Factor IX, recombinant human: Drug information

(For additional information see "Factor IX, recombinant human: Patient drug information" and see "Factor IX, recombinant human: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

Brand Names: US

BeneFIX;
Ixinity;
Rixubis

Brand Names: Canada

BeneFIX;
Rixubis

Pharmacologic Category

Antihemophilic Agent

Dosing: Adult

Hemophilia B, without inhibitors

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):

BeneFIX IVR: 0.76.

Ixinity IVR: 0.98.

Rixubis IVR: 0.9.

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.

**Factor IX (Recombinant) WFH Treatment Recommendations^a**
Type of hemorrhage or surgery	Lower dose practice pattern		Higher dose practice pattern
Type of hemorrhage or surgery	Desired peak factor IX level (units/dL)	Treatment duration (days)	Desired peak factor IX level (units/dL)	Treatment duration (days)
^aWFH = World Federation of Hemophilia (WFH [Srivastava 2020]). ^bMay be longer if response is inadequate. ^c A single dose may be sufficient for some joint bleeds; determine need for additional doses based on clinical response. ^dSometimes longer as secondary prophylaxis during physical therapy.
Joint	10 to 20	1 to 2^b,c	40 to 60	1 to 2^b,c
Superficial muscle/no neurovascular compromise (except iliopsoas)	10 to 20	2 to 3^b	40 to 60	2 to 3^b
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 5^d	30 to 60	3 to 5^d
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
Maintenance	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 (BeneFIX) for 50 kg patient with desired peak factor IX level of 35 units/dL, baseline factor IX level of 5 units/dL, IVR = 0.76:

Factor IX units required = [(35 units/dL − 5 units/dL) × 50 kg)] ⁄ 0.76 = 1,974 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.

**Factor IX (Recombinant) Administration Frequency According to Clinical Scenario**
Product	Bleeding event			Surgery
Product	Minor severity	Moderate severity	Major severity	Minor bleeding risk	Major bleeding risk
BeneFIX	Every 12 to 24 hours	Every 12 to 24 hours	Every 12 to 24 hours	Every 12 to 24 hours	Every 12 to 24 hours
Ixinity	Every 24 hours	Every 24 hours	Every 12 to 24 hours	Every 24 hours	Every 8 to 24 hours
Rixubis	Every 12 to 24 hours	Every 12 to 24 hours	Every 12 to 24 hours	Every 24 hours	Every 8 to 24 hours

Continuous infusion administration (Batorova 2002; Batorova 2012; Chowdary 2001; Holme 2018; Poon 2012; Ragni 2002; Rickard 1995; WFH [Srivastava 2020]):

Note: Continuous infusion administration is preferred over intermittent bolus administration for patients requiring prolonged treatment courses (eg, postoperative management after surgery with major bleeding risk). To ensure safe and effective use, only products with extended stability information should be used. Extended stability information may not be available for all products; contact product manufacturer to obtain current recommendations. Use of a smart infusion pump with small volume infusion capability is also necessary.

IV: Administer an initial bolus to achieve the desired factor IX level (see steps 1 to 3 under "Intermittent bolus dosing"), then initiate continuous infusion of 4 to 6 units/kg/hour. Adjust dose based on frequent factor assays (at least daily) and calculation of factor IX clearance at steady state using the following equations.

Factor IX clearance (mL/kg/hour) = (current infusion rate in units/kg/hour) divided by (measured factor IX level in units/mL)

New infusion rate (units/kg/hour) = (factor IX clearance in mL/kg/hour) × (desired factor IX level in units/mL)

Note: With infusion dose increases, re-bolus should be considered to achieve target factor IX level more quickly. See steps 1 to 3 under "Intermittent IV bolus dosing" to determine re-bolus dose.

Routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with moderate/severe hemophilia B without inhibitors:

Note: Dosing should be tailored to ensure trough factor IX levels of at least 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]).

BeneFIX: IV: 100 units/kg once weekly; may titrate dose or frequency based on patient’s clinical response.

Ixinity: IV: 40 to 70 units/kg twice weekly; may titrate dose based on patient’s age, bleeding pattern, and physical activity.

Rixubis: IV: 40 to 60 units/kg twice weekly; may titrate dose depending upon age, bleeding pattern, and physical activity.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; monitor factor IX levels.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; monitor factor IX levels. Use with caution due to the risk of thromboembolic complications.

Dosing: Obesity: Adult

There are insufficient data to recommend the best dosing weight to use in patients with obesity. Dose adjustments should ultimately be made based on individual patient response to therapy. Due to the paucity of data, refer to institutional protocols. Refer to adult dosing for indication-specific dosing.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Factor IX, recombinant human: Pediatric drug information")

Hemophilia B

Hemophilia B (Christmas disease): Individualize dosage based on clinical response and factor IX activity evaluated at baseline and at regular intervals during treatment.

General dosing for control or prevention of bleeding episodes or perioperative management: IV: Note: Dosage is expressed in units of factor IX activity and must be individualized based on formulation, severity of factor IX deficiency, extent and location of bleed, individualized incremental recovery using factor IX activity assays, and clinical situation of patient.

Infants, Children, and Adolescents (ages vary by product; see product-specific labeling for approved ages): 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 observed recovery (as units/kg per units/dL)

Reciprocal of average observed recovery (as units/kg per units/dL):

BeneFIX:

Infants, Children, and Adolescents <15 years: 1.4

Adolescents ≥15 years: 1.3

Ixinity: Children ≥12 years and Adolescents: 1.02

Rixubis:

Infants and Children <12 years: 1.4

Children ≥12 years and Adolescents: 1.1

For example for BeneFIX, for a 100% level in a 25 kg patient <15 years who has an actual level of 20%: Number of factor IX Units needed = 25 kg x 80% x 1.4 units/kg per units/dL = 2,800 units

Treatment recommendations (WFH [Srivastava 2020]): Note: Ages vary by product; see product-specific labeling for approved ages. Factor IX level may either be expressed as % or as units/dL.

Intermittent IV: The following recommendations reflect WFH guideline recommendations for higher dose practice patterns; this dosing is typically used in areas where no significant resource constraints exist; recommendations may vary from those found within prescribing information or practitioner preference. Frequency is based on type of bleed or surgery and varies by product; see specific product labeling for details. If factor IX levels are available, subsequent doses should be based on the half-life of factor IX and on the recovery in an individual patient for a particular product.

Site of Hemorrhage/Clinical Situation	Desired Factor IX Peak Level	Frequency^A	Duration
^AFrequency is based on type of bleed or surgery and varies by product; see specific product labeling for details.
Joint	40% to 60%	Every 12 to 24 hours	1 to 2 days, may be longer if response is inadequate
Superficial muscle/no neurovascular compromise	40% to 60%	Every 12 to 24 hours	2 to 3 days, sometimes longer if response is inadequate
Iliopsoas and deep muscle with neurovascular injury, or substantial blood loss	Initial: 60% to 80%	Every 12 to 24 hours	Initial: 1 to 2 days
	Maintenance: 30% to 60%	Every 12 to 24 hours	Maintenance: 3 to 5 days, sometimes longer as secondary prophylaxis during physiotherapy
CNS/Head	Initial: 60% to 80%	Every 12 to 24 hours	Initial: 1 to 7 days
CNS/Head	Maintenance: 30%	Every 12 to 24 hours	Maintenance: 8 to 21 days
Throat and neck	Initial: 60% to 80%	Every 12 to 24 hours	Initial: 1 to 7 days
Throat and neck	Maintenance: 30%	Every 12 to 24 hours	Maintenance: 8 to 14 days
Gastrointestinal	Initial: 60% to 80%	Every 12 to 24 hours	Initial: 7 to 14 days
Gastrointestinal	Maintenance: 30%	Every 12 to 24 hours	Maintenance: Not specified
Renal	40%	Every 12 to 24 hours	3 to 5 days
Deep laceration	40%	Every 12 to 24 hours	5 to 7 days
Surgery (major)	Preop: 60% to 80%	Single dose
	Postop: 40% to 60%	Every 8 to 24 hours	Postop: 1 to 3 days
	Postop: 30% to 50%		Postop: 4 to 6 days
	Postop: 20% to 40%		Postop: 7 to 14 days
Surgery (minor)	Preop: 50% to 80%	Single dose
Surgery (minor)	Postop: 30% to 80%	Every 12 to 24 hours	Postop: 1 to 5 days depending on procedure type

Continuous IV infusion: Limited data available: Infants, Children, and Adolescents: Note: In general, administration of factor IX 7.5 units/kg/hour will increase circulating factor IX levels by 1 unit/mL (Prelog 2016).

Control and prevention of bleeding episodes and perioperative management: Note: For patients who require prolonged periods of treatment (eg, intracranial hemorrhage or surgery) to avoid peaks and troughs associated with intermittent infusions (Batorova 2002; Morfini 2008; Poon 2012; Prelog 2016; WFH [Srivastava 2020]). Evidence supporting the use of continuous infusion is primarily with BeneFIX (Chowdary 2001); however, manufacturer's labeling states that safety and efficacy of BeneFIX administration by continuous infusion has not been established.

Following initial bolus to achieve the desired factor IX level (Poon 2012): Initial dosing: 4 to 6 units/kg/hour; adjust dose based on frequent factor IX assays and calculation of factor IX clearance at steady-state using the following equations:

Factor IX clearance (mL/kg/hour) = (current infusion rate in units/kg/hour) / (plasma Factor IX level in units/mL)

New infusion rate (units/kg/hour) = (factor IX clearance in mL/kg/hour) x (desired plasma level in units/mL)

Routine prophylaxis: Note: Adjust dose based on clinical response.

Product-specific dosing:

BeneFIX:

Infants, Children, and Adolescents: IV: 100 units/kg/dose once weekly; titrate dose or frequency based on patient's clinical response. Note: For pediatric patients <12 years of age, more frequent or higher doses may be required due to lower recovery, shorter half-life, and higher drug clearance.

Ixinity: Children ≥12 years and Adolescents: IV: 40 to 70 units/kg/dose twice weekly; titrate dose depending upon age, bleeding pattern, and physical activity.

Rixubis:

Infants and Children <12 years: IV: 60 to 80 international units/kg/dose 2 times weekly.

Children ≥12 years and Adolescents: IV: 40 to 60 international units/kg/dose 2 times weekly.

Guideline dosing (WFH [Srivastava 2020]): Note: Maintain factor IX trough levels >3% to 5% or higher as clinically indicated. Dose should be individualized; dose intensity should take into account disease severity, patient's activity and lifestyle, and pharmacokinetic properties of product and should be adjusted if breakthrough bleeding occurs. See guidelines for in-depth discussion of risks and benefits of each dosing approach.

Infants, Children, and Adolescents: IV:

High dose: 40 to 60 units/kg/dose 2 times weekly.

Intermediate dose: 20 to 40 units/kg/dose 2 times weekly.

Low dose: 10 to 15 units/kg/dose 2 times weekly. Note: Low dose prophylaxis may be used in young patients as initial therapy; close monitoring is required since patients are at a higher risk for bleeding until escalation occurs.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; monitor factor IX levels.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; monitor factor IX levels. Use with caution due to the risk of thromboembolic complications.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%

Immunologic: Antibody development (2% to 30%; against factor IX, CHO proteins, and furin [indeterminate specificity]; may be neutralizing)

Nervous system: Headache (3% to 11%)

1% to 10%

Cardiovascular: Chest tightness (2%), flushing (3%)

Dermatologic: Pruritic rash (1%), skin rash (2% to 6%), urticaria (3% to 5%)

Gastrointestinal: Dysgeusia (1% to 5%), nausea (6%), vomiting (2%)

Hematologic & oncologic: Factor IX inhibitor in hemophilia B (2% to 3%)

Infection: Influenza (1%)

Local: Cellulitis at injection site (2%), discomfort at injection site (1%), injection site phlebitis (2%), injection site reaction (2% to 8%), pain at injection site (6%)

Nervous system: Apathy (1%), chills (2%), depression (1%), dizziness (8%), drowsiness (2%), lethargy (1%)

Neuromuscular & skeletal: Asthenia (1%), limb pain (1%), tremor (2%)

Ophthalmic: Blurred vision (2%)

Renal: Renal infarction (2%)

Respiratory: Dry cough (2%), dyspnea (3%), hypoxia (2%)

Miscellaneous: Fever (3%)

Postmarketing

Cardiovascular: Deep vein thrombosis, hypotension, peripheral thrombophlebitis, superior vena cava syndrome (neonates), thrombosis

Genitourinary: Nephrotic syndrome (associated with immune tolerance induction)

Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction

Contraindications

Life-threatening, immediate hypersensitivity reactions (including anaphylaxis) to coagulation factor IX, hamster protein, or any component of the formulation; disseminated intravascular coagulation (Rixubis); signs of fibrinolysis (Rixubis).

Warnings/Precautions

Concerns related to adverse effects:

• Antibody formation: The development of factor IX antibodies (or inhibitors) has been reported with factor IX therapy (usually occurs within the first 10 to 20 exposure days); the risk of severe hypersensitivity reactions occurring may be greater in these patients. When clinical response is suboptimal, the patient has reached a specified number of exposure days, or patient is to undergo surgical procedure, screen for inhibitors. Patients with severe hemophilia compared to those with mild or moderate hemophilia are more likely to develop inhibitors (WFH [Srivastava 2020]).

• Hypersensitivity reactions: Hypersensitivity reactions (including anaphylaxis) may occur; risk is highest during the early phases of initial exposure in previously untreated patients, especially those with high-risk gene mutations. Delayed reactions (up to 20 days after infusion) in previously untreated patients may also occur. Due to potential for allergic reactions, the initial ~10 to 20 administrations should be performed under appropriate medical supervision. Hypersensitivity reactions have frequently occurred in close temporal association with the development of factor IX inhibitors; patients experiencing allergic reactions should be evaluated for factor IX inhibitors. If hypersensitivity reactions occur, discontinue immediately; in the case of severe allergic reactions, consider the use of alternative hemostatic measures (WFH [Srivastava 2020]).

• Nephrotic syndrome: Nephrotic syndrome has been reported following attempted immune tolerance induction in hemophilia B patients with factor IX inhibitors and a history of allergic reactions. Safety and efficacy in this situation have not been established.

• Thrombotic events: Thromboembolism (eg, pulmonary embolism, venous/arterial thrombosis) may occur. Monitor for early signs of thromboembolism and coagulopathy in patients with hepatic disease, fibrinolysis, peri- and postoperative patients, or patients at risk for thromboembolic events or disseminated intravascular coagulation (DIC). The benefit of treatment should be weighed against the risk of complications in patients with DIC or those at risk for DIC or thromboembolic events. Reports of thrombotic events have also been reported in patients receiving continuous infusion through a central venous catheter, including life-threatening superior vena cava syndrome in critically ill neonates.

Disease-related concerns:

• Hepatic impairment: Use with extreme caution in patients with hepatic impairment due to the increased risk of thromboembolic complications.

Dosage form specific issues:

• Hamster protein: May contain trace amounts of Chinese hamster proteins; hypersensitivity to these proteins may develop.

• 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.

Other warnings/precautions:

• Clinical response: Response to factor IX administration may vary. If bleeding is not controlled with the recommended dose, determine plasma level of factor IX and follow with a sufficient dose to achieve satisfactory clinical response. If plasma levels of factor IX fail to increase as expected or bleeding continues, suspect the presence of an inhibitor; test as appropriate.

Warnings: Additional Pediatric Considerations

Use with caution when administering to neonates; the safety and efficacy of continuous infusion administration has not been established; thrombotic events have been reported in patients receiving continuous infusion of recombinant Factor IX through a central venous catheter, including life-threatening superior vena cava syndrome in neonates.

Dosage Forms Considerations

Strengths expressed with approximate values. Consult individual vial labels for exact potency within each vial.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Kit, Intravenous [preservative free]:

BeneFIX: 250 units, 500 units, 1000 units, 2000 units, 3000 units [contains polysorbate 80]

Solution Reconstituted, Intravenous [preservative free]:

Ixinity: 250 units (1 ea) [contains mouse (murine) and/or hamster protein, polysorbate 80]

Ixinity: 250 units (1 ea) [contains polysorbate 80]

Ixinity: 500 units (1 ea) [contains mouse (murine) and/or hamster protein, polysorbate 80]

Ixinity: 500 units (1 ea) [contains polysorbate 80]

Ixinity: 1000 units (1 ea) [contains mouse (murine) and/or hamster protein, polysorbate 80]

Ixinity: 1000 units (1 ea) [contains polysorbate 80]

Ixinity: 1500 units (1 ea) [contains mouse (murine) and/or hamster protein, polysorbate 80]

Ixinity: 1500 units (1 ea) [contains polysorbate 80]

Ixinity: 2000 units (1 ea) [contains mouse (murine) and/or hamster protein, polysorbate 80]

Ixinity: 2000 units (1 ea) [contains polysorbate 80]

Ixinity: 3000 units (1 ea) [contains mouse (murine) and/or hamster protein, polysorbate 80]

Ixinity: 3000 units (1 ea) [contains polysorbate 80]

Rixubis: 250 units (1 ea); 500 units (1 ea); 1000 units (1 ea); 2000 units (1 ea); 3000 units (1 ea) [contains polysorbate 80]

Generic Equivalent Available: US

May be product dependent

Pricing: US

Kit (BeneFIX Intravenous)

250 unit (Price provided is per AHF Unit): $2.04

500 unit (Price provided is per AHF Unit): $2.04

1000 unit (Price provided is per AHF Unit): $2.04

2000 unit (Price provided is per AHF Unit): $2.04

3000 unit (Price provided is per AHF Unit): $2.04

Solution (reconstituted) (Ixinity Intravenous)

250 unit (Price provided is per AHF Unit): $2.38

500 unit (Price provided is per AHF Unit): $2.38

1000 unit (Price provided is per AHF Unit): $2.38

1500 unit (Price provided is per AHF Unit): $2.38

2000 unit (Price provided is per AHF Unit): $2.38

3000 unit (Price provided is per AHF Unit): $2.38

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.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Kit, Intravenous:

BeneFIX: 250 units [DSC], 500 units, 1000 units, 2000 units, 3000 units

Solution Reconstituted, Intravenous:

Generic: 250 units (1 ea); 500 units (1 ea); 1000 units (1 ea); 2000 units (1 ea); 3000 units (1 ea)

Administration: Adult

IV: Solution should be infused at room temperature. Safety and efficacy of continuous infusion administration have not been determined.

IV administration only:

Rixubis: For bolus infusion only; maximum rate of administration is 10 mL/minute

BeneFIX: Should be infused slowly over several minutes. Rate of administration should be determined by the response and comfort of the patient. Do not administer as a continuous infusion.

Ixinity: Rate of administration should be determined by the comfort of the patient; maximum rate of administration is 10 mL/minute

Continuous infusion (off-label rate): Some products may be administered as a continuous infusion to avoid peaks and troughs associated with intermittent infusions in patients who require prolonged treatment periods. Use a smart infusion pump with small volume infusion capability. Refer to protocols for product selection and preparation details (Batorova 2002; Batorova 2012; Chowdary 2001; Holme 2018; Poon 2012; Ragni 2002; Rickard 1995; WFH [Srivastava 2020]).

Administration: Pediatric

Parenteral: IV administration only; use administration sets/tubing provided by manufacturer (if provided). Solution should be infused at room temperature. With patients who have had allergic reactions during factor IX infusion, administration of antihistamine prior to infusion may be necessary (WFH [Srivastava 2020]).

Intermittent IV:

BeneFIX: Should be infused slowly over several minutes. Rate of administration should be determined by the response and comfort of the patient.

Ixinity: Rate of administration should be determined by the comfort of the patient; maximum rate of administration is 10 mL/minute.

Rixubis: Maximum rate of administration is 10 mL/minute.

Continuous IV infusion: Limited data available in select patients: Infuse as directed. Evidence supporting the use of continuous infusion is primarily with BeneFIX (Chowdary 2001); however, manufacturer's labeling states that safety and efficacy of BeneFIX and Rixubis administration by continuous infusion has not been established. Further dilution after initial reconstitution is unnecessary (Batorova 2002; Prelog 2016).

Use: Labeled Indications

Hemophilia B: On-demand treatment and control of bleeding episodes in patients with factor IX deficiency (hemophilia B [Christmas disease]); perioperative management in patients with hemophilia B; routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia B.

Limitations of use: Not indicated for induction of immune tolerance in patients with hemophilia B.

Medication Safety Issues

Sound-alike/look-alike issues:

Factor IX may be confused with Factor IX Complex

Metabolism/Transport Effects

None known.

Drug Interactions

There are no known significant interactions.

Pregnancy Considerations

Pregnant carriers of hemophilia B may have an increased bleeding risk following 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]).

Breastfeeding Considerations

It is not known if factor IX (recombinant) is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.

Monitoring Parameters

Monitoring assay selection: For recombinant nonmodified FIX products (BeneFIX, Ixinity, Rixubis), the World Federation of Hemophilia (WFH) recommends use of a one-stage FIX activity assay calibrated with a plasma standard traceable to a WHO international standard. Note: Chromogenic FIX assays have been reported to underestimate FIX activity of recombinant FIX concentrates and should not be used (WFH [Srivastava 2020]).

Monitoring frequency: During treatment of an acute bleeding event or in the perioperative setting using intermittent bolus administration, factor IX levels should be measured at baseline, and as peaks 15 to 30 minutes after infusion to assess target level achievement. The frequency of peak factor IX activity monitoring during active treatment depends on the indication, clinical response, and treatment day. Measurement of FIX trough levels may aid in calculation of subsequent doses (WFH [Srivastava 2020]).

When administered as a continuous infusion, monitor factor IX activity at baseline, peak factor IX activity 15 to 30 minutes after initial bolus administration, and at least daily while on continuous infusion therapy. Frequently assess proper functioning of vascular access devices and infusion pumps for pump failure (WFH [Srivastava 2020]).

For long-term bleeding prophylaxis, trough factor IX measurements should be obtained to tailor prophylaxis regimens, with the goal of achieving factor IX troughs >3 to 5 units/dL; prophylaxis targets should be tailored to individual level of activity, lifestyle, and pharmacokinetics.

Additional monitoring considerations: Heart rate and blood pressure before and during IV administration, signs of hypersensitivity reactions (which may be an early sign of inhibitor development), hemoglobin/hematocrit, and signs and symptoms of intravascular hemolysis.

For both intermittent bolus and continuous infusion administration, lower than expected factor IX recovery or reduced half-life are early signs of inhibitor formation.

Reference Range

Classification of hemophilia; normal is defined as 100% factor IX (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.

Mechanism of Action

Replaces deficient clotting factor IX. Hemophilia B, or Christmas disease, is an X-linked inherited disorder of blood coagulation characterized by insufficient or abnormal synthesis of the clotting protein factor IX. Factor IX is a vitamin K-dependent coagulation factor which is synthesized in the liver. Factor IX is activated by factor XIa in the intrinsic coagulation pathway. Activated factor IX (IXa) in combination with factor VII:C activates factor X to Xa, resulting ultimately in the conversion of prothrombin to thrombin and the formation of a fibrin clot. The infusion of exogenous factor IX to replace the deficiency present in hemophilia B temporarily restores hemostasis.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: V_ss:

BeneFIX: Children <2 years of age: 252 ± 35 mL/kg; Children 2 to <6 years of age: 257 ± 25 mL/kg; Children 6 to <12 years of age: 303 mL/kg; Children ≥12 years of age, Adolescents, and Adults: 229 ± 57 mL/kg.

Ixinity: 102 to 314 mL/kg.

Rixubis: Children <6 years of age: ~0.3 L/kg; Children ≥6 years of age, Adolescents, and Adults: ~0.2 L/kg.

Half-life elimination:

BeneFIX:

Children <2 years of age: Mean: 15.6 ± 1.2 hours.

Children 2 to <6 years of age: Mean: 16.7 ± 1.9 hours.

Children 6 to <12 years of age: Mean: 16.3 hours.

Children ≥12 years of age, Adolescents, and Adults: 23.1 ± 4.4 hours.

Ixinity: Children ≥12 years of age, Adolescents, and Adults: Mean: 24 ± 7 hours; range: 13 to 43 hours.

Rixubis:

Children <6 years of age: Mean: 27.7 ± 2.7 hours; range: 24 to 32.2 hours.

Children 6 to <12 years of age: 25.3 ± 1.8 hours; range: 23.7 to 30.3 hours.

Children ≥12 years of age, Adolescents, and Adults:

Single dose: Mean: 26.7 ± 9.6 hours; range: 15.8 to 52.3 hours.

Repeat dosing: Mean: 25.4 ± 6.9 hours; range: 16.2 to 42.2 hours.

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Benefix;
(AR) Argentina: Benefix;
(AT) Austria: Benefix;
(AU) Australia: Benefix;
(BE) Belgium: Benefix;
(BR) Brazil: Benefix;
(CH) Switzerland: Benefix;
(CO) Colombia: Benefix;
(CZ) Czech Republic: Benefix;
(EG) Egypt: Benefix;
(ES) Spain: Benefix;
(FI) Finland: Benefix;
(GB) United Kingdom: Benefix;
(GR) Greece: Benefix;
(HU) Hungary: Benefix;
(ID) Indonesia: Benefix;
(IN) India: Benefix;
(IT) Italy: Benefix;
(JO) Jordan: Benefix;
(JP) Japan: Benefix;
(KR) Korea, Republic of: Benefix;
(KW) Kuwait: Benefix;
(LB) Lebanon: Benefix;
(LU) Luxembourg: Benefix;
(MX) Mexico: Benefix;
(MY) Malaysia: Benefix;
(NL) Netherlands: Benefix;
(NO) Norway: Benefix;
(NZ) New Zealand: Benefix;
(PL) Poland: Benefix;
(PR) Puerto Rico: Benefix;
(PT) Portugal: Benefix;
(PY) Paraguay: Factor de coagulacion ix octapharma;
(QA) Qatar: Benefix;
(RO) Romania: Benefix;
(RU) Russian Federation: Agemfil b | Innonafactor;
(SA) Saudi Arabia: Benefix;
(SE) Sweden: Benefix;
(SG) Singapore: Benefix;
(SI) Slovenia: Benefix;
(SK) Slovakia: Benefix;
(TN) Tunisia: Benefix;
(TR) Turkey: Benefix;
(TW) Taiwan: Benefix;
(UA) Ukraine: Benefix;
(UY) Uruguay: Benefix

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Topic 88573 Version 218.0

خرید پکیج

Factor IX, recombinant human: Drug information