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Factor IX (Human), Factor IX Complex (Human)

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): Preparation of nonactivated blood coagulation factors II, VII, IX, and X derived from pooled human plasma; also known as a 3-factor prothrombin complex concentrate (PCC).100 140 173 174 188

Uses for Factor IX (Human), Factor IX Complex (Human)

Hemophilia B

Prevention and control of hemorrhagic episodes in patients with a deficiency of coagulation factor IX associated with hemophilia B (Christmas disease).100 140 151 152 156 173 174

Maintenance of hemostasis in patients with hemophilia B undergoing surgery.100 140 151 152 173 174

In patients with preexisting thromboembolic risk factors, pure factor IX preparations are preferred over factor IX complex for treatment of hemophilia B.148 151 156 171 174 (See Thromboembolic Events under Cautions.)

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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.155 156 178 180 (See Risk of Transmissible Agents in Plasma-derived Preparations under Cautions.) Recombinant and plasma-derived preparations of factor IX are similar and produce comparable hemostatic effects.156 184

Also used for routine prophylaxis (i.e., administration at regular intervals) to prevent or reduce frequency of hemorrhagic events and preserve joint function.100 171 173 176 178 180 185 186 MASAC recommends prophylaxis in patients with severe hemophilia B (factor IX activity <1%) after careful consideration of risks versus benefits.176

Not indicated for treatment of other coagulation factor deficiencies (e.g., factors II, VII, X) or for management of hemophilia A patients with inhibitors.100 140 151 152

Not indicated for 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 (Human), Factor IX Complex (Human) Dosage and Administration

General

  • Monitor factor IX levels 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 by continuous infusion.171 173 174

Some manufacturers recommend that factor IX preparations be administered using plastic syringes only since such solutions may adhere to glass.140 152

Filter solution prior to administration.100 140 151 152 171

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) preparation.100 140 151 152

Reconstitution

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

Reconstitute injection 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

Rate of Administration

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

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

Mononine: Administer solutions containing 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

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.100 140 151 152 180 One unit is approximately equivalent to amount of factor IX activity in 1 mL of pooled normal 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, and clinical response.100 140 151 152 174 (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 doses are only approximations and should not preclude appropriate laboratory determinations and individualization of dosage based on the hemostatic requirements of patients.100 140 151 152 a The manufacturers’ dosage recommendations should be consulted for further information on dosage.100 140 151 152

If calculated dosage is ineffective in achieving appropriate factor IX levels, consider the possibility that inhibitors to factor IX may have developed.171 Manufacturer of Mononine suggests that higher dosages may be required in such situations;152 however, caution is advised when administering higher than recommended doses.151 (See Thromboembolic Events under Cautions.)

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

Calculate dosage of AlphaNine SD, Mononine, or Profilnine SD using the following formula :140 151 152

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

Calculate dosage 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 Administer additional doses of 20 units/kg twice daily to maintain plasma factor IX levels 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 Administer 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: Administer 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: Administer 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: Administer 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: Administer appropriate dosage to achieve a plasma factor IX level of 50% of normal prior to procedure; may give additional doses if bleeding recurs.140

Routine Prophylaxis
IV

Various dosing regimens have been recommended; optimal dosage remains to be established.100 171 173 176 185 186 Dosages of 25–40 units/kg twice a week commonly recommended.171 173 185 186 Evaluate patients periodically to determine continued need for prophylaxis.100 171

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 Administer 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 Administer 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, administer additional doses of 25–55 units/kg for 1–2 weeks after surgery to maintain plasma factor IX levels 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.) Administer 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 plasma factor IX levels 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: Administer appropriate dosage to achieve a plasma factor IX level of 20–30% of normal; single administration usually sufficient.140

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

Surgery: Administer 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: Administer appropriate dosage to achieve factor IX levels of 50% of normal prior to procedure; may give additional doses if bleeding recurs.140

Routine Prophylaxis
IV

Various dosing regimens have been recommended; optimal dosage remains to be established.100 171 173 176 185 186 Dosages of 25–40 units/kg twice a week commonly recommended.171 173 185 186 Manufacturer of Bebulin VH states that prophylactic dosages of 20–30 units/kg administered once or twice weekly have been shown to substantially reduce frequency of spontaneous hemorrhage.100 Individualize prophylactic dosing regimens and evaluate patients periodically to determine continued need for prophylaxis.100 171

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 (Human), Factor IX Complex (Human)

Contraindications

  • Known hypersensitivity to murine protein (Mononine).152

Warnings/Precautions

Warnings

Risk of Transmissible Agents in Plasma-derived Preparations

Possibility 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

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.100 130 140 151 152 155 156 180

Current viral-depleting methods can inactivate lipid-encapsulated viruses, such as HBV, HIV-1, HIV-2, and HCV, but are less effective against viruses (e.g.,parrovirus B19, HAV) that do not have a lipid envelope.155 156 Transmission of nonenveloped viruses, including HAV156 157 and parvovirus B19,156 has been documented following administration of plasma-derived coagulation factors.151 152 156 172 182 Monitor for signs and symptoms of parvovirus B19 and hepatitis A infection during therapy.100 152 (See Advice to Patients.)

Carefully weigh risk of pathogen transmission versus benefits of 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.100 140 151 152 156 178

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

Hepatitis B vaccine is recommended in all individuals with a bleeding disorder at birth or at time of diagnosis.100 140 141 151 156 160 178 180 Immunization with hepatitis A vaccine is recommended for all individuals ≥1 year of age with hemophilia or other congenital bleeding disorders.156 170

Individuals receiving blood or plasma infusions may develop signs and symptoms of other viral infections, particularly non-A or non-B hepatitis.100 152

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 previously 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).101 102 103 108 121 125 128 129 131 136 137 138 178

No reports to date of HIV transmission with currently available plasma-derived clotting factor preparations.151 152 156 178

Risk of Creutzfeldt-Jakob Disease

Theoretic possibility of transmitting causative agent of CJD or vCJD.140 145 151 152 155 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 Infection

Evidence of West Nile virus (WNV) transmission through transplanted organs (e.g., heart, liver, kidney) and blood products.143 153 154 163 164 However, WNV transmission through commercially available factor IX preparations unlikely due to current viral-inactivating procedures.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 coagulation [DIC]) reported with use of factor IX (human)151 152 and factor IX complex (human) preparations.140 174 175 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.100 140 152 174 175 Exercise caution when factor IX (human) or factor IX complex (human) is used in such patients.152

Weigh potential benefits of the drug against risks of thrombotic complications.140 152 Consider using pure factor IX preparations that may be less thrombogenic than factor IX complex in high-risk patients.148 151 152 156 171 174 180 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.151 152 172 178 179 180 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.100 151 152 172

Increased risk in patients with certain genetic mutations of factor IX and those with inhibitors to factor IX.151 152 171 172 178 179 180 181 (See Development of Inhibitors to Factor IX under Cautions.) Up to 50% of patients with inhibitors to factor IX may experience severe hypersensitivity reactions, including anaphylaxis.171

In patients with inhibitors or with known genetic defects associated with inhibitor development, administer initial (e.g., approximately 10–20) infusions of factor IX concentrates in a hospital setting where severe allergic reactions can be managed.171 179 180

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, administer antihistamines, slow infusion rate, or switch to another factor IX product.100 140 151 152 171

Antibody Formation to Trace Animal Proteins

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

Latex Sensitivity

Packaging components of Bebulin VH may contain natural latex proteins;100 take appropriate precautions if injection is handled by or administered to individuals with a history of natural latex sensitivity.189 190

General Precautions

Development of Inhibitors to Factor IX

Risk for development of inhibitors (IgG antibodies) to factor IX following treatment with factor IX preparations.171 178 179 180 181 Reported in about 1–5% of patients with hemophilia B, usually within the first 10–20 days of treatment.171 173 178 181 Patients with certain genetic mutations of the factor IX gene may be at higher risk of inhibitor development and of experiencing a hypersensitivity reaction.152 171 178 179 180 181 (See Hypersensitivity Reactions under Cautions.)

Consultation with a hemophilia treatment center strongly recommended for patients with inhibitors.156 171

Laboratory Monitoring

Monitor factor IX levels at regular intervals (at least daily) to guide dosing and ensure adequate therapeutic response.100 140 151 152 171 182

Monitor for development of inhibitors during treatment and prior to surgery.171 (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.177 183

Pediatric Use

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

AlphaNine SD: Safety and efficacy not established in children ≤16 years of age.151 In a few studies that included pediatric patients, adverse effects in 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.177

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 clinical study in patients who previously received factor IX concentrates for hemophilia B, the 2 pediatric patients who received factor IX complex (human) responded similarly to adults and no adverse effects were reported.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 dyspnea,151 152 tingling,140 152 stinging or burning at infusion site.152

Interactions for Factor IX (Human), Factor IX Complex (Human)

Specific Drugs

Drug

Interaction

Comments

Antifibrinolytics (e.g., tranexamic acid, aminocaproic acid)

Potential additive thrombotic effects and increased risk of thrombosis with factor IX complex preparations171

Avoid concomitant use171

Factor IX (Human), Factor IX Complex (Human) 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.173

Distribution

Extent

Readily diffuses through interstitial fluid; distributes through both intravascular and extravascular compartments.173 174 181

Circulates in plasma as a free molecule.173

Binds rapidly and reversibly to vascular endothelium.173

Not known whether factor IX (human) and factor IX complex (human) are distributed into milk.177 183

Elimination

Half-life

Biphasic.173 a

Half-life subject to interindividual variation; approximately 18–25 hours for factor IX,151 152 171 178 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 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 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

Actions

  • 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.152 174 178

  • 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.152 171

  • Clinical severity and frequency of bleeding in patients with hemophilia B correlate with the degree of deficiency of factor IX activity.171 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.171 172 174 178 180

  • 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.152 174

  • 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.100 140 173 174

  • Different methods (e.g., precipitation, gel filtration, chromatography, ultrafiltration) are used to isolate and purify factor IX.100 140 151 152 180 Undergoes viral inactivation processes (e.g., heat, solvent/detergent) to reduce risk of viral transmission.100 140 151 152 156 180

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

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.100 140 151 152 177

  • Importance of informing patients of other important precautionary information.100 140 151 152 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Factor IX (Human)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV use only

number of units indicated on label

AlphaNine SD (with sterile water for injection diluent; solvent/detergent-inactivated, column chromatograph purified; and virus filtered; available with transfer needle and microaggregate filter)

Grifols

Mononine (with sterile water for injection diluent; monoclonal antibody purified; available with alcohol swabs, transfer needle, filter spike, and an administration set)

CSL Behring

Factor IX Complex (Human)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV use only

number of units indicated on label

Bebulin VH (with sterile water for injection diluent; heat-treated, vapor method; may contain natural latex components in packaging; available with transfer and filter needles)

Baxter

ProfilnineSD (with sterile water for injection diluent; solvent/detergent-inactivated; available with transfer needle and microaggregate filter)

Grifols

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions January 2, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

100. Baxter. Bebulin VH Factor IX complex, vapor heated prescribing information. Glendale, CA; 2003 Jan.

101. Anon. Update: acquired immunodeficiency syndrome (AIDS) in persons with hemophilia. MMWR Morb Mortal Wkly Rep. 1984; 33:589-91. [PubMed 6434934]

102. Evatt BL, Ramsey RB, Lawrence DN et al. The acquired immunodeficiency syndrome in patients with hemophilia. Ann Intern Med. 1984; 100:499-504. [PubMed 6230977]

103. Fauci AS, Macher AM, Longo DL et al. Acquired immunodeficiency syndrome: epidemiologic, clinical, immunologic, and therapeutic considerations. Ann Intern Med. 1984; 100:92-106. [PubMed 6318629]

104. Thompson AR. Factor IX concentrates for clinical use. Semin Thromb Hemost. 1993; 19:25-8. [PubMed 8456321]

105. Anon. Antibodies to retrovirus etiologically associated with acquired immunodeficiency syndrome (AIDS) in populations with increased incidences of the syndrome. MMWR Morb Mortal Wkly Rep. 1984; 33:377-9. [PubMed 6330518]

106. Ramsey RB, Palmer EL, McDougal JS et al. Antibody to lymphadenopathy-associated virus in haemophiliacs with and without AIDS. Lancet. 1984; 2:397-8. [PubMed 6147470]

108. Arya SK, Gallo RC, Hahn BH et al. Homology of genome of AIDS-associated virus with genomes of human T-cell leukemia virus. Science. 1984; 225:927-30. [PubMed 6089333]

111. Jason J, McDougal JS, Holman RC et al. Human T-lymphotropic retrovirus type III/lymphadenopathy-associated virus antibody: association with hemophiliacs’ immune status and blood component usage. JAMA. 1985; 253:3409-15. [PubMed 2987559]

121. Kreiss JK, Kitchen LW, Prince HE et al. Human T cell leukemia virus type III antibody, lymphadenopathy, and acquired immune deficiency syndrome in hemophiliac subjects: results of a prospective study. Am J Med. 1986; 80:345-50. [IDIS 213727] [PubMed 3006485]

122. Anon. Surveillance of hemophilia-associated acquired immunodeficiency syndrome. MMWR Morb Mortal Wkly Rep. 1986; 35:669-71. [PubMed 3095619]

123. Hardy AM, Allen JR, Morgan WM et al. The incidence rate of acquired immunodeficiency syndrome in selected populations. JAMA. 1985; 253:215-20. [PubMed 3965772]

125. Eyster ME, Gail MH, Ballard JO et al. Natural history of human immunodeficiency virus infections in hemophiliacs: effects of T-cell subsets, platelet counts, and age. Ann Intern Med. 1987; 107:1-6. [PubMed 3496028]

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