Version May 2024
Hemophilia B (congenital factor IX deficiency): Individualize dosage based on clinical response and factor IX activity evaluated at baseline and at regular intervals during treatment. In general, administration of factor IX (recombinant [albumin fusion protein]) 1 unit/kg will increase circulating factor IX levels by 1 units/dL in infants and children <12 years and by 1.3 units/dL in children ≥12 years and adolescents.
General dosing recommendations: Note: Dose and duration of treatment depends on the severity of factor IX deficiency, location and extent of bleeding, and the patient's clinical condition, age, and recovery of factor IX. Adjust dosing regimen based on individual response.
Infants, Children, and Adolescents: IV:
Formula for units required to raise blood level:
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)
Reciprocal of recovery (as units/kg per units/dL):
Infants and Children <12 years: 1
Children ≥12 years and Adolescents: ~0.8
On-demand control and prevention of bleeding episodes: Infants, Children, and Adolescents: IV:
|
Type of Bleeding |
Desired Factor IX Level |
Frequency |
Duration |
|---|---|---|---|
|
Minor or moderate bleeding (eg, 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 bleeding (eg, 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: Infants, Children, and Adolescents: IV:
|
Type of Surgery |
Desired Factor IX Level |
Frequency |
Duration |
|---|---|---|---|
|
Minor Surgery (including uncomplicated tooth extraction) |
50 to 80 units/dL |
48 to 72 hours |
At least 1 day or until bleeding stops and healing is achieved. Single dose should be sufficient for majority of minor surgeries. |
|
Major Surgery (including intracranial, pharyngeal, retropharyngeal, retroperitoneal) |
60 to 100 units/dL (initial level) |
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:
Infants and Children <12 years: IV: 40 to 55 units/kg/dose once every 7 days.
Children ≥12 years and Adolescents: IV: 25 to 40 units/kg/dose once every 7 days; if well controlled, may switch to 50 to 75 units/kg/dose once every 14 days.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution in patients with hepatic disease.
(For additional information see "Factor IX, recombinant human with albumin fusion: Drug information")
Hemophilia B, without inhibitors:
Note: Contains only factor IX. Therefore, NOT INDICATED for replacement therapy of other clotting factors besides factor IX, hemophilia A patients with inhibitors to factor VIII, reversal of anticoagulation due to vitamin K antagonists or other anticoagulants, or bleeding due to low levels of liver-dependent clotting factors.
Treatment and control of bleeding episodes or perioperative management:
Intermittent IV bolus dosing: IV: Utilize steps 1 to 4 to determine intermittent bolus dosing strategy. Individualize dosage based on coagulation studies performed prior to treatment and at regular intervals during treatment.
Step 1: Identify product-specific in vivo recovery (IVR) for dosing calculations (Note: IVR indicates the expected increase in factor IX level, which occurs with 1 unit/kg of factor IX product administration):
Idelvion IVR: 1.3.
Step 2: Determine desired factor IX peak level and anticipated duration of therapy based on the World Federation of Hemophilia (WFH) treatment recommendations; see table. Selection of the lower-dose practice pattern requires closer observation with the potential for requiring escalation to higher doses based on clinical response.
|
Type of hemorrhage or surgery |
Lower dose practice pattern |
Higher dose practice pattern | ||
|---|---|---|---|---|
|
Desired peak factor IX level (units/dL) |
Treatment duration (days) |
Desired peak factor IX level (units/dL) |
Treatment duration (days) | |
|
a WFH = World Hemophilia Federation; (WFH [Srivastava 2020]). b May be longer if response is inadequate. c Sometimes longer as secondary prophylaxis during physical therapy. d A single dose may be sufficient for some joint bleeds; determine need for additional doses based on clinical response. | ||||
|
Joint |
10 to 20 |
1 to 2b,d |
40 to 60 |
1 to 2b,d |
|
Superficial muscle/no neurovascular compromise (except iliopsoas) |
10 to 20 |
2 to 3b |
40 to 60 |
2 to 3b |
|
Iliopsoas or deep muscle with neurovascular injury or substantial blood loss | ||||
|
Initial |
15 to 30 |
1 to 2 |
60 to 80 |
1 to 2 |
|
Maintenance |
10 to 20 |
3 to 5c |
30 to 60 |
3 to 5c |
|
Intracranial | ||||
|
Initial |
50 to 80 |
1 to 3 |
60 to 80 |
1 to 7 |
|
Maintenance |
30 to 50 |
4 to 7 |
30 |
8 to 21 |
|
20 to 40 |
8 to 14 |
- |
- | |
|
Throat and neck | ||||
|
Initial |
30 to 50 |
1 to 3 |
60 to 80 |
1 to 7 |
|
Maintenance |
10 to 20 |
4 to 7 |
30 |
8 to 14 |
|
GI | ||||
|
Initial |
30 to 50 |
1 to 3 |
60 to 80 |
7 to 14 |
|
Maintenance |
10 to 20 |
4 to 7 |
30 |
- |
|
Renal |
15 to 30 |
3 to 5 |
40 |
3 to 5 |
|
Deep laceration |
15 to 30 |
5 to 7 |
40 |
5 to 7 |
|
Surgery (major) | ||||
|
Pre-op |
50 to 70 |
- |
60 to 80 |
- |
|
Post-op |
30 to 40 |
1 to 3 |
40 to 60 |
1 to 3 |
|
20 to 30 |
4 to 6 |
30 to 50 |
4 to 6 | |
|
10 to 20 |
7 to 14 |
20 to 40 |
7 to 14 | |
|
Surgery (minor) | ||||
|
Pre-op |
40 to 80 |
- |
50 to 80 |
- |
|
Post-op |
20 to 50 |
1 to 5 |
30 to 80 |
1 to 5 |
Step 3: Calculate dose using IVR from step 1, desired peak factor IX level from step 2, and the following equation:
Factor IX units required = ([desired peak factor IX level − patient's baseline factor IX level] × body weight [kg])/IVR
(Note: Factor IX units are in units/dL.)
Example (Idelvion) for 50 kg patient with desired peak factor IX level of 35 units/dL, baseline factor IX level of 5 units/dL, IVR = 1.3:
Factor IX units required = ([35 units/dL − 5 units/dL] × 50 kg) ⁄ 1.3 = 1,154 units factor IX
Step 4: Determine need for repeat dosing based on manufacturer’s recommended frequency of repeat dosing. Note : Frequency of administration must also take into consideration subsequent factor IX activity measurements and clinical response.
|
Product |
Bleeding event |
Surgery | |||
|---|---|---|---|---|---|
|
Minor severity |
Moderate severity |
Major severity |
Minor bleeding risk |
Major bleeding risk | |
|
Idelvion |
Every 48 to 72 hours |
Every 48 to 72 hours |
Every 48 to 72 hours |
Every 48 to 72 hours |
Every 48 to 72 hours |
Routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with moderate/severe hemophilia B without inhibitors:
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 should be tailored to ensure trough factor IX levels of ≥1% and preferably ≥3 % to 5% are achieved, but prophylaxis targets should be tailored to individual level of activity, lifestyle, and pharmacokinetics. Dose escalation should be considered for patients adherent to prescribed prophylaxis but still experiencing breakthrough bleeding events (WFH [Srivastava 2020]).
There are no dosage adjustments provided in the manufacturers labeling.
There are no dosage adjustments provided in the manufacturers labeling; use with caution in patients with hepatic disease.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in previously treated patients.
1% to 10%: Nervous system: Dizziness (2%), headache (2%)
<1%:
Dermatologic: Eczema, skin rash
Hypersensitivity: Hypersensitivity reaction
Postmarketing:
Hematologic & oncologic: Factor IX inhibitor in hemophilia B
Immunologic: Antibody development (neutralizing)
Life-threatening hypersensitivity to factor IX (recombinant [albumin fusion protein]) or any component of the formulation including hamster proteins
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.
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]
No
Solution (reconstituted) (Idelvion Intravenous)
250 unit (Price provided is per AHF Unit): $6.22
500 unit (Price provided is per AHF Unit): $6.22
1000 unit (Price provided is per AHF Unit): $6.22
2000 unit (Price provided is per AHF Unit): $6.22
3500 unit (Price provided is per AHF Unit): $6.22
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Idelvion: 1000 units (1 ea) [contains hamster protein, polysorbate 80]
Parenteral: IV: For IV administration only. Do not use if particulate matter or discoloration is observed. Administer at room temperature and within 4 hours of reconstitution through a separate line; do not mix with other drugs. Adjust infusion rate to comfort level of the patient, not exceeding 10 mL/minute. With patients who have had allergic reactions during factor IX infusion, administration of antihistamine prior to infusion may be necessary (WFH [Srivastava 2020]).
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.
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.
On-demand treatment and control of bleeding episodes in patients with hemophilia B (congenital factor IX deficiency); perioperative management of bleeding in patients with hemophilia B; routine prophylaxis to reduce the frequency of bleeding episodes in patients with hemophilia B (All indications: FDA approved in children and adults).
Limitations of use: Not indicated for immune tolerance induction in patients with hemophilia B.
Factor IX (Recombinant [albumin fusion protein]) may be confused with other factor IX products
None known.
There are no known significant interactions.
Pregnant carriers of hemophilia B may have an increased bleeding risk following abortion, invasive procedures, spontaneous miscarriage, termination of pregnancy, 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 <50 units/dL 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 2020]).
Monitor factor IX levels by the one-stage clotting assay (measure 15 to 30 minutes after infusion to verify calculated doses (WFH [Srivastava 2020]), signs of hypersensitivity reactions, disseminated intravascular coagulation, 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, or after recurrent bleeds despite adequate factor IX replacement; all patients should have factor IX inhibitors screened every 6 to 12 months after therapy is initiated and then annually (WFH [Srivastava 2020]).
Classification of hemophilia (WFH [Srivastava 2020]):
Severe: Factor level <1% of normal.
Moderate: Factor level 1% to 5% of normal.
Mild: Factor level 5% to <40% of normal.
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.
Distribution: Vss:
Pediatric patients:
0 to <6 years: 1.42 dL/kg.
6 to <12 years: 1.32 dL/kg.
12 to <18 years: 1.16 dL/kg.
Adults: 0.86 to 1.2 dL/kg.
Half-life elimination:
Pediatric patients:
0 to <6 years: 90 hours.
6 to <12 years: 93 hours.
12 to <18 years: 87 hours.
Adults: 104 to 118 hours.
Pediatric: 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.
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