Factor IX

Class: Hemostatics
VA Class: BL500
CAS Number: 37224-63-8
Brands: AlphaNine SD, Bebulin VH, Mononine, Profilnine SD

Introduction

Factor IX (human): Preparation of blood coagulation factor IX derived from pooled human plasma.^{149 151 152}

Factor IX complex (human): Prothrombin complex concentrate (PCC); preparation of nonactivated blood coagulation factors II, VII, IX, and X derived from pooled human plasma.^{100 140 e}

Uses for Factor IX

Hemophilia B

Factor IX (human)^{151 152} and factor IX complex (human; also known as PCC)^{100 140} are used for prevention and control of hemorrhagic episodes in patients with a deficiency of coagulation factor IX associated with hemophilia B (Christmas disease).^{100 140 151 152 156 e f}

In patients with preexisting thromboembolic risk factors, factor IX preferred over factor IX complex for treatment of hemophilia B.^{148 151 156 c f} (See Thromboembolic Events under Cautions.)

Factor IX (human), factor IX complex (human), and factor IX (recombinant) may be used in patients with hemophilia B; however, because of an increased risk of transmission of human viruses (e.g., HIV viruses, hepatitis A virus [HAV], hepatitis B virus [HBV], hepatitis C virus [HCV]) and other transmissible disease agents (e.g., agents for Creutzfeldt-Jakob disease [CJD], variant CJD [vCJD]) with plasma-derived factor IX preparations compared with factor IX (recombinant), the Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Foundation recommends factor IX (recombinant) as the preparation of choice for individuals with hemophilia B.^{155 156 j l} (See Risk of Transmissible Agents in Plasma-derived Preparations under Cautions.) Recombinant and plasma-derived preparations of factor IX produce comparable hemostatic effects.^{156 p}

Maintenance of hemostasis in patients with hemophilia B undergoing surgery.^{100 140 151 152 e f}

Also used for routine prophylaxis (i.e., administration at regular intervals) to reduce frequency of hemorrhagic events and preserve joint function.^{100 c e j l} MASAC and the World Federation of Hemophilia recommend primary prophylaxis for patients with severe hemophilia B (factor IX activity <1%) after careful consideration of risks versus benefits.^{c h}

Not indicated in the treatment of other coagulation factor deficiencies (e.g., factors II, VII, X).^{100 140 151 152}

Not indicated for the treatment^{151 152} or prevention ¹⁵² of hemophilia A in patients with inhibitors to factor VIII.^{151 152}

Not indicated in the treatment or reversal of coumarin-induced anticoagulation or hemorrhagic states caused by hepatitis-induced lack of production of liver-dependent coagulation factors.^{151 152}

Factor IX Dosage and Administration

General

• 
  

  Monitor factor IX frequently to individualize dosage and assess response to therapy.^{140 151 152} (See Laboratory Monitoring under Cautions.)

  
  

Administration

IV Administration

Administer factor IX (human) and factor IX complex (human) by slow IV injection or IV infusion.^{100 140 151 152}

Have been given as a continuous infusion†.^{c e f}

Manufacturers of Mononine and Profilnine SD recommend that drug be administered using plastic syringes only; factor IX (human) solution may adhere to glass.^{140 152}

Filter solution prior to administration.^{100 140 151 152 c}

Instructions on reconstitution, dilution, and administration vary according to preparation; consult manufacturer’s labeling for specific information on each factor IX (human) or factor IX complex (human) product.^{100 140 151 152}

Reconstitution

Prior to reconstitution of factor IX (human) and factor IX complex (human), allow injection concentrate and diluent to warm to room temperature (≤37°C).^{100 140 151 152}

Reconstitute factor IX (human) and factor IX complex (human) concentrates with diluent (sterile water for injection) provided by manufacturer.^{100 140 151 152}

Gently swirl solution to dissolve powder completely; do not shake.^{100 140 151 152}

Administer immediately or within 3 hours after reconstitution; discard any unused solution after 3 hours.^{100 140 151 152} Do not refrigerate reconstituted solutions.^{100 140 152 a}

Rate of Administration

Individualize infusion rates based on specific product and patient response and comfort.^{100 140 152} Administer slowly to avoid vasomotor reactions.^{140 151}

AlphaNine SD: Administer at a rate ≤10 mL/minute.¹⁵¹

Mononine: Administer solutions of 100 units/mL at a rate of approximately 2 mL/minute; has been administered at rates up to 225 units/minute without unusual adverse effects.^{152 a}

Bebulin VH: Administer at a rate ≤2 mL/minute.¹⁰⁰

Profilnine SD: Administer at a rate ≤10 mL/minute.¹⁴⁰

Dosage

Dosage (potency) of factor IX (human) and factor IX complex (human) expressed in terms of international units (IU, units) of factor IX activity.^{100 140 151 152 l} One unit is approximately equivalent to amount of factor IX activity in 1 mL of normal fresh pooled human plasma.^{100 140 151 152}

Individualize dosage and duration of therapy based on severity and location of hemorrhage, degree of factor IX deficiency, desired factor IX levels, presence of factor IX inhibitors, and clinical response.^{100 140 151 152 f n} (See Laboratory Monitoring under Cautions.)

Use the following calculations and dosage guidelines (based on the degree of hemorrhage or type of surgery) for administering the drug.^{100 140 151 152}

These calculations and suggested dosage regimens are only approximations and should not preclude appropriate laboratory determinations and individualization of dosage based on the hemostatic requirements of patients.^a The manufacturers’ dosage recommendations should be consulted for further information on dosage.^{100 140}

If calculated dosage is ineffective in achieving appropriate factor IX levels, consider the possibility that inhibitors to factor IX may have developed.^c Manufacturer of Mononine suggests that higher dosages may be required in such situations.¹⁵²

Administration of 1 unit/kg of AlphaNine SD, Mononine, or Profilnine SD generally increases factor IX activity by 1%.^{140 151 152} Administration of 1 unit/kg of Bebulin VH generally increases factor IX activity by 0.8%.¹⁰⁰

Use the following formula for AlphaNine SD, Mononine, or Profilnine SD to determine dose of factor IX (human) or factor IX complex (human) required to achieve a particular percentage increase in plasma factor IX level:^{140 151 152}

Units required = body weight (in kg) × 1 (unit/kg) × desired factor IX increase (in % of normal)

Calculate dosages of Bebulin VH using the following formula:¹⁰⁰

Units required = body weight (in kg) × 1.2 (unit/kg) × desired factor IX increase (in % of normal)

Pediatric Patients

Hemophilia B

AlphaNineSD (Factor IX [human])

IV

Pediatric patients >16 years of age with minor hemorrhage (e.g., bruises, cuts, scrapes, uncomplicated joint hemorrhage): 20–30 units/kg twice daily to achieve a plasma factor IX level of at least 20–30% of normal until bleeding resolves or healing occurs, usually 1–2 days.¹⁵¹

Pediatric patients >16 years of age with moderate hemorrhage (e.g., epistaxis, mouth and gum bleeding, tooth extraction, hematuria): 25–50 units/kg twice daily to achieve a plasma factor IX level of 25–50% of normal until healing occurs, average 2–7 days.¹⁵¹

Pediatric patients >16 years of age with major hemorrhage (e.g., joint or muscle bleeding [especially in large muscles], major trauma, hematuria, intracranial bleeding, intraperitoneal bleeding): Initially, 30–50 units/kg twice daily to achieve a plasma factor IX level of 50% of normal for at least 3–5 days.¹⁵¹ Use additional doses of 20 units/kg twice daily to maintain a plasma factor IX level of 20% of normal until healing occurs.¹⁵¹ Up to 10 days of treatment may be necessary.¹⁵¹

Pediatric patients >16 years of age undergoing surgery: Initially, 50–100 units/kg twice daily to achieve a plasma factor IX level of 50–100% of normal prior to surgery.¹⁵¹ Use additional doses of 50–100 units/kg twice daily for 7–10 days (or until healing achieved) to maintain factor IX levels of 50–100% of normal.¹⁵¹

Mononine (Factor IX [human])

IV

Minor (spontaneous) hemorrhage or prophylaxis: Initially, up to 20–30 units/kg to achieve a plasma factor IX level of 15–25% of normal; repeat once at 24 hours, if necessary.¹⁵²

Major trauma: Initially, up to 75 units/kg every 18–30 hours to achieve a plasma factor IX level of 25–50% of normal.¹⁵² Up to 10 days of treatment may be necessary, depending on severity of bleeding.¹⁵²

Surgery: Initially, up to 75 units/kg every 18–30 hours to achieve a plasma factor IX level of 25–50% of normal.¹⁵² Up to 10 days of treatment may be necessary.¹⁵²

Profilnine SD (Factor IX Complex [human])

IV

Pediatric patients >16 years of age with mild to moderate hemorrhage: Use appropriate dosage to achieve a plasma factor IX level of 20–30% of normal; single administration usually sufficient.¹⁴⁰

Pediatric patients >16 years of age with severe hemorrhage: Use appropriate dosage to achieve a plasma factor IX level of 30–50% of normal; daily infusions usually required.¹⁴⁰

Pediatric patients >16 years of age undergoing surgery: Use appropriate dosage to achieve a plasma factor IX level of approximately 30–50% of normal for at least 1 week following procedure.¹⁴⁰

Pediatric patients >16 years of age undergoing tooth extractions: Use appropriate dosage to achieve a plasma factor IX level of 50% of normal prior to procedure; may give additional doses if bleeding recurs.¹⁴⁰

Prophylaxis

IV

Optimum dosage regimen not yet established; individualize dosage.^{c l}

Adults

Hemophilia B

AlphaNineSD (Factor IX [human])

IV

Minor hemorrhage (e.g., bruises, cuts, scrapes, uncomplicated joint hemorrhage): 20–30 units/kg twice daily to achieve a plasma factor IX level of at least 20–30% of normal until bleeding resolves or healing occurs, usually 1–2 days.¹⁵¹

Moderate hemorrhage (e.g., epistaxis, mouth and gum bleeding, tooth extraction, hematuria): 25–50 units/kg twice daily to achieve a plasma factor IX level of 25–50% of normal until healing occurs, average 2–7 days.¹⁵¹

Major hemorrhage (e.g., joint or muscle bleeding [especially in large muscles], major trauma, hematuria, intracranial bleeding, intraperitoneal bleeding): Initially, 30–50 units/kg twice daily to achieve a plasma factor IX level of 50% of normal for at least 3–5 days.¹⁵¹ Use additional doses of 20 units/kg twice daily to maintain a plasma factor IX level of 20% of normal until healing occurs.¹⁵¹ Up to 10 days of treatment may be necessary.¹⁵¹

Surgery: Initially, 50–100 units/kg twice daily to achieve a plasma factor IX level of 50–100% of normal prior to surgery.¹⁵¹ Use additional doses of 50–100 units/kg twice daily for 7–10 days (or until healing achieved) to maintain a factor IX level of 50–100% of normal.¹⁵¹

Mononine (Factor IX [human])

IV

Minor (spontaneous) hemorrhage or prophylaxis: Initially, up to 20–30 units/kg to achieve a plasma factor IX level of 15–25% of normal; repeat once at 24 hours, if necessary.¹⁵²

Major trauma: Initially, up to 75 units/kg every 18–30 hours to achieve a plasma factor IX level of 25–50% of normal.¹⁵² Up to 10 days of treatment may be necessary, depending on severity of bleeding.¹⁵²

Surgery: Initially, up to 75 units/kg every 18–30 hours to achieve a plasma factor IX level of 25–50% of normal.¹⁵² Up to 10 days of treatment may be necessary.¹⁵²

BebulinVH (Factor IX Complex [human])

IV

Minor hemorrhage (e.g., early hemarthrosis, minor epistaxis, gingival bleeding, mild hematuria): Initially, 25–35 units/kg to achieve a plasma factor IX level of 20% of normal.¹⁰⁰ Single administration usually sufficient; may repeat once after 24 hours, if necessary.¹⁰⁰

Moderate hemorrhage (e.g., severe joint bleeding, early hematoma, major open bleeding, minor trauma, minor hemoptysis, minor hematemesis, minor melena, major hematuria): Initially, 40–55 units/kg to achieve a plasma factor IX level of approximately 40% of normal; may repeat every 24 hours for 2 days or until adequate healing occurs.¹⁰⁰

Major hemorrhage (e.g., severe hematoma, major trauma, severe hemoptysis, severe hematemesis, severe melena): Initially, 60–70 units/kg to achieve a plasma factor IX level of ≥60% of normal, unless patient has a high risk for thrombosis.¹⁰⁰ (See Thromboembolic Events under Cautions.) May repeat every 24 hours for 2–3 days or until adequate healing occurs.¹⁰⁰

Minor surgery (e.g., tooth extraction): Initially 50–60 units/kg to achieve a plasma factor IX level of approximately 40–60% of normal 1 hour prior to surgery.¹⁰⁰ One dose is usually sufficient for single tooth extraction.¹⁰⁰ For extraction of several teeth and other minor surgical procedures, use additional doses of 25–55 units/kg for 1–2 weeks after surgery to maintain a plasma factor IX level of approximately 20–40% of normal.¹⁰⁰ More frequent (e.g., every 12 hours) dosing may be required for initial treatments, while longer intervals (e.g., every 24 hours) usually sufficient during later postoperative period.¹⁰⁰

Major surgery: Initially, 70–95 units/kg to achieve a plasma factor IX level of ≥60% of normal 1 hour prior to surgery, unless patient has a high risk for thrombosis.¹⁰⁰ (See Thromboembolic Events under Cautions.) Use additional doses of 35–70 units/kg for 1–2 weeks postoperatively to maintain a plasma factor IX level of approximately 20–60% of normal, then 25–35 units/kg from week 3 onward to maintain a plasma factor IX level of approximately 20% of normal.¹⁰⁰ More frequent (e.g., every 12 hours) dosing may be required for initial treatments, while longer intervals (e.g., every 24 hours) usually sufficient during later postoperative period.¹⁰⁰

Profilnine SD (Factor IX Complex [human])

IV

Mild to moderate hemorrhage: Use appropriate dosage to achieve a plasma factor IX level of 20–30% of normal; single administration usually sufficient.¹⁴⁰

Severe hemorrhage: Use appropriate dosage to achieve a plasma factor IX level of 30–50% of normal; daily infusions usually required.¹⁴⁰

Surgery: Use appropriate dosage to achieve a plasma factor IX level of approximately 30–50% of normal for at least 1 week following surgery.¹⁴⁰

Tooth extractions: Use appropriate dosage to achieve a factor IX level of 50% of normal prior to procedure; may give additional doses if bleeding recurs.¹⁴⁰

Prophylaxis

IV

Optimum dosage regimen not yet established; individualize dosage.^{100 c l}

Prescribing Limits

Pediatric Patients

Hemophilia B

IV

AlphaNine SD (pediatric patients >16 years of age), ProfilnineSD (pediatric patients >16 years of age): Maximum rate of infusion 10 mL/minute.^{140 151}

Mononine: Infusion rates up to 225 units/minute have been well-tolerated.¹⁵²

Adults

Hemophilia B

IV

AlphaNine SD, ProfilnineSD: Maximum rate of infusion 10 mL/minute.^{140 151}

Bebulin VH: Maximum rate of infusion 2 mL/minute.¹⁰⁰

Mononine: Infusion rates up to 225 units/minute have been well-tolerated.¹⁵²

Cautions for Factor IX

Contraindications

• 
  

  Known hypersensitivity to murine protein (Mononine).¹⁵²

  
  

Warnings/Precautions

Warnings

Risk of Transmissible Agents in Plasma-derived Preparations

Potential vehicle for transmission of human viruses (e.g., HIV, HAV, HBV, HCV) and other infectious agents.^{100 140 151 152 155 156}

Improved donor screening, viral-inactivating procedures (e.g., solvent/detergent, heat-treatment) and/or immunoaffinity chromatography procedures have reduced but not completely eliminated risk of pathogen transmission with plasma-derived factor IX and factor IX complex preparations.^{100 130 140 151 152 155 156 l}

Possibility still exists for transmission of human viruses (e.g., HIV, HAV, HBV, HCV) and other infectious agents (e.g., unknown viruses; other disease agents including transfusion-transmitted virus [TTV], CJD, vCJD, transmissible spongiform encephalopathy [TSE] diseases).^{100 130 140 145 146 147 151 152 155 156 161 162}

Current viral-depleting methods apparently can inactivate lipid-encapsulated viruses, such as HBV, HIV-1, HIV-2, and HCV; however, these methods are less effective against viruses that do not have a lipid envelope, such as parvovirus B19¹⁵⁶ and HAV.^{155 156} Transmission of nonenveloped viruses, including HAV^{156 157} and parvovirus B19,¹⁵⁶ has been documented following administration of plasma-derived coagulation factors.^{151 152 156 d n} Monitor for signs and symptoms of parvovirus B19 and hepatitis A during therapy.^{100 152} (See Advice to Patients.)

Carefully weigh risk of pathogen transmission versus benefits of factor IX (human) and factor IX complex (human) prior to initiating therapy.^{100 140 151 152 155}

Report any infections thought to be associated with factor IX (human) or factor IX complex (human) to the manufacturer, FDA, and CDC.^{100 140 151 152 156}

Risk of Hepatitis

Risk of hepatitis A or hepatitis B infection.^{100 140 151 152 156 j}

Monitor closely for signs and symptoms of hepatitis A during therapy.^{100 152} (See Advice to Patients.)

MASAC and other experts recommend administration of hepatitis B vaccine to all individuals with a bleeding disorder at birth or at time of diagnosis.^{100 140 141 151 156 160 j l} CDC recommends immunization with hepatitis A vaccine for all patients ≥12 months of age with a bleeding disorder.^b

Risk of HIV Infection

Potential vehicle for transmission of HIV.^{101 102 103 105 106 105 106 111 121 126 127 128 132 133 135 138 140 151} HIV seroconversion reported in the past in patients who received factor IX complex (human) from donors not screened for HIV and/or prepared using suboptimal viral-inactivating procedures (e.g., heat-treatment only).^{101 102 103 108 121 125 128 129 131 136 137 138 j}

No reports to date of HIV transmission with currently available plasma-derived clotting factor preparations.^{151 152 156 j}

Risk of Creutzfeldt-Jakob Disease

Theoretic possibility of transmitting causative agent of CJD or vCJD.^{140 145 152 155 d j} Several probable cases of vCJD transmission reported from transfusion of human RBCs.^{155 167} However, no reports to date of CJD or vCJD transmission from commercially available factor IX products.^{145 146 155} For further information on CJD and vCJD precautions related to blood and blood products, consult the FDA’s guidance for industry ().¹⁴⁵

Risk of West Nile Virus

Evidence of West Nile virus (WNV) transmission through transplanted organs (e.g., heart, liver, kidney) and blood products.^{153 154 163 164} However, WNV transmission through commercially available factor IX preparations unlikely due to current viral-inactivating procedures.^{143 154}

For further information on WNV precautions related to blood and blood products, consult the FDA’s guidance for industry ().¹⁵⁴

Thromboembolic Events

Serious and potentially fatal thromboembolic events (e.g., MI, venous thrombosis, PE, disseminated intravascular coagulopathy [DIC]) reported with use of factor IX complex preparations.^{140 151 152 f g} Increased risk in patients with preexisting thrombotic risk factors (e.g., liver disease, concomitant use of thrombogenic drugs, history of thrombosis, DIC) and in those receiving prolonged therapy and/or high dosages of factor IX complex; also increased risk during postoperative period in patients undergoing surgery, and in neonates.^{100 140 152 f g} Exercise caution when factor IX (human) or factor IX complex (human) is used in such patients.¹⁵²

Weigh potential benefits of drug against risks of thrombotic complications.^{140 152 a} Consider using pure factor IX preparations that may be less thrombogenic than factor IX complex in high-risk patients.^{148 151 152 156 c f l} Patients undergoing surgery and those with other predisposing risk factors should be monitored closely for manifestations of thromboembolism (e.g., changes in BP or pulse rate, respiratory distress, chest pain, cough) and DIC.^{100 140 151} Follow recommended dosage guidelines to decrease risk of thromboembolic complications;¹⁵¹ one manufacturer suggests that in high-risk patients, factor IX levels not exceed 60%.¹⁰⁰ If evidence of thrombosis or DIC occurs during therapy, discontinue factor IX complex immediately.¹⁰⁰

Renal Effects

Nephrotic syndrome reported in patients undergoing immune tolerance induction who have inhibitors and/or a history of hypersensitivity reactions to factor IX.^{151 152 d j k l} Safety and efficacy of factor IX products for immune tolerance induction not established.^{151 152}

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (hives, pruritus, edema, tightness of chest, angioedema, dyspnea, wheezing, faintness, hypotension, tachycardia, urticaria, shock) reported with use of all factor IX products.^{100 151 152 d}

Increased risk in patients with certain genetic mutations of factor IX and those with inhibitors to factor IX.^{151 152 c d j k l m} Up to 50% of patients with inhibitors to factor IX may experience severe hypersensitivity reactions, including anaphylaxis.^c

In patients with inhibitors or with known genetic defects associated with inhibitor development, administer initial (e.g., approximately 10–20) infusions in a hospital setting where severe allergic reactions can be managed.^{c j k}

Closely observe for hypersensitivity reactions, especially during the initial phases of therapy.^{151 152}

If manifestations of hypersensitivity reactions or anaphylaxis occur, discontinue drug immediately and initiate appropriate therapy.^{100 140 151 152} Depending on severity of the reaction, use antihistamines, slow infusion rate, or switch to another factor IX product.^{100 140 151 152 c}

Antibody Formation

Mononine contains trace amounts of murine protein which may stimulate antibody latex insert production and cause hypersensitivity reactions.¹⁵² (See Contraindications under Cautions.)

General Precautions

Development of Inhibitors to Factor IX

Risk for development of inhibitors (IgG antibodies) to factor IX following treatment with factor IX preparations.^{c j k l m} Reported in about 1–5% of patients with hemophilia B, usually within the first 10–20 days of treatment.^{c e j m} Patients with certain genetic mutations of the factor IX gene may be at higher risk.^{152 c j k l m}

Consultation with a hemophilia treatment center strongly recommended for patients with inhibitors.^{156 c}

Laboratory Monitoring

Monitor factor IX levels at regular intervals (at least daily) to guide dosing and ensure adequate therapeutic response.^{100 140 151 152 c n}

Monitor for development of inhibitors during treatment and prior to surgery.^c (See Development of Inhibitors to Factor IX under Cautions.)

Specific Populations

Pregnancy

Category C.^{100 140 151 152}

Lactation

Not known whether factor IX (human) or factor IX complex (human) is distributed into human milk.^{i o}

Pediatric Use

Use with caution in neonates because of potential thrombotic risk.¹⁵² (See Thromboembolic Events under Cautions.)

AlphaNine SD: Safety and efficacy not established in children ≤16 years of age.¹⁵¹ In a well-controlled clinical study in patients who previously received factor IX concentrates for hemophilia B, and in an ongoing safety and efficacy clinical trial in patients who did not previously receive factor IX concentrates, pediatric patients responded similarly to adult patients;¹⁵¹ adverse effects in these children were similar to those observed in patients >16 years of age.¹⁵¹

Bebulin VH: Safety and efficacy not established; studies evaluating use in pediatric patients with hemophilia B not available.ⁱ

Mononine: Safety and efficacy established in pediatric patients between the ages of 1 day and 20 years; excellent hemostasis achieved with no thrombotic complications.¹⁵² Dosing in children is generally based on the same guidelines as for adults.¹⁵²

Profilnine SD: Safety and efficacy not established in children ≤16 years of age.¹⁴⁰ In a well-controlled clinical study in patients who previously received factor IX complex for hemophilia B, pediatric patients responded similarly to adult patients; no adverse effects were reported in children.¹⁴⁰

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.¹⁵² Select dosage with caution.¹⁵²

Common Adverse Effects

Fever,^{100 140 152} chills,^{140 151 152} nausea,^{100 140 151 152} vomiting,^{100 140 152} headache,^{140 152} somnolence,¹⁴⁰ lethargy,^{140 152} flushing,^{140 152} tingling,^{140 152} stinging or burning at infusion site.¹⁵²

Interactions for Factor IX

Specific Drugs

Drug	Interaction	Comments
Antifibrinolytics (e.g., tranexamic acid, aminocaproic acid)	Potential additive thrombotic effects and increased risk for thrombosis with factor IX complex preparationsc	Avoid concomitant usec

Factor IX Pharmacokinetics

Absorption

Plasma Concentrations

Following IV infusion over 5–15 minutes, plasma concentrations of factor IX increase by approximately 0.01–0.014 units/mL per unit/kg administered.^e

Distribution

Extent

Readily diffuses through interstitial fluid; distributes through both intravascular and extravascular compartments.^{e f m}

Circulates in plasma as unbound drug.^e

Binds rapidly and reversibly to vascular endothelium.^e

Not known whether factor IX (human) and factor IX complex (human) are distributed into milk.^{i o}

Elimination

Half-life

Biphasic.^{a e}

Half-life subject to interindividual variation; approximately 18–25 hours for factor IX,^{151 152 c j} and 18–36 hours for factor IX complex.^{100 140 151}

Factor IX complex (human) is rapidly cleared from plasma.^a

Stability

Storage

Parenteral

Powder for Injection

AlphaNine SD: 2–8°C (avoid freezing to prevent damage to the diluent vial); may store at room temperature ≤30°C for up to 1 month.¹⁵¹ Use solution within 3 hours of reconstitution.¹⁵¹

Bebulin VH: 2–8°C (avoid freezing to prevent damage to the diluent vial).¹⁰⁰ Do not use beyond expiration date.¹⁰⁰ Do not refrigerate after reconstitution; use solution within 3 hours of reconstitution.¹⁰⁰

Mononine: 2–8°C (avoid freezing to prevent damage to the diluent vial); may store at room temperature ≤25°C for up to 1 month.¹⁵² Do not use beyond expiration date.¹⁵² Do not refrigerate after reconstitution; use solution within 3 hours of reconstitution.¹⁵²

Profilnine SD: 2–8°C (avoid freezing to prevent damage to the diluent vial); may store at room temperature ≤30°C for up to 3 months.¹⁴⁰ Use solution within 3 hours of reconstitution.¹⁴⁰

ActionsActions

• 
  

  Factor IX is a vitamin K-dependent coagulation factor synthesized in the liver.¹⁵²

  
  


• 
  

  Factor IX is essential for blood clotting and maintenance of hemostasis.^{152 f j}

  
  


• 
  

  Patients with hemophilia B (Christmas disease) have decreased levels of endogenous factor IX, resulting in a hemorrhagic tendency and clinical manifestations such as bleeding into soft tissues, muscles, joints, and internal organs.^{152 c}

  
  


• 
  

  Clinical severity and frequency of bleeding in patients with hemophilia B correlate with the degree of deficiency of factor IX activity.^c Patients with mild hemophilia B generally have >5% of normal activity, those with moderate disease generally have 1–5% of normal activity, and those with severe disease have <1% of normal activity.^{c d f j l}

  
  


• 
  

  Administration of factor IX (human) to patients with hemophilia B results in increased plasma levels of factor IX and temporarily corrects coagulation defect.¹⁵²

  
  


• 
  

  Factor IX is activated by Factor XIa in the intrinsic coagulation pathway.¹⁵² Activated factor IX, in combination with activated factor VIII, activates factor X to Xa, resulting ultimately in the conversion of factor II (prothrombin) to thrombin and formation of a fibrin clot.^{152 f}

  
  


• 
  

  Factor IX (human) preparations are purified concentrates of factor IX derived from human plasma.^{151 152} Factor IX complex (human) preparations contain variable amounts of vitamin K-dependent clotting factors II, VII, IX, and X.^{100 140 e f}

  
  


• 
  

  Prepared using different methods (e.g., precipitation, gel filtration, chromatography, ultrafiltration) to isolate and purify factor IX.^{100 140 151 152 l} Undergoes viral inactivation processes (e.g., heat, solvent/detergent) to reduce risk of viral transmission.^{100 140 151 152 156 l}

  
  

Advice to Patients

• 
  

  Importance of discontinuing therapy and immediately informing clinician if fever, rash, urticaria, nausea, vomiting, or other manifestations of hypersensitivity reactions or anaphylaxis occur or, alternatively, seeking immediate emergency care depending on severity of such reactions.^{100 140 151 152}

  
  


• 
  

  Risk of transmission of parvovirus B19 and/or hepatitis A from plasma-derived factor IX (human) and factor IX complex (human).^{100 140 151 152} Importance of informing clinician promptly if symptoms of potential parvovirus B19 infection (fever, drowsiness, chills and rhinorrhea followed by rash and joint pain 2 weeks later) or hepatitis A infection (low-grade fever, anorexia, nausea, vomiting, fatigue, jaundice, dark urine, abdominal pain) occur.^{100 152}

  
  


• 
  

  Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., liver disease).^{100 140 151 152}