Ixinity Drug Information
Generic name: COAGULATION FACTOR IX (RECOMBINANT)
Uses of Ixinity
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. 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.
Dosage & Administration of Ixinity
| Initial Dose = body weight (kg) x desired factor IX increase (% of normal or IU/dL) | |
|---|---|
| × reciprocal of observed recovery (IU/kg per IU/dL) |
Side Effects of Ixinity
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%)
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.
Warnings & Cautions for Ixinity
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.
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. Patients with factor IX inhibitors are at an increased risk of severe hypersensitivity reactions or anaphylaxis if re-exposed to IXINITY.
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.
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.
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. 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).
Pregnancy Safety for Ixinity
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 of Ixinity
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. 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.
There were no inhibitors detected. 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.
Contraindications for Ixinity
is contraindicated in patients who have known hypersensitivity to IXINITY or its excipients, including hamster protein. Do not use in patients with known hypersensitivity to IXINITY or its excipients, including hamster protein
Clinical Studies of Ixinity
BU), a history of hypersensitivity reactions following exposure to factor IX-containing products
a known allergic reaction to hamster proteins, evidence of severe liver impairment, evidence of impaired renal function, CD4 count < 400 cells/mm 3, or any coagulation defect other than hemophilia B. In addition, there was a prospective, open-label, uncontrolled, multicenter substudy where 17 subjects (16 male, 1 female carrier) underwent surgeries (19 major procedures in males) receiving IXINITY for perioperative management; some of the surgery subjects also participated in the treatment trial. Of the 68 PTPs in the treatment group, subjects were primarily prescribed a routine prophylaxis (n = 58) or an on-demand regimen (n = 9); one subject was not assigned a regimen. Subjects were allowed to switch regimens during the course of the study.
As a result, 61 subjects were treated at some point with routine prophylaxis treatment and 12 were treated at some point with an on-demand regimen. Subjects in the routine prophylaxis therapy group received mean intravenous doses of 55 ±
IU/kg of
IXINITY twice weekly. Subjects in the on-demand therapy group received mean doses of 60 ±
IU/kg (median 59.3, interquartile range 49.9, 71.8) for bleeding episodes.
The mean number of exposure days (ED) was 138.2 (median 127.5), including 45 subjects with ≥ 100 ED and 55 subjects with ≥ 50 ED. Median duration on study for the on-demand group was 14.1 months (range 2.3-36.9). Annualized bleeding rates for PTPs ≥12 years of age in prophylaxis arm are summarized in Table 7. Table 7: Efficacy of Prophylaxis with IXINITY (N=61) for subjects ≥ 12 years of age a The lower quartile, or first quartile (Q1) is the value under which 25% of data points are found when arranged in increasing order. The upper quartile, or third quartile (Q3), is the value under which 75% of data points are found when arranged in increasing order. Total ABR Mean ± SD 3.55 ± 7.19 Median (Q1, Q3) a 1.52 (0;3.47) Spontaneous ABR Mean ± SD 1.07± 3.06 Median (Q1, Q3) a 0.00 (0;1.22) Subjects with zero bleeding episodes n (%) 19 (31.1%) PTP < 12 years of age The PK, safety and efficacy of IXINITY for treatment of hemophilia B was evaluated in a prospective multi-center, multi-country study of 21 previously treated patients (PTPs) (10 subjects < 6 years of age and 11 subjects 6 to < 12 years of age). PTP were defined as patients who were exposed to a factor IX containing product for ≥ 50 exposure days (ED). All subjects had severe to moderately severe (factor ≤ 2%). Subjects with history of hypersensitivity reactions following exposure to factor IX-containing products, a known allergic reaction to hamster proteins, evidence of severe liver impairment, evidence of impaired renal function, CD4 count < 400 cells/mm 3, or any coagulation defect other than hemophilia B, evidence of thrombotic disease, fibrinolysis, or disseminated intravascular coagulation (DIC) were excluded from the trial.
Subjects received IXINITY prophylaxis once to twice weekly, the recommended dose range was 35 – 75 IU/kg. Subjects < 6 years received a mean intravenous dose of 58 (45-72) ±
IU/kg and subjects 6 to < 12 received a mean intravenous dose
of 52 (46-60) ±
IU/kg. Twenty-one subjects completed the PK analysis, and 19 subjects completed a
minimum of 50 ED. The mean number of ED was 159 (median 163), including 16 subjects with ≥ 100 ED and 7 subjects with ≥ 200 ED. Annualized bleeding rates for PTPs <12 years of age are summarized in Table 8. Table 8: Efficacy of Prophylaxis with IXINITY (N=21) for subjects <12 years of age a The lower quartile, or first quartile (Q1) is the value under which 25% of data points are found when arranged in increasing order. The upper quartile, or third quartile (Q3), is the value under which 75% of data points are found when arranged in increasing order. Total ABR Mean ± SD 2.34 ± 4.23 Median (Q1, Q3) a 0.86 (0;1.96) Spontaneous ABR Mean ± SD 0.63 ± 1.26 Median (Q1, Q3) a 0.00 (0;0.85) Subjects with zero bleeding episodes n (%) 7 (33.3%) Control of Bleeding Episodes PTPs ≥ 12 years of age A total of 508 bleeding episodes were treated with IXINITY, of which 286 bleeds were recorded for subjects treated with the routine prophylaxis treatment regimen and 222 with the on-demand regimen.
Bleeding resolved in 360 episodes (70.9%) after a single infusion of IXINITY and in 66 (13.0%) episodes after two infusions. For 24 bleeding episodes (4.7%), five or more infusions were required; these 24 bleeding episodes were predominantly related to trauma, target joints, or muscle bleeds. Hemostatic efficacy to resolve a bleed was rated by subjects as excellent or good in 84% of treated bleeding episodes.
Excellent was defined as a dramatic response with abrupt pain relief and clear reduction in joint or hemorrhage site size, and good was defined as pain relief or reduction in hemorrhage size that may have required an additional infusion for resolution. PTP < 12 years of age There were 52 bleeding episodes; nine did not require treatment and resolved with IXINITY routine prophylaxis once or twice-weekly treatment. In 45 of 52 (86.5%) of the episodes, hemostasis was achieved with zero to two infusions.
For four bleeding episodes (7.7%) three infusions were required, two episodes (3.8%) four infusions were required, and one episode (1.9%) required five infusions for resolution. Hemostatic efficacy to resolve a bleed was rated by subjects as excellent or good in 41 (95%) of the 43 bleeding episodes that required treatment; two bleeding episodes did not have efficacy assessments. Excellent was defined as a dramatic response with abrupt pain relief and clear reduction in joint or bleeding site size and good was defined as pain relief or reduction in bleeding site size that may have required an additional infusion for resolution.
Perioperative Management The efficacy analysis of IXINITY in perioperative management included 19 major surgeries performed in 16 male PTPs between 12 and 56 years of age (female carrier not included in efficacy analysis). Efficacy of IXINITY for support of major surgery was based on the surgeon’s assessment of efficacy including: a) at the time of surgery as estimation of blood loss as ‘less than expected’, ‘expected’, or ‘more than expected’; and b) at 12 and 24 hours post-surgical assessments of hemostasis as ‘adequate’, ‘better than adequate’, or ‘poorly controlled’. Transfusion requirements to support surgery were also monitored. There were no transfusions required during the procedures. IXINITY was administered during major surgical procedures as bolus (n = 13) or continuous infusion (n = 6). IXINITY was rated as adequate or better in controlling hemostasis post-surgery as assessed by the surgeon when used in various procedures, including, knee arthroplasty (n = 8), elbow arthroplasty (n = 2), knee amputation (n = 1), percutaneous Achilles tendon lengthening (n = 1), open inguinal hernia repair (n = 1), tibiotalar fusion (n = 1), arthroscopic synovectomy (n = 2), and debridement (ankle, knee) (n = 3). In all instances, blood loss at surgery was ‘expected’ or ‘less than expected’ as assessed by the surgeon.
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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