the dose based on the individual patient’s age, bleeding pattern, and physical activity.
Dosage forms and strengths
3 DOSAGE FORMS AND STRENGTHS IXINITY is available as a lyophilized white or almost white powder, in single-dose glass vials containing nominally 250, 500, 1000, 1500, 2000, or 3000 IU per vial. IXINITY is available as a lyophilized white or almost white powder, in single-dose glass vials containing nominally 250, 500, 1000, 1500, 2000, or 3000 international units (IU) per vial (3)
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 )
Warnings and precautions
Hypersensitivity reactions, including anaphylaxis has occurred. Should symptoms occur, discontinue IXINITY and administer appropriate treatment. Patients may also develop hypersensitivity to hamster (CHO) protein, which is present in trace amounts in the product ( 5.1 ) Development of neutralizing antibodies (inhibitors) to IXINITY may occur. If expected factor IX activity plasma levels are not attained, or if bleeding is not controlled with an appropriate dose, perform an assay that measures factor IX inhibitor concentration ( 5.2 ) Nephrotic syndrome has been reported following immune tolerance induction with factor IX products in hemophilia B patients with factor IX inhibitors ( 5.3 ) Thromboembolism has occurred with IXINITY use ( 5.4 ) 5.1 Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis, has occurred with IXINITY. Signs of allergic reactions, which can progress to anaphylaxis, include urticaria, angioedema, chest or throat tightness, hypotension, lethargy, nausea, vomiting, dysphagia, paresthesia, restlessness, wheezing and dyspnea. Immediately discontinue administration and initiate appropriate treatment if allergic or anaphylactic-type reactions occur. In case of severe allergic reactions, consider alternative hemostatic measures. There are literature reports of allergic reactions occurring in close temporal association with the development of factor IX inhibitors. IXINITY contains trace amounts of Chinese hamster ovary (CHO) proteins. Patients treated with this product may develop hypersensitivity to CHO proteins. 5.2 Neutralizing Antibodies Development of neutralizing antibodies (inhibitors) to IXINITY may occur. If expected factor IX activity plasma levels are not attained, or if bleeding is not controlled as expected with the calculated dose, perform an assay that measures factor IX inhibitor concentration [see Warnings and Precautions (5.5) ]. Patients with factor IX inhibitors are at an increased risk of severe hypersensitivity reactions or anaphylaxis if re-exposed to IXINITY. 5.3 Nephrotic Syndrome Nephrotic syndrome may occur with IXINITY. Nephrotic syndrome has been reported following attempted immune tolerance induction in hemophilia B patients with factor IX inhibitors and a history of allergic reactions. 5.4 Thromboembolism Thromboembolism has occurred with IXINITY use. One thrombotic event of deep vein thrombosis was reported in an adult female over 45 years of age from post-marketing experience. Because of the potential risk for thromboembolism with the use of factor IX products, monitor for early signs of thromboembolism and consumptive coagulopathy when administering IXINITY to patients with liver disease, fibrinolysis, peri-operative status, or risk for thromboembolic events or disseminated intravascular coagulation. 5.5 Monitoring Laboratory Tests Monitor patients for factor IX activity levels with the one-stage clotting assay to confirm that adequate factor IX levels have been achieved and maintained, when clinically indicated. Factor IX results can be affected by the type of aPTT reagent used [see Dosage and Administration (2.1) ]. Monitor patients for the development of inhibitors if expected factor IX activity plasma levels are not attained, or if bleeding is not controlled with the recommended dose of IXINITY. Assays used to determine if factor IX inhibitor is present should be titered in Bethesda Units (BUs).
Side effects
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.
Use in specific populations
Pediatric Use: The safety and effectiveness of IXINITY have been established in pediatric patients. Lower recovery, shorter half-life, and higher clearance (based on kg body weight) have been observed in children (< 12 years). Dose adjustment may be needed. ( 8.4 , 12.3 ) 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. 8.2 Lactation Risk Summary There is no information regarding the presence of IXINITY in human milk, the effect on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for IXINITY and any potential adverse effects on the breastfed infant from IXINITY or from the underlying maternal condition. 8.4 Pediatric Use The safety, efficacy, and pharmacokinetics of IXINITY have been evaluated in previously treated pediatric patients (PTP). Subjects received twice or once weekly prophylaxis treatment (four subjects were prescribed once a week treatment, 17 were prescribed twice a week treatment) with IXINITY for a mean of 158.7 exposure days [see Clinical Studies ( 14 ) ]. Compared to adolescents and adults (≥ 12 years old), children (< 12 years old) showed higher Factor IX body weight-adjusted clearance, shorter half-life, and lower recovery. Adjustment in dose or dosing frequency may be needed [see Dosage and Administration ( 2.1 ) and Clinical Pharmacology ( 12.3 ) ]. There were no inhibitors detected [see Clinical Pharmacology ( 12.6 ) ]. One patient in the pediatric study had an adverse reaction of hypersensitivity resulting in withdrawal from the study. No new safety concerns were identified in the pediatric trial [see Adverse Reactions ( 6.1 ) ]. 8.5 Geriatric Use Clinical studies of IXINITY did not include subjects aged 65 and over. It is not known whether elderly patients respond differently than younger patients. Individualize dose selection for elderly patients [see Dosage and Administration (2.1) ].
Pregnancy
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.
Pediatric use
8.4 Pediatric Use The safety, efficacy, and pharmacokinetics of IXINITY have been evaluated in previously treated pediatric patients (PTP). Subjects received twice or once weekly prophylaxis treatment (four subjects were prescribed once a week treatment, 17 were prescribed twice a week treatment) with IXINITY for a mean of 158.7 exposure days [see Clinical Studies ( 14 ) ]. Compared to adolescents and adults (≥ 12 years old), children (< 12 years old) showed higher Factor IX body weight-adjusted clearance, shorter half-life, and lower recovery. Adjustment in dose or dosing frequency may be needed [see Dosage and Administration ( 2.1 ) and Clinical Pharmacology ( 12.3 ) ]. There were no inhibitors detected [see Clinical Pharmacology ( 12.6 ) ]. One patient in the pediatric study had an adverse reaction of hypersensitivity resulting in withdrawal from the study. No new safety concerns were identified in the pediatric trial [see Adverse Reactions ( 6.1 ) ].
Geriatric use
8.5 Geriatric Use Clinical studies of IXINITY did not include subjects aged 65 and over. It is not known whether elderly patients respond differently than younger patients. Individualize dose selection for elderly patients [see Dosage and Administration (2.1) ].
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%
Mechanism of action
12.1 Mechanism of Action Hemophilia B is a sex-linked hereditary disorder of blood coagulation caused by a deficiency in factor IX and results in bleeding into joints, muscles or internal organs, either spontaneously or as a result of accidental or surgical trauma. Treatment with IXINITY replaces factor IX, thereby enabling a temporary correction of the factor deficiency and correction of the bleeding tendencies.
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.
Patient information
Advise patients to read the FDA-approved patient labeling ( Patient Information and Instructions for Use ). Inform patients of the early signs of hypersensitivity reactions (including hives, generalized urticaria, chest tightness, wheezing, and hypotension) and anaphylaxis. Instruct patients to discontinue use of the product and contact their physician if these symptoms occur. Advise patients to contact their physician or treatment facility for further treatment and/or assessment if they experience a lack of clinical response to factor IX replacement therapy, as in some cases this may be a manifestation of an inhibitor. Manufactured by: Medexus Pharma, Inc. Chicago, IL 60606 U.S. License No. 2220
Label text from the FDA structured product label by Medexus Pharma, Inc. (revised Apr 3, 2024). Long sections are shortened; the complete label is on DailyMed.
Ixinity NDC products (6)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 59137-282 | Kit | Medexus Pharma, Inc. | BLA |
| 59137-283 | Kit | Medexus Pharma, Inc. | BLA |
| 59137-284 | Kit | Medexus Pharma, Inc. | BLA |
| 59137-287 | Kit | Medexus Pharma, Inc. | BLA |
| 59137-288 | Kit | Medexus Pharma, Inc. | BLA |
| 59137-289 | Kit | Medexus Pharma, Inc. | BLA |
Frequently asked questions
What is Ixinity used for?
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 )…
What are the side effects of Ixinity?
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… See the full label for the complete list.
Who makes Ixinity?
Ixinity is listed by 1 labeler in the FDA NDC directory, including Medexus Pharma, Inc..