Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Idelvion: 250 units (1 ea); 500 units (1 ea); 1000 units (1 ea); 2000 units (1 ea) [contains hamster protein, polysorbate 80]
Solution Reconstituted, Intravenous [preservative free]:
Idelvion: 3500 units (1 ea) [contains hamster protein, polysorbate 80]
Pharmacology
Mechanism of Action
Factor IX (recombinant [albumin fusion protein]) is a recombinant protein that temporarily replaces the missing coagulation factor IX needed for effective hemostasis in patients with hemophilia B. Factor IX (recombinant [albumin fusion protein]) is comprised of genetically fused recombinant coagulation factor IX and recombinant albumin. Fusion with recombinant albumin extends the half-life of factor IX.
Pharmacokinetics/Pharmacodynamics
Distribution
Adults: Vss: 0.86 to 1.2 dL/kg; Children and Adolescents <18 years: 1.16 to 1.42 dL/kg
Half-Life Elimination
Adults: 104 to 118 hours; Infants, Children, and Adolescents <18 years: 87 to 93 hours
Use in Specific Populations
Special Populations: Children
Compared to adults, incremental rIX-FP recovery appeared to be slightly lower and body weight-adjusted clearance appeared to be higher. Children may have higher Factor IX body weight-adjusted clearance, shorter half-life, and lower recovery. Higher dose per kilogram body weight or more frequent dosing may be needed in these patients.
Use: Labeled Indications
Hemophilia B (congenital factor IX deficiency): Prevention and on-demand control of bleeding episodes in adults and children; perioperative management of bleeding in adults and children; routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children
Limitations of use: Not indicated for immune tolerance induction in patients with hemophilia B.
Contraindications
Life-threatening hypersensitivity to factor IX (recombinant [albumin fusion protein]) or any component of the formulation including hamster proteins
Dosage and Administration
Dosing: Adult
Note: Dose and duration of treatment depends on the severity of factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition, age, and recovery of factor IX. Adjust dosing regimen based on individual response.
Hemophilia B (congenital factor IX deficiency): The calculation of the required dose is based on 1 unit/kg body weight is expected to increase the factor IX circulating level by 1.3 units/dL in adults. The required dose is determined by the following formula:
Number of factor IX units required = patient weight (in kg) x desired factor IX level increase (as % or units/dL) x reciprocal of recovery (as units/kg per units/dL)
On-demand control and prevention of bleeding episodes: IV:
|
Type of bleeding episode |
Required circulating factor IX activity |
Dosing frequency |
Duration of therapy |
|---|---|---|---|
|
Minor or moderate (uncomplicated hemarthrosis, muscle bleeding [except iliopsoas] or oral bleeding) |
30 to 60 units/dL |
48 to 72 hours |
At least 1 day, until bleeding stops and healing is achieved. Single dose should be sufficient for majority of bleeds. |
|
Major (life or limb threatening hemorrhage, deep muscle bleeding, including iliopsoas, intracranial, retropharyngeal) |
60 to 100 units/dL |
48 to 72 hours |
7 to 14 days, or until bleeding stops and healing is achieved. Maintenance dose weekly. |
Perioperative management of bleeding: IV:
|
Type of bleeding surgery |
Required circulating factor IX activity |
Dosing frequency |
Duration of therapy |
|---|---|---|---|
|
Minor (including uncomplicated tooth extraction) |
50 to 80 units/dL |
48 to 72 hours |
At least 1 day, until bleeding stops and healing is achieved. Single dose should be sufficient for majority of minor surgeries. |
|
Major (including intracranial, pharyngeal, retropharyngeal, retroperitoneal) |
60 to 100 units/dL |
48 to 72 hours |
7 to 14 days, or until bleeding stops and healing is achieved. Repeat dose every 48 to 72 hours for the first week or until healing is achieved. Maintenance dose 1 to 2 times per week |
Routine prophylaxis: IV: 25 to 40 units/kg once every 7 days; if well controlled may switch to 50 to 75 units/kg once every 14 days.
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Note: Dose and duration of treatment depends on the severity of factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition, age, and recovery of factor IX. Adjust dosing regimen based on individual response.
Hemophilia B (congenital factor IX deficiency): The calculation of the required dose is based on 1 unit/kg body weight is expected to increase the factor IX circulating level by 1 units/dL in infants and children <12 years and by 1.3 units/dL in Children ≥12 years and Adolescents. The required dose is determined by the following formula:
Number of factor IX units required = patient weight (in kg) x desired factor IX level increase (as % or units/dL) x reciprocal of recovery (as units/kg per units/dL)
On-demand control and prevention of bleeding episodes: Infants, Children, and Adolescents: IV: Refer to adult dosing.
Perioperative management of bleeding: Infants, Children, and Adolescents: IV: Refer to adult dosing.
Routine prophylaxis:
Infants and Children <12 years: IV: 40 to 55 units/kg once every 7 days
Children ≥12 years and Adolescents: IV: Refer to adult dosing.
Reconstitution
Use aseptic technique during the reconstitution procedure. Use the diluent (sterile water for injection) and transfer device provided. Allow factor IX product and diluent to reach room temperature prior to reconstitution. See prescribing information for detailed reconstitution instructions. Dispense in a syringe for administration.
Administration
IV: For IV injection only. Do not use if particulate matter or discoloration is observed. Adjust infusion rate to comfort level of the patient, not exceeding 10 mL/minute. Administer at room temperature and within 4 hours of reconstitution.
Storage
Store in refrigerator or at room temperature from 2°C to 25°C (36°F to 77°F). Do not freeze; store in package to protect from light. Reconstituted solution should be used immediately or within 4 hours of preparation.
Drug Interactions
There are no known significant interactions.
Adverse Reactions
Central nervous system: Headache (≤2%)
<1%, postmarketing, and/or case reports: Dizziness, eczema, hypersensitivity reaction, infusion related reaction, nephrotic syndrome, skin rash
Warnings/Precautions
Concerns related to adverse effects:
- Antibody formation: Neutralizing antibodies (inhibitors) to factor IX may develop; monitor for development of antibodies with lab tests and clinical observation. Perform assay to measure factor IX inhibitor concentration if expected plasma factor IX activity levels are not attained or if bleeding is not controlled at an appropriate dose. Patients with factor IX inhibitors are at increased risk for severe hypersensitivity reactions or anaphylaxis upon re-exposure. Evaluate patients experiencing allergic reactions for the presence of an inhibitor. Monitor patients with inhibitors for signs/symptoms of acute hypersensitivity, particularly in the early phases of exposure.
- Hypersensitivity: Hypersensitivity reactions (including anaphylaxis) may occur; early signs include angioedema, chest tightness, hypotension, urticarial (generalized) wheezing, and dyspnea. Discontinue immediately (and manage appropriately) if symptoms of hypersensitivity occur. Contains trace amounts of Chinese hamster ovary proteins; hypersensitivity to these proteins may develop.
- Nephrotic syndrome: Nephrotic syndrome has been reported following attempted immune tolerance induction in hemophilia B patient with factor IX inhibitors and a history of allergic reactions. Safety and efficacy in this situation have not been established.
- Thromboembolic events: Thromboembolism (eg, pulmonary embolism, venous/arterial thrombosis) may occur. Monitor for early signs of thromboembolism and coagulopathy in patients with hepatic disease, fibrinolysis, perioperative status, or risk factors for thromboembolic events or disseminated intravascular coagulation.
Dosage form specific issues:
- Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling.
Monitoring Parameters
Monitor factor IX levels by the one-stage clotting assay to confirm adequate factor IX levels are achieved/maintained (measure 15 minutes after infusion to verify calculated doses (WFH [Srivastava 2013]), aPTT, BP, HR, signs of hypersensitivity reactions, DIC, and thrombosis; screen for factor IX inhibitors if the patient experiences hypersensitivity reaction or when patient is to undergo surgery, if suboptimal response to treatment occurs, if patient is being intensively treated for >5 days within 4 weeks of the last infusion, or at the following intervals (WFH [Srivastava 2013]):
Children: Screen for inhibitors every 5 exposure days until 20 exposure days, every 10 exposure days between 21 to 50 exposure days, and at a minimum of twice a year until 150 exposure days is reached.
Adults (with >150 exposure days apart from a 6 to 12 monthly review): Screen for inhibitors when suboptimal response occurs.
Pregnancy
Pregnancy Considerations
Pregnant hemophilia B carriers may have an increased bleeding risk following abortion, invasive procedures, miscarriage, and delivery; close surveillance is recommended. Factor IX levels should be monitored at the first antenatal visit, once or twice during the third trimester, prior to surgical or invasive procedures, and at delivery. Although factor IX levels remain stable during pregnancy, factor IX replacement is recommended if concentrations are <0.5 IU/mL and any of the following occur: need for invasive procedures (including delivery), spontaneous miscarriage, insertion and removal of epidural catheters, or active bleeding. Hemostatic factor IX concentrations should be maintained for at least 3 to 5 days following invasive procedures or postpartum. If replacement with a factor IX concentrate is indicated to increase factor IX during pregnancy, a recombinant product is preferred (NHF 2017; RCOG [Pavord 2017]; WFH [Srivastava 2013]).
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache. Have patient report immediately to prescriber signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), signs of blood clots (numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; chest pain; shortness of breath; fast heartbeat; or coughing up blood), signs of kidney problems (unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain), dizziness, passing out, or confusion (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
