Dosing & Uses
Dosage Forms & Strengths
lyophilized powder for reconstitution
- 250 IU
- 500 IU
- 1000 IU
- 1500 IU
- 2000 IU
- 3000 IU
Hemophilia B, Bleeding Episodes
Indicated for control and prevention of bleeding episodes and perioperative management
Initial dose
- Initial dose = body weight (kg) x desired factor IX increase (% or IU/dL) x reciprocal of observed recovery (IU/dL per IU/kg)
Incremental recovery in previously treated patients (Rixubis)
- For incremental recovery of 0.9 IU/dL, the dose is calculated as follows:
- Dose (IU) = body weight (kg) x desired factor IX increase (% or IU/dL) x 1.1 dL/kg
Incremental recovery in previously treated patients (BeneFIX)
- For incremental recovery of 0.8 IU/dL, the dose is calculated as follows:
- Dose (IU) = body weight (kg) x desired factor IX increase (% or IU/dL) x 1.3 dL/kg
Incremental recovery in previously treated patients (Ixinity)
- For incremental recovery of 0.98 IU/dL, the dose is calculated as follows:
- Dose (IU) = body weight (kg) x desired factor IX increase (% or IU/dL) x 1.02 dL/kg
Control and prevention of bleeding episodes (Rixubis, BeneFIX)
- Minor: Circulating factor IX level required = 20-30 IU/dL; dosing interval 12-24 hr; treatment duration at least 1 day until healing achieved
- Moderate: Circulating factor IX level required = 25-50 IU/dL; dosing interval 12-24 hr; treatment duration 2-7 days until bleeding stops and healing achieved
- Major: Circulating factor IX level required = 50-100 IU/dL; dosing interval 12-24 hr; treatment duration 7-10 days until bleeding stops and healing achieved
Control and prevention of bleeding episodes (Alprolix)
- Minor and moderate: Circulating factor IX level required = 30-60 IU/dL; dosing interval 24 hr prn
- Major: Circulating factor IX level required = 80-100 IU/dL; consider repeating dose after 6-10 hr, then q24hr x3 days, then q48hr until healing achieved
Control and prevention of bleeding episodes (Ixinity)
- Minor: Circulating factor IX level required = 30-60 IU/dL; dosing interval 24 hr prn; 1-3 days until healing achieved
- Moderate: Circulating factor IX level required = 40-80 IU/dL; dosing interval 24 hr prn; 2-7 days until healing achieved
- Major: Circulating factor IX level required = 60-100 IU/dL; dosing interval 12-24 hr prn; 2-14 days until healing achieved
Control and prevention of bleeding episodes (Rebinyn; nonacog beta pegol)
- Minor and moderate: 40 IU/kg IV as a single dose is typically sufficient; additional doses can be give if needed
- Major: 80 IU/kg IV; additional doses of 40 IU/kg can be given
Perioperative management (Rixubis)
- Minor (eg, tooth extraction): Circulating factor IX level required = 30-60 IU/dL; dosing interval 24 hr; treatment duration at least 1 day until healing achieved
- Major: Circulating factor IX level required = 80-100 IU/dL; dosing interval 8-24 hr; treatment duration 7-10 days until bleeding stops and healing achieved
Perioperative management (BeneFIX)
- Minor: Circulating factor IX level required = 20-30 IU/dL; dosing interval 12-24 hr; treatment duration at least 1 day until healing achieved
- Moderate: Circulating factor IX level required = 25-50 IU/dL; dosing interval 12-24 hr; treatment duration 2-7 days until bleeding stops and healing achieved
- Major: Circulating factor IX level required = 50-100 IU/dL; dosing interval 12-24 hr; treatment duration 7-10 days until bleeding stops and healing achieved
Perioperative management (Alprolix)
- Minor and moderate: Circulating factor IX level required = 50-80 IU/dL; a single infusion may be sufficient, may repeat as needed after 24-48 hr until bleeding stopped and healing achieved
- Major: Circulating factor IX level required = 60-100 IU/dL (initial level); consider repeating dose after 6-10 hr, then q24hr x3 days, may then reduce dose and extend dosing interval to q48hr (or longer) until bleeding stopped and healing achieved
Perioperative management (Ixinity)
- Minor, pre-op: Circulating factor IX level required = 50-80 IU/dL
- Minor, post-op: Circulating factor IX level required = 30-80 IU/dL; dosing interval 24 hr; treatment duration 1-5 days depending on type of procedure
- Major, pre-op: Circulating factor IX level required = 60-80 IU/dL
Major, post-op
- Dosing interval 8-24 hr
- Days 1-3: Circulating factor IX level required = 40-60 IU/dL
- Days 4-6: Circulating factor IX level required = 30-50 IU/dL
- Days 7-14: Circulating factor IX level required = 20-40 IU/dL
Perioperative management (Rebinyn)
- Minor: 40 IU/kg IV as a single preoperative dose is typically sufficient; additional doses can be give if needed
- Major: 80 IU/kg IV as a single preoperative dose
Hemophilia B, Routine Prophylaxis
Indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes
Rixubis
- 40-60 IU/kg IV bolus 2x/week; not to exceed infusion rate of 10 mL/min
- Dose titration may be needed depending on patient’s age, bleeding pattern, and physical activity
Alprolix
- Long-acting recombinant Factor IX Fc fusion protein allows for less frequent dosing
- Initial: 50 IU/kg IV once weekly OR 100 IU/kg q10days
- Adjust dose based on individual response
Dosing Considerations
Rixubis: 1 IU/kg is expected to increase circulating level of Factor IX by 0.9 IU/dL of plasma
BeneFIX (adults): 1 IU/kg is expected to increase circulating level of Factor IX by 0.8 IU/dL (range 0.4-1.2 IU/dL)
Alprolix: 1 IU/kg is expected to increase circulating level of Factor IX by 1% (IU/dL)
Rebinyn: Conjugated to a 40-kDa polyethylene glycol molecule, which slows down its removal from the blood circulation; each vial is labeled with the actual Factor IX potency in IU
Dosage Forms & Strengths
lyophilized powder for reconstitution
- 250 IU
- 500 IU
- 1000 IU
- 1500 IU
- 2000 IU
- 3000 IU
Hemophilia B, Bleeding Control
BeneFIX: Approved for children <15 yr; indicated for control and prevention of bleeding episodes and perioperative management
Ixinity: Approved for children ≥12 yr; indicated for control and prevention of bleeding episodes and perioperative management
Alprolix, Rixubix: Approved for children; indicated for control and prevention of bleeding episodes, perioperative management, and routine prophylaxis to prevent/reduce frequency of bleeding episodes
Initial dose
- Initial dose = body weight (kg) x desired factor IX increase (% or IU/dL) x reciprocal of observed recovery (IU/dL per IU/kg)
Incremental recovery in previously treated patients (BeneFIX)
- For incremental recovery of 0.7 IU/dL, the dose is calculated as follows:
- Dose (IU) = body weight (kg) x desired factor IX increase (% or IU/dL) x1.4 dL/kg
Incremental recovery in previously treated patients (Ixinity)
- For incremental recovery of 0.98 IU/dL, the dose is calculated as follows:
- Dose (IU) = body weight (kg) x desired factor IX increase (% or IU/dL) x 1.02 dL/kg
Control and prevention of bleeding episodes (BeneFIX)
- Minor: Circulating factor IX level required = 20-30 IU/dL; dosing interval 12-24 hr; treatment duration at least 1 day until healing achieved
- Moderate: Circulating factor IX level required = 25-50 IU/dL; dosing interval 12-24 hr; treatment duration 2-7 days until bleeding stops and healing achieved
- Major: Circulating factor IX level required = 50-100 IU/dL; dosing interval 12-24 hr; treatment duration 7-10 days until bleeding stops and healing achieved
Control and prevention of bleeding episodes (Alprolix)
- Minor and moderate: Circulating factor IX level required = 30-60 IU/dL; dosing interval 24 hr prn
- Major: Circulating factor IX level required = 80-100 IU/dL; consider repeating dose after 6-10 hr, then q24hr x3 days, then q48hr until healing achieved
Control and prevention of bleeding episodes (Ribuxis)
- Minor: Circulating factor IX level required = 20-30 IU/dL; dosing interval 12-24 hr prn; at least 1 day until healing achieved
- Moderate: Circulating factor IX level required = 25-50 IU/dL; dosing interval 12-24 hr prn; at least 2-7 days until healing achieved
- Major: Circulating factor IX level required = 50-100 IU/dL; dosing interval 12-24 hr prn; at least 7-10 days until healing achieved
Control and prevention of bleeding episodes (Ixinity)
- Minor: Circulating factor IX level required = 30-60 IU/dL; dosing interval 24 hr prn; 1-3 days until healing achieved
- Moderate: Circulating factor IX level required = 40-80 IU/dL; dosing interval 24 hr prn; 2-7 days until healing achieved
- Major: Circulating factor IX level required = 60-100 IU/dL; dosing interval 12-24 hr prn; 2-14 days until healing achieved
Control and prevention of bleeding episodes (Rebinyn; nonacog beta pegol)
- Minor and moderate: 40 IU/kg IV as a single dose is typically sufficient; additional doses can be give if needed
- Major: 80 IU/kg IV; additional doses of 40 IU/kg can be given
Perioperative management (BeneFIX)
- Minor: Circulating factor IX level required = 20-30 IU/dL; dosing interval 12-24 hr; treatment duration at least 1 day until healing achieved
- Moderate: Circulating factor IX level required = 25-50 IU/dL; dosing interval 12-24 hr; treatment duration 2-7 days until bleeding stops and healing achieved
- Major: Circulating factor IX level required = 50-100 IU/dL; dosing interval 12-24 hr; treatment duration 7-10 days until bleeding stops and healing achieved
Perioperative management (Alprolix)
- Minor and moderate: Circulating factor IX level required = 50-80 IU/dL; a single infusion may be sufficient, may repeat as needed after 24-48 hr until bleeding stopped and healing achieved
- Major: Circulating factor IX level required = 60-100 IU/dL (initial level); consider repeating dose after 6-10 hr, then q24hr x3 days, may then reduce dose and extend dosing interval to q48hr (or longer) until bleeding stopped and healing achieved
Perioperative management (Rixubis)
- Minor: Circulating factor IX level required = 30-60 IU/dL; dosing interval 24 hr; at least 1 day until healing achieved
- Major: Circulating factor IX level required = 80-100 IU/dL; dosing interval 8-24 hr; at least 7-10 days until healing achieved
Perioperative management (Ixinity)
- Minor, pre-op: Circulating factor IX level required = 50-80 IU/dL
- Minor, post-op: Circulating factor IX level required = 30-80 IU/dL; dosing interval 24 hr; treatment duration 1-5 days depending on type of procedure
- Major, pre-op: Circulating factor IX level required = 60-80 IU/dL
Major, post-op
- Dosing interval 8-24 hr
- Days 1-3: Circulating factor IX level required = 40-60 IU/dL
- Days 4-6: Circulating factor IX level required = 30-50 IU/dL
- Days 7-14: Circulating factor IX level required = 20-40 IU/dL
Perioperative management (Rebinyn)
- Minor: 40 IU/kg IV as a single preoperative dose is typically sufficient; additional doses can be give if needed
- Major: 80 IU/kg IV as a single preoperative dose
Hemophilia B, Routine Prophylaxis
Indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes
Alprolix
- Long-acting recombinant Factor IX Fc fusion protein allows for less frequent dosing
- Initial: 50 IU/kg IV once weekly OR 100 IU/kg q10days
- Adjust dose based on individual response
Rixubis
- <12 years: 60-80 IU/kg IV 2x/week
- ≥12 years: 40-60 IU/kg IV 2x/week
- Maximum infusion rate is 10 mL/min
- Adjust the dose based on the individual patient’s age, bleeding pattern, and physical activity
Dosing Considerations
BeneFIX (children <15 years): 1 IU/kg is expected to increase circulating level of Factor IX by 0.7 IU/dL (range 0.2-2.1 IU/dL)
Alprolix: 1 IU/kg is expected to increase circulating level of Factor IX by 1% (IU/dL)
Alprolix (<12 years): May have higher Factor IX bodyweight-adjusted clearance, shorter half-life, and lower recovery; therefore, higher dose/kg or more frequent dosing may be needed
Rixubis (<12 years): 1 IU/kg is expected to increase circulating level of Factor IX by 0.7 IU/dL
Rixubis (≥12 years): 1 IU/kg is expected to increase circulating level of Factor IX by 0.9 IU/dL
Rebinyn: Conjugated to a 40-kDa polyethylene glycol molecule, which slows down its removal from the blood circulation; each vial is labeled with the actual Factor IX potency in IU
Adverse Effects
>10% (BeneFIX)
Headache (10.8%)
1-10% (BeneFIX)
Dizziness (7.7%)
Injection site reaction (7.7%)
Injection site pain (6.2%)
Nausea (6.2%)
Rash (6.2%)
Taste perversion (4.6%)
Hives (3.1%)
Flushing (3.1%)
Fever (3.1%)
Factor IX inhibition (1.5%)
Blurred vision (1.5%)
Vomiting (1.5%)
Cellulitis at IV site (1.5%)
Phlebitis at IV site (1.5%)
Shaking (1.5%)
Drowsiness (1.5%)
Renal infarct (1.5%)
Dry cough (1.5%)
Hypoxia (1.5%)
Chest tightness (1.5%)
1-10% (Rixubis)
Factor IX or furin antibodies (7.7%)
Dysgeusia (1.1%)
Pain in extremity (1.1%)
Positive furin antibody test (1.1%)
1-10% (Alprolix)
Headache (1.7%)
Oral paresthesia (1.7%)
<1% (Alprolix)
Dizziness
Dysgeusia
Breath odor
Fatigue
Infusion site pain
Palpitations
Obstructive uropathy
Hypotension
Warnings
Contraindications
Hypersensitivity to product or its excipients including hamster protein
Disseminated intravascular coagulation (DIC)
Signs of fibrinolysis
Cautions
Hypersensitivity reactions including anaphylaxis reported, particularly with initial exposure in previously untreated patients Factor IX inhibitors may develop
Nephrotic syndrome reported
Thromboembolic complications may occur (eg, PE, venous or arterial thrombosis); monitor for thrombotic and consumptive coagulopathy, especially in patients with liver disease, signs of fibrinolysis, peri- and post-operatively, or at risk for thrombotic events or DIC
Monitor Factor IX activity plasma levels by the one-stage clotting assay to confirm factor IX levels achieved and maintained
Pregnancy & Lactation
Pregnancy Category: C
Lactation: Unknown if distributed in human breast milk
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Temporarily replaces missing clotting factor IX which corrects and/or prevents bleeding
Absorption
Rixubis
- Peak plasma concentration: 66.2-72.7 IU/dL
- AUC: 1207-1305 IU•hr/dL
BeneFIX
- Peak plasma concentration: 54.5 IU/dL
- AUC: 548-940 IU•hr/dL
Alprolix
- Peak plasma concentration: 46 IU/dL
- 1619 IU•hr/dL
Rebinyn
- Peak plasma concentration: 65.5-97.9 IU/d
- AUC: 9072-9280 IU·hr/dL
Distribution
Rixubis
- Vd: 201.9-178.6 mL/kg
Alprolix
- Vd: 327 mL/kg
Rebinyn
- Vd: 60.5-64.8 mL/kg
Elimination
Rixubis
- Half-life: 25.4-26.7 hr
- Clearance: 6-6.4 mL/kg/hr
BeneFIX
- Half-life: 18.1-22.4 hr (adults); 19.8 hr (children 2-12 years); 21.1 hr (children 12-15 years)
- Clearance: ~8.5 mL/kg/hr
Alprolix
- Half-life: 86.52 hr
- Clearance: 3.3 mL/kg/hr
Rebinyn
- Half-life: 103.1-114.9 hr
- Clearance: 0.4 mL/hr/kg
Administration
IV Preparation
BeneFIX, Alprolix, Rebinyn: Use the adapter and supplied diluent syringe to reconstitute each vial (see package instructions)
Rixubis: Use the Baxject II device and sterile water for injection provided in each kit to reconstitute each vial (see package instructions)
IV Administration
Safety and efficacy of administration by continuous infusion has not been established
BeneFIX: Administer IV over several minutes
Rixubis, Alprolix: Administer by IV bolus at rate not to exceed 10 mL/min
Rebinyn: Administer IV over 1-4 minutes
Storage
Unopened vials
- Refrigerated: Store between 2-8°C (35-46°F) in original carton for up to 18 months; do not freeze
- Room temperature: May store at room temperature, not to exceed 30°C (86°F) for up to 6 months within the 18 month time period (mark carton on date removed from refrigerator)
- After storage at room temperature, do not return the product to the refrigerator
Reconstituted vials
- Use within 3 hr following reconstitution
- Do not refrigerate after reconstitution
- Discard partially used vials
Images
Patient Handout
Formulary
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