Idelvion (factor IX recombinant,albumin fusion protein)
Factor IX Intravenous Vial (Ea)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Factor IX (recombinant), albumin fusion protein (rIX-FP) is a biosynthetic (recombinant DNA origin) preparation of blood coagulation factor IX genetically fused to recombinant albumin via a short, cleavable peptide derived from the activation peptide of endogenous factor IX.
Factor IX (recombinant), albumin fusion protein is a biosynthetic (recombinant DNA-origin) preparation of blood coagulation factor IX that consists of the human coagulation factor IX sequence genetically fused to recombinant albumin via a short, cleavable peptide derived from the activation peptide of endogenous factor IX. The peptide sequence is cleaved from the fusion protein by enzymes such as factor XIa or factor VIIa/tissue factor, which are the same enzymes that activate factor IX during the clotting cascade; thus, when factor IX is activated, the albumin portion of the fusion protein is released. Albumin is protected from degradation by pH-dependent binding to the neonatal Fc receptor (also present on many adult cells) and as a result, factor IX (recombinant), albumin fusion protein has an increased circulating half-life compared with other factor IX (recombinant) preparations.
The factor IX portion of factor IX (recombinant), albumin fusion protein is similar in structure and function to endogenous factor IX.
Factor IX is essential for blood clotting and maintenance of hemostasis. Patients with hemophilia B have deficient levels of endogenous factor IX, resulting in a hemorrhagic tendency and clinical manifestations such as bleeding into soft tissues, muscles, joints, and internal organs. Clinical severity and frequency of bleeding in patients with hemophilia B correlate with the degree of deficiency of factor IX activity.
Patients with mild hemophilia B generally have factor IX activity levels exceeding 5% of normal, while those with moderate or severe disease generally have factor IX levels of 1-5% or less than 1%, respectively, of normal. Administration of factor IX (recombinant), albumin fusion protein to patients with hemophilia B increases plasma levels of factor IX and temporarily corrects the coagulation defect.
Factor IX (recombinant), albumin fusion protein is produced by recombinant DNA technology in a Chinese hamster ovary (CHO) cell line and undergoes several purification and viral inactivating/removal processes (e.g., solvent/detergent treatment, filtration). The CHO cell line used to produce factor IX (recombinant), albumin fusion protein secretes recombinant factor IX into a defined cell culture medium that does not contain hormones and is manufactured without the use of animal or human proteins. Compared with plasma-derived factor IX, recombinant preparations of factor IX are associated with a substantially reduced risk of transmission of bloodborne human viruses (e.g., human immunodeficiency virus (HIV), hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV)).
In pharmacokinetic studies, adults (18 years of age or older) received single doses (25, 50, or 75 units/kg) of factor IX (recombinant), albumin fusion protein and blood samples were collected prior to dosing and up to 14 days after dosing. Compared with adults, incremental recovery was lower and body weight-adjusted clearance was higher in children or adolescents (0 to less than 18 years of age) who received a single 50-unit/kg dose of factor IX (recombinant), albumin fusion protein. In adults receiving a single 50-unit/kg dose, the half-life of the drug was 104 hours and the average time to decline to 1% of factor IX activity was approximately 23 days.
In clinical trials, factor IX (recombinant), albumin fusion protein has demonstrated approximately a threefold to fivefold prolongation of the half-life of factor IX activity in circulation when compared with the half-lives of unmodified factor IX preparations.
USES: This medication is used to prevent or control bleeding in people with little or no factor IX (due to hemophilia B, Christmas disease). Factor IX is a protein (clotting factor) in the blood that works with other clotting factors to help the blood clot and stop bleeding. People with little or no factor IX are at risk for bleeding longer after an injury/surgery or bleeding suddenly (often in the joints/muscle) without an obvious cause.
This medication should not be used to treat other types of factor deficiencies (such as factors II, VII, VIII, X) or factor problems (such as inhibitor to factor XIII), to reverse the effects of "blood thinners" (such as warfarin), or to treat bleeding from low levels of liver-dependent clotting factors (due to liver problems).
Generic name: factor IX recombinant,albumin fusion protein
Pronunciation: (FACK-ter nine)
Drug class: Factor IX
Therapeutic class: Hematological Agents
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Idelvion
Indications
The following indications are listed for Idelvion:
- Hemophilia B
Also known as: Christmas Disease, Factor Ix Deficiency, Factor Ix Dysfunction, Plasma Thromboplastin Component Deficiency, Ptc Deficiency.
Dosing
Dosage (potency) of factor IX (recombinant), albumin fusion protein is expressed in terms of international units (IU, units) of factor IX activity. Potency is determined by an activated partial thromboplastin time (aPTT)-based one-stage clotting assay calibrated against a standard established by the World Health Organization (WHO). Administration of 1 unit/kg of factor IX (recombinant), albumin fusion protein increases circulating levels of factor IX by 1.3 units/dL in patients 12 years of age and older and by 1 unit/dL in patients younger than 12 years of age.
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Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
Factor Ix; Anti-Inhibitor Coagulant Conc/Antifibrinolytics
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Concurrent use may result in additive or synergistic effects on the coagulation pathways.(1-3)
CLINICAL EFFECTS: Concurrent use may result in thrombosis.(1-3)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The manufacturer of aminocaproic acid states that aminocaproic acid should not be administered concomitantly with Factor IX Complex concentrates or Anti-inhibitor Coagulant concentrates.(1) The US manufacturer of tranexamic acid states that concomitant use with Factor IX Complex concentrates or with Anti-inhibitor Coagulant concentrates should be avoided.(2,3) The Japanese manufacturer of tranexamic acid recommends caution when coadministered with drugs such as coagulation factor agents as coagulation may be further activated at sites with enhanced local fibrinolysis.(4) Concurrent use may be warranted in select patients with hemophilia A or hemophilia B or in select major trauma scenarios. Monitor patients closely for signs of thrombosis, disseminated intravascular coagulation, and hypercoagulability if concurrent use is deemed necessary.(5-13)
DISCUSSION: There is very limited data on the risk of thrombosis with combination therapy. In a study, eight hemophilia B patients undergoing dental extraction procedures received combination therapy with aminocaproic acid or tranexamic acid and monoclonal antibody purified factor IX for bleeding prophylaxis. All patients achieved hemostasis without clinical evidence of thrombosis as well as no changes were seen in hemoglobin, hematocrit, or in markers of hemostatic system activation.(5) In a study, seven hemophilia A patients with inhibitors and one with acquired hemophilia patient received activated prothrombin complex concentrate (APCC) and tranexamic acid for management of bleeding episodes and prevention of hemorrhage during surgery. Hemostatic outcomes were rated excellent or good in 10 out of 11 (91%) treatment episodes. No episodes of thrombosis or disseminated intravascular coagulation occurred during treatment.(6) A study in six hemophilia A patients and five healthy volunteers evaluated the use of tranexamic acid as an adjunct to APCC to control bleeding. Patients who received tranexamic acid had a significant increase in maximum clot firmness compared to healthy controls. No clinical or laboratory signs of thromboembolic events, disseminated intravascular coagulation, or hypercoagulability were observed.(7) In a retrospective cohort of 76 patients who received PCC for bleeding not caused by anticoagulation, some patients received additional hemostatic agents (protamine (59%), desmopressin (43%), and tranexamic acid (42%). Eight patients (11%) suffered thromboembolic complications but this was not stratified by the hemostatic agent.(8) In a prospective case crossover study, five healthy volunteers and six hemophilia patients with inhibitors received tranexamic acid with single-dose activated PCC or with recombinant activated factor VII. There were no thromboembolic events during the study.(9) In a double-blind, randomized, placebo-controlled superiority trial to investigate the efficacy and safety of 4-factor prothrombin complex concentrate (4F-PCC) administration in trauma patients at risk of massive transfusion, a significantly higher risk of thromboembolic events occurred in the 4F-PCC group compared to the placebo group (35% vs 24%; relative risk 1.48 [95% CI, 1.04-2.10]). This was observed despite more frequent use of tranexamic acid in the placebo group (86% vs 76%).(10) Case reports reviewed the use of recombinant factor VIIa and FEIBA in 4 patients with severe hemophilia with inhibitors who underwent major surgery. The patients were also treated with tranexamic acid. Non-surgical bleeding was encountered in 4 of 8 surgical procedures. The overall outcome was good for all procedures.(11) In a retrospective cohort of 112 ambulatory tooth extractions in 23 hemophilia patients using a coagulation factor replacement therapy in combination with tranexamic acid, only one episode of mild postoperative bleeding occurred after seven days in a patient who did not have good treatment compliance.(12) In a prospective study evaluating the use of initial hemoglobin levels as a guideline for the initial treatment of clotting disorders in multiple trauma patients, 25 patients received a combination of hemostatic agents (fibrinogen (100%), PCC (96%), desmopressin (56%), tranexamic acid (52%), and factor VIIa (44%). Of the 25 patients treated, 16 (64%) survived. Two patients (8%) suffered thromboembolic complications but this was not stratified by the hemostatic agent. One patient survived after developing a grade II pulmonary embolism caused by deep leg vein trombosis and one patient died from multi-organ failure after developing multiple small vessel thrombosis.(13)
There are no moderate interactions for this drug.
Contraindications
Known history of life-threatening hypersensitivity to factor IX (recombinant), albumin fusion protein or any ingredient in the formulation (including hamster proteins).
There are no contraindication contraindications for this drug.
- Disseminated intravascular coagulation
- Thromboembolic disorder
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse effect observed in more than 1% of patients receiving factor IX (recombinant), albumin fusion protein in clinical trials was headache.
More Frequent
- Acute myocardial infarction
- Disseminated intravascular coagulation
- Pulmonary thromboembolism
- Thromboembolic disorder
- Thrombotic disorder
Less Frequent
- Anaphylaxis
- Urinary tract obstructive uropathy
Rare or Very Rare
- Hypersensitivity drug reaction
- Hypotension
- Renal colic
Less Frequent
- Chills
- Injection site sequelae
- Nausea
- Oral paresthesia
Rare or Very Rare
- Anorexia
- Dizziness
- Dysgeusia
- Fatigue
- Fever
- Halitosis
- Headache disorder
- Hematuria
- Lethargy
- Palpitations
- Paresthesia
- Urticaria
Precautions
No enhanced messaging available.
Safety, efficacy, and pharmacokinetics of factor IX (recombinant), albumin fusion protein have been evaluated in 32 pediatric patients. Prophylactic administration of factor IX (recombinant), albumin fusion protein was successful in prevention of spontaneous bleeding episodes and there were no differences in the safety profile in pediatric patients as compared with adults.
Compared with adults, pediatric patients may have higher body weight-adjusted clearance, shorter half-life, and lower factor IX recovery; higher doses or more frequent dosing may be required. (See Dosage and Administration: Dosage.)
Animal reproduction studies have not been performed with factor IX (recombinant), albumin fusion protein. It is not known whether the drug can cause fetal harm or affect reproduction capacity when administered to a pregnant woman. Factor IX (recombinant), albumin fusion protein should be used during pregnancy only when clearly needed.
It is not known whether factor IX (recombinant), albumin fusion protein is distributed into human milk. Because many drugs are distributed into milk, the drug should be used with caution in nursing women.
Clinical studies of factor IX (recombinant), albumin fusion protein did not include any patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients.
ICD codes
| Code | Type | Description |
|---|---|---|
| Hemophilia B | ||
| D67 | ICD10CM | Hereditary factor IX deficiency |
ICD code information from First Databank (FDB).
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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