Factor IX, human plasma-derived: Drug information

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

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

Brand Names: US

AlphaNine SD;
Mononine [DSC]

Brand Names: Canada

Immunine VH

Pharmacologic Category

Antihemophilic Agent;
Blood Product Derivative

Dosing: Adult

Hemophilia B, without inhibitors

Hemophilia B, without inhibitors:

Note: Contains nondetectable levels of factors II, VII, and X. Therefore, NOT INDICATED for replacement therapy of other clotting factors besides factor IX or for reversal of anticoagulation due to vitamin K antagonists or other anticoagulants, for hemophilia A patients with factor VIII inhibitors, or for 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):

Alphanine SD IVR: 1 (manufacturer's labeling).

Mononine IVR: 1.2 (White 1995).

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 (Human) 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 Hemophilia Federation; (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):
Preop	50 to 70	-	60 to 80	-
Postop	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):
Preop	40 to 80		50 to 80
Postop	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 (Mononine) for 50 kg patient with desired peak factor IX level of 35 units/dL, baseline factor IX level of 5 units/dL, IVR = 1.2:

Factor IX units required = [(35 units/dL − 5 units/dL) × 50 kg] / 1.2 = 1,250 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 (human) Administration Frequency According to Clinical Scenario**
Product	Bleeding event			Surgery
Product	Minor severity	Moderate severity	Major severity	Minor bleeding risk	Major bleeding risk
Alphanine SD	Every 12 hours	Every 12 hours	Every 12 hours	Every 12 hours	Every 12 hours
Mononine	Every 24 hours	No recommendation	Every 18 to 30 hours depending on patient half-life	Every 24 hours	Every 18 to 30 hours depending on patient half-life

Continuous infusion dosing (Batorova 2002; Holme 2018; Hoots 2003; Ménart 1998; Poon 2012; Rickard 1995; Schulman 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 below 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:

IV: 40 to 60 factor IX units/kg twice weekly. 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]).

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, human plasma-derived: Pediatric drug information")

NOTE: Contains nondetectable levels of factors II, VII, and X; therefore, NOT INDICATED for replacement therapy of any other clotting factor besides factor IX or for reversal of anticoagulation due to either vitamin K antagonists or other anticoagulants (eg, dabigatran), for hemophilia A patients with factor VIII inhibitors, or for patients in a hemorrhagic state caused by reduced production of liver-dependent coagulation factors (eg, hepatitis, cirrhosis).

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. In general, administration of factor IX 1 unit/kg will increase circulating factor IX levels by ~1% of normal.

General dosing for control or prevention of bleeding episodes or perioperative management: 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 = body weight (in kg) x desired Factor IX level increase (% or units/dL) x 1 unit/kg per units/dL

For example, for a 100% level in a 25 kg patient who has an actual level of 20%: Number of Factor IX Units needed = 25 kg x 80% x 1 unit/kg per units/dL = 2,000 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: Infants, Children, and Adolescents: The following recommendations reflect WFH guidelines 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 30 hours	1 to 2 days, may be longer if response is inadequate
Superficial muscle/no neurovascular compromise	40% to 60%	Every 12 to 30 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 30 hours	Initial: 1 to 2 days
	Maintenance: 30% to 60%	Every 12 to 30 hours	Maintenance: 3 to 5 days, sometimes longer as secondary prophylaxis during physiotherapy
CNS/Head	Initial: 60% to 80%	Every 12 to 30 hours	Initial: 1 to 7 days
CNS/Head	Maintenance: 30%	Every 12 to 30 hours	Maintenance: 8 to 21 days
Throat and neck	Initial: 60% to 80%	Every 12 to 30 hours	Initial: 1 to 7 days
Throat and neck	Maintenance: 30%	Every 12 to 30 hours	Maintenance: 8 to 14 days
Gastrointestinal	Initial: 60% to 80%	Every 12 to 30 hours	Initial: 7 to 14 days
Gastrointestinal	Maintenance: 30%	Every 12 to 30 hours	Maintenance: Not specified
Renal	40%	Every 12 to 30 hours	3 to 5 days
Deep laceration	40%	Every 12 to 30 hours	5 to 7 days
Surgery (major)	Preop: 60% to 80%	Single dose
	Postop: 40% to 60%	Every 12 to 30 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 30 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; Hoots 2003; Morfini 2008; Poon 2012; Prelog 2016; WFH [Srivastava 2020]). Evidence supporting the use of continuous infusion is primarily with Mononine (Hoots 2003).

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)

The median reported dose in postoperative patients (7 to 85 years) was 3.84 units/kg/hour (range: 1.74 to 7.3 units/kg/hour) (Hoots 2003).

Routine prophylaxis:

Note: Maintain factor IX trough levels >3% to 5% or higher as clinically indicated (WFH [Srivastava 2020]). 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.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined.

Cardiovascular: Flushing, thrombosis

Central nervous system: Burning sensation (in jaw/skull), chills, headache, lethargy, paresthesia, rigors

Dermatologic: Skin photosensitivity, urticaria

Gastrointestinal: Diarrhea, nausea, vomiting

Hematologic & oncologic: Disseminated intravascular coagulation

Hepatic: Increased serum alkaline phosphatase, increased serum ALT, increased serum AST

Hypersensitivity: Anaphylaxis, hypersensitivity reaction

Local: Discomfort at injection site (stinging, burning), injection site reaction, pain at injection site

Neuromuscular & skeletal: Neck tightness

Ophthalmic: Visual disturbance

Respiratory: Allergic rhinitis, asthma, laryngeal edema, pulmonary disease

Miscellaneous: Fever (including transient fever following rapid administration)

Postmarketing and/or case reports: Angioedema, cerebral hemorrhage (intrathalamic [Douvas, 2004]), cyanosis, decreased therapeutic response, dyspnea, factor IX inhibitor development, hypotension, myocardial infarction (high doses), pulmonary embolism (high doses), superior vena cava syndrome (neonates [Douvas, 2004])

Contraindications

AlphaNine SD: There are no contraindications listed in the manufacturer's labeling.

Mononine: Hypersensitivity to mouse protein

Immunine VH [Canadian product]: Hypersensitivity to factor IX or any component of the formulation; known allergy to heparin; history of heparin-induced thrombocytopenia; disseminated intravascular coagulation (DIC) and/or hyperfibrinolysis

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 and anaphylactic reactions have been reported with use. 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 may be associated with factor IX inhibitor development; patients experiencing allergic reactions should be evaluated for factor IX inhibitors (WFH [Srivastava 2020]).

• Thrombotic events: Observe closely for signs or symptoms of intravascular coagulation or thrombosis; risk is generally associated with the use of factor IX complex concentrates (containing therapeutic amounts of additional factors); however, potential risk exists with use of factor IX products (containing only factor IX). Use with caution when administering to patients with liver disease, postoperatively, neonates, or patients at risk of thromboembolic phenomena, disseminated intravascular coagulation or patients with signs of fibrinolysis due to the potential risk of thromboembolic complications.

Disease-related concerns:

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

Dosage form specific issues:

• Human plasma: Product of human plasma. Despite purification methods (AlphaNine SD - solvent detergent treated/virus filtered; Mononine - virus filtered); products may potentially contain infectious agents (eg, viruses, the variant Creutzfeldt-Jakob disease [vCJD] agent and, theoretically, the Creutzfeldt-Jakob disease [CJD] agent) that could transmit disease. Screening of donors, as well as testing and/or inactivation or removal of certain viruses, reduces the risk. Infections thought to be transmitted by this product should be reported to the manufacturer. Hepatitis A and B vaccination is recommended for all patients receiving plasma derivatives.

• 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:

• Appropriate use: Contains nondetectable levels of factors II, VII, and X. Therefore, NOT INDICATED for replacement therapy of any other clotting factor besides factor IX. In addition, factor IX concentrate is NOT INDICATED for reversal of anticoagulation due to either vitamin K antagonists or other anticoagulants (eg, dabigatran), hemophilia A patients with factor VIII inhibitors, or patients in a hemorrhagic state caused by reduced production of liver-dependent coagulation factors (eg, hepatitis, cirrhosis).

• 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.

• Immune tolerance induction: Safety and efficacy have not been established in immune tolerance induction with factor IX products. Nephrotic syndrome has occurred following immune tolerance induction in patients with factor IX inhibitors and a history of allergic reactions to therapy.

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. [DSC] = Discontinued product

Solution Reconstituted, Intravenous [preservative free]:

AlphaNine SD: 500 units (1 ea); 1000 units (1 ea); 1500 units (1 ea) [contains heparin, polysorbate 80]

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

Generic Equivalent Available: US

Pricing: US

Solution (reconstituted) (AlphaNine SD Intravenous)

500 unit (Price provided is per AHF Unit): $2.03

1000 unit (Price provided is per AHF Unit): $2.03

1500 unit (Price provided is per AHF Unit): $2.03

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.

Solution Reconstituted, Intravenous:

Immunine VH: 720 UNIT (1 ea)

Administration: Adult

IV intermittent bolus: IV administration only: Should be infused slowly over several minutes: Rate of administration should be determined by the response and comfort of the patient. Solution should be infused at room temperature.

AlphaNine SD: Administer IV at a rate not exceeding 10 mL/minute

Mononine: Administer IV at a rate of ~2 mL/minute (when reconstituted as directed to ~100 units/mL). Administration rates of up to 225 units/minute have been regularly tolerated without incident.

IV continuous infusion: Has also been 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; Holme 2018; Hoots 2003; Ménart 1998; Poon 2012; Rickard 1995; Schulman 1995; WFH [Srivastava 2020]).

Administration: Pediatric

Parenteral: IV administration only; plastic syringes are recommended for use with Mononine per the manufacturer; 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: Should be infused slowly over several minutes: Rate of administration should be determined by the response and comfort of the patient.

AlphaNine SD: Administer IV at a rate not exceeding 10 mL/minute.

Mononine: Administer IV at a rate of ~2 mL/minute. Administration rates of up to 225 units/minute have been regularly tolerated without incident (when reconstituted as directed to ~100 units/mL).

Continuous IV infusion: Limited data available. Evidence supporting the use of continuous infusion is primarily with Mononine. Continuous infusion may be administered either as the reconstituted solution or further diluted in NS; diluted solution should be prepared every 12 hours (Hoots 2003).

Use: Labeled Indications

Hemophilia B: Prevention and control of bleeding in patients with hemophilia B (congenital factor IX deficiency or Christmas disease).

Limitations of use: Contains nondetectable levels of factors II, VII, and X. Therefore, NOT INDICATED for replacement therapy of any other clotting factor besides factor IX or for reversal of anticoagulation due to either vitamin K antagonists or other anticoagulants (eg, dabigatran), for hemophilia A patients with factor VIII inhibitors, or for patients in a hemorrhagic state caused by reduced production of liver-dependent coagulation factors (eg, hepatitis, cirrhosis).

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 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]).

Monitoring Parameters

Monitoring assay selection: For plasma-derived factor IX products, the World Federation of Hemophilia recommends use of a one-stage or chromogenic factor IX activity assay calibrated with a plasma standard traceable to a World Health Organization international standard (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. Measurement of factor IX trough levels may aid in calculation of subsequent doses. The frequency of peak factor IX activity monitoring during active treatment depends on the indication, clinical response, and treatment day (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 BP 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)

Half-life elimination: IX component: ~21 to 25 hours

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AR) Argentina: Berinin p | Factor ix grifols | Immunine | Octanine f | Protromplex total tim 4 | Replenine vf;
(AT) Austria: Faktor ix | Haemonine;
(AU) Australia: Monofix | Tbsf high purity factor IX concentrate;
(BE) Belgium: Facteur ix conc. croix rouge | Factor ix solvent | Mononine | Nonafact;
(BG) Bulgaria: Aimafix di | Immunine | Octanine f | Prothromplex;
(BR) Brazil: Alphanine | Immunine | Mononine | Octanine f;
(CL) Chile: Alphanine | Octanine | Octanine f;
(CO) Colombia: Alphanine | Berinin p | Betafact | Haemonine | Immunine | Nanotiv | Octanine | Octanine f | Replenine vf;
(CZ) Czech Republic: Bebulin tim | Immunine | Mononine | Octanine f;
(DE) Germany: Alphanine | Berinin hs ix | Berinin p | Betafact | Haemonine | Immunine | Mononine | Octanine;
(EC) Ecuador: Immunine;
(EE) Estonia: Bebulin tim | Haemonine | Immunine | Octanine;
(EG) Egypt: Octanine;
(ES) Spain: Bebulin tim | Immunine stim plus | Mononine | Octanine | Proplex t;
(FI) Finland: Bemofil | F ix | Octanine;
(FR) France: Betafact | Mononine;
(GB) United Kingdom: Alphanine | Haemonine | Ht defix | Mononine | Prothromplex | Replenine vf;
(GR) Greece: Betafact | Mononine;
(HK) Hong Kong: Monofix-Vf;
(HR) Croatia: Nanotiv;
(HU) Hungary: Bebulin | Bebulin tim | Berinin p | Betafact | Immunine ix | Mononine | Octanine f;
(ID) Indonesia: Nonafact | Octanine f;
(IL) Israel: Mononine;
(IT) Italy: Aimafix di | Alphanine | Fixnove | Haemobionine | Immunine stim plus | Ixed | Mononine | Octanine;
(JP) Japan: Christmassin m | Novact | Novact m fujisawa | Novact-m;
(KR) Korea, Republic of: Facnyne;
(LT) Lithuania: Bebulin tim | Immunine | Octanine | Replenine vf;
(LU) Luxembourg: Mononine | Octanine;
(LV) Latvia: Bebulin tim | Haemonine | Octanine | Replenine faktor ix;
(MX) Mexico: Alphanine | Berinin p | Betafact | Immunine | Kedrifix | Octanine f | Replenine | Replenine vf;
(MY) Malaysia: Octanine f | Profilnine sd | Replenine vf;
(NL) Netherlands: Immunine | Immunonine;
(NO) Norway: Faktor IX nmd | Immunine | Nanotiv | Octanine f;
(PE) Peru: Octanine f | Replenine vf;
(PL) Poland: Immunine;
(PR) Puerto Rico: Alphanine sd | Bebulin | Bebulin vh | Mononine | Profilnine sd | Proplex t;
(PT) Portugal: Immunine | Mononine;
(PY) Paraguay: Berinin p | Factor ix grifols | Octanine f;
(RO) Romania: Immunine | Octanine f;
(RU) Russian Federation: Agemfil b | Immunine | Mononine | Octanine | Octanine f | Replenine | Replenine vf;
(SA) Saudi Arabia: Octanine | Preconativ | Replenine vf;
(SE) Sweden: Immunine | Mononine | Nanofix | Nanotiv;
(SK) Slovakia: Betafact | Immunine | Octanine f;
(TH) Thailand: Alphanine sd | Immunine | Profilnine sd;
(TN) Tunisia: Betafact | Haemonine | Immunine | Mononine;
(TR) Turkey: Berinin p | Betafact | Immunine | Nonafact | Octanine f | Replenine | Replenine vf;
(TW) Taiwan: High Purity Factor IX | Immunine;
(UA) Ukraine: Immunine | Octanine f;
(UY) Uruguay: Immunine;
(ZA) South Africa: Haemosolvate factor ix

Alade SL, Brown RE, Paquet A Jr. Polysorbate 80 and E-Ferol toxicity. Pediatrics. 1986;77(4):593-597. [PubMed 3960626]
AlphaNine SD (coagulation factor IX [human]) [prescribing information]. Los Angeles, CA: Grifols Biologicals LLC; March 2021.
Batorova A, Holme P, Gringeri A, et al; European Haemophilia Treatment Standardisation Board. Continuous infusion in haemophilia: current practice in Europe. Haemophilia. 2012;18(5):753-759. doi:10.1111/j.1365-2516.2012.02810.x [PubMed 22530687]
Batorova A, Martinowitz U. Continuous infusion of coagulation factors. Haemophilia. 2002;8(3):170-177. doi:10.1046/j.1365-2516.2002.00635.x [PubMed 12010406]
Centers for Disease Control (CDC). Unusual syndrome with fatalities among premature infants: association with a new intravenous vitamin E product. MMWR Morb Mortal Wkly Rep. 1984;33(14):198-199. http://www.cdc.gov/mmwr/preview/mmwrhtml/00000319.htm. [PubMed 6423951]
Chi C, Kadir RA. Inherited bleeding disorders in pregnancy. Best Pract Res Clin Obstet Gynaecol. 2012;26(1):103-117. [PubMed 22101176]
Douvas MG, Monahan PE. Life-threatening thrombosis complicating the management of hepatic hemorrhage: anticoagulant treatment in a newborn with hemophilia B. J Pediatr Hematol Oncol. 2004;26(4):258-263. [PubMed 15087956]
Holme PA, Tjønnfjord GE, Batorova A. Continuous infusion of coagulation factor concentrates during intensive treatment. Haemophilia. 2018;24(1):24-32 [PubMed 28873263]
Hoots WK, Leissinger C, Stabler S, et al. Continuous intravenous infusion of a plasma-derived factor IX concentrate (Mononine) in haemophilia B. Haemophilia. 2003;9(2):164-172. [PubMed 12614367]
Immunine VH (factor IX human) [product monograph]. Toronto, Ontario, Canada: Takeda Canada Inc; April 2023.
Isaksson M, Jansson L. Contact allergy to Tween 80 in an inhalation suspension. Contact Dermatitis. 2002;47(5):312-313. [PubMed 12534540]
Kadir R, Chi C, Bolton-Maggs P. Pregnancy and rare bleeding disorders. Haemophilia. 2009;15(5):990-1005. [PubMed 19298378]
Lee CA, Chi C, Pavord SR, et al. The obstetric and gynaecological management of women with inherited bleeding disorders-review with guidelines produced by a Taskforce of UK Haemophilia Centre Doctors' Organization. Haemophilia. 2006;12(4):301-336. [PubMed 16834731]
Lucente P, Iorizzo M, Pazzaglia M. Contact sensitivity to Tween 80 in a child. Contact Dermatitis. 2000;43(3):172. [PubMed 10985636]
Ménart C, Petit PY, Attali O, Massignon D, Dechavanne M, Négrier C. Efficacy and safety of continuous infusion of Mononine during five surgical procedures in three hemophilic patients. Am J Hematol. 1998;58(2):110-116. doi:10.1002/(sici)1096-8652(199806)58:2<110::aid-ajh4>3.0.co;2-v [PubMed 9625577]
Mononine (coagulation factor IX human) [prescribing information]. Kankakee, IL: CSL Behring LLC; December 2018.
Morfini M. Secondary prophylaxis with factor IX concentrates: continuous infusion. Blood Transfus. 2008;6(Suppl 2):21–25. [PubMed 19105506]
National Hemophilia Foundation (NHF). Medical and Scientific Advisory Council (MASAC) guidelines for perinatal management of women with bleeding disorders and carriers of hemophilia A and B (MASAC document 251). https://www.hemophilia.org/node/3660. Published September 17, 2017. Accessed June 7, 2018.
Pavord S, Rayment R, Madan B, et al; for the Royal College of Obstetricians and Gynaecologists. Management of inherited bleeding disorders in pregnancy: Green-top Guideline No. 71 (joint with UKHCDO). BJOG. 2017;124(8):e193–e263. doi: 10.1111/1471-0528.14592. [PubMed 28447403]
Poon MC, Card R. Hemophilia management in transfusion medicine. Transfus Apher Sci. 2012;46(3):299-307. doi:10.1016/j.transci.2012.03.020 [PubMed 22503305]
Prelog T, Dolničar MB, Kitanovski L. Low-dose continuous infusion of factor VIII in patients with haemophilia A. Blood Transfus. 2016;14(5):474‐480. [PubMed 26674820]
Rickard KA. Guidelines for therapy and optimal dosages of coagulation factors for treatment of bleeding and surgery in haemophilia. Haemophilia. 1995;1(suppl 1):8-13. doi:10.1111/j.1365-2516.1995.tb00104.x [PubMed 27214734]
Schulman S, Gitel S, Zivelin A, et al. The feasibility of using concentrates containing factor IX for continuous infusion. Haemophilia. 1995;1(2):103-110. doi:10.1111/j.1365-2516.1995.tb00048.x [PubMed 27214317]
Shelley WB, Talanin N, Shelley ED. Polysorbate 80 hypersensitivity. Lancet. 1995;345(8980):1312-1313. [PubMed 7746084]
Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al; Treatment Guidelines Working Group on Behalf of The World Federation of Hemophilia. Guidelines for the management of hemophilia. Haemophilia. 2013;19(1):e1-e47. doi:10.1111/j.1365-2516.2012.02909.x [PubMed 22776238]
Srivastava A, Santagostino E, Dougall A, et al; WFH Guidelines for the Management of Hemophilia panelists and co-authors. WFH guidelines for the management of hemophilia, 3rd edition. Haemophilia. 2020;26(suppl 6):1-158. doi:10.1111/hae.14046 [PubMed 32744769]
Varon D and Martinowitz U, "Continuous Infusion Therapy in Haemophilia," Haemophilia, 1998, 4(4):431-5. [PubMed 9873771]
White GC 2nd, Shapiro AD, Kurczynski EM, Kim HC, Bergman GE. Variability of in vivo recovery of factor IX after infusion of monoclonal antibody purified factor IX concentrates in patients with hemophilia B. The Mononine Study Group. Thromb Haemost. 1995;73(5):779-784. [PubMed 7482403]

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Factor IX, human plasma-derived: Drug information