Brand names: AlphaNine SD, Bebulin, Mononine, Profilnine
Drug class: Hemostatics
VA class: BL500
CAS number: 37224-63-8

Medically reviewed by Drugs.com on Jan 15, 2025. Written by ASHP.

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 hemophilia B (congenital factor IX deficiency or 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, some experts state that pure (i.e., single-factor) factor IX preparations are preferred over factor IX complex for treatment of hemophilia B.^{148 152 171 174} (See Thromboembolic Events under Cautions.)

Also used for routine prophylaxis (i.e., administration at regular intervals on an ongoing basis) to prevent or reduce frequency of hemorrhagic events.^{171 173 176 178 180 185 186} Such prophylactic therapy currently considered the standard of care for patients with hemophilia B.^{171 176} Decreases frequency of spontaneous musculoskeletal hemorrhage, preserves joint function, and improves quality of life.^{171 176 185 186}

Several factor IX concentrates are currently available in the US, including a variety of recombinant and plasma-derived preparations;¹⁵⁶ the Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Foundation recommends preferential use of recombinant factor IX preparations because of their potentially superior safety profile with respect to pathogen transmission.^{155 156 176} (See Risk of Transmissible Agents in Plasma-derived Preparations under Cautions.) Other experts (e.g., World Federation of Hemophilia) state that choice of preparation should be determined by local criteria.¹⁷¹ When selecting an appropriate factor IX preparation, consider characteristics of each clotting factor concentrate, individual patient variables, patient/provider preference, and emerging data.^{155 156 171 187}

Factor IX (human) is not indicated for treatment of coagulation factor II, VII, or X deficiency or for management of hemophilia A in patients with inhibitors to factor VIII.^{151 152}

Factor IX complex (human) is not indicated for treatment of factor VII deficiency^{100 140} or other coagulation factor deficiencies.¹⁰⁰

Reversal of Warfarin Anticoagulation

Factor IX complex (human) (i.e., 3-factor PCC) has been used for urgent reversal of warfarin anticoagulation^{† [off-label]} in patients experiencing major bleeding or in those who require immediate reversal of anticoagulation for other reasons (e.g., urgent surgery).^{100 140 193 194 195 196 197}

Factor IX (human) is not indicated for treatment or reversal of coumarin-induced anticoagulation or for treatment of 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

• 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.)

• Monitor factor IX levels frequently to individualize dosage and assess response to therapy.^{100 140 151 152} Close monitoring of factor IX levels is particularly important in cases of severe hemorrhage or major surgery.¹⁰⁰ (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^{† [off-label]}.^{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: Administer at a rate ≤2 mL/minute.¹⁰⁰

Profilnine: 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}

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

Estimate dosage of AlphaNine SD, Mononine, or Profilnine using the following formula:^{140 151 152}

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

Estimate dosage of Bebulin using the following formula:¹⁰⁰

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

The desired factor IX level is determined by the clinical situation and severity of hemorrhage.^{151 152} For recommendations on target factor IX levels, see the individual product-specific dosage sections below. 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.^{100 140 151 152 a}

If calculated dose 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 doses may be required in such situations;¹⁵² however, caution is advised when administering higher than recommended doses.¹⁵¹ (See Thromboembolic Events under Cautions.)

Pediatric Patients

Hemophilia B

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

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} Individualize prophylactic regimens; evaluate patients periodically to determine continued need for prophylaxis.¹⁷⁶

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

Bebulin (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, 50–65 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, 75–90 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 50–75 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 25–65 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, 75–90 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 25–75 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 (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} Individualize prophylactic regimens; evaluate patients periodically to determine continued need for prophylaxis.¹⁷⁶

Prescribing Limits

Adults

Hemophilia B

IV

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

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

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

Contraindications

• Mononine: Known hypersensitivity to murine protein.¹⁵²

• Bebulin: Known hypersensitivity to factor IX complex (human), hypersensitivity to heparin, or history of heparin-induced thrombocytopenia (HIT).¹⁰⁰

• The manufacturers state that there are no known contraindications to the use of AlphaNine SD or Profilnine.^{140 151}

Warnings/Precautions

Warnings

Risk of Transmissible Agents in Plasma-derived Preparations

Possibility exists for transmission of human viruses (e.g., HIV, hepatitis A virus [HAV], hepatitis B virus [HBV], hepatitis C virus [HCV]) and other infectious agents (e.g., unknown viruses; causative agents for Creutzfeldt-Jakob disease [CJD] or variant CJD [vCJD]).^{100 130 140 145 146 147 151 152 155 156 161 162}

Improved donor screening and viral-inactivating/eliminating procedures (e.g., solvent/detergent, heat-treatment, chromatography, nanofiltration) have reduced but not completely eliminated risk of pathogen transmission with plasma-derived factor IX and factor IX complex preparations.^{100 130 140 152 155 156 180}

Although transmission of nonenveloped viruses, including HAV^{156 157} and parvovirus B19,¹⁵⁶ has been documented following administration of plasma-derived coagulation factors, risk has been reduced with additional viral attenuation methods such as nanofiltration.^{100 140 151 152 156 172 182} Nevertheless, 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.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.^{100 140 174 175} 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 concentrates; 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 (i.e., single-factor) 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 If evidence of thrombosis or DIC occurs during therapy, discontinue drug immediately and administer appropriate treatment.¹⁰⁰

Nephrotic Syndrome

Nephrotic syndrome reported following immune tolerance induction with factor IX-containing products in patients with hemophilia B who have inhibitors and/or a history of hypersensitivity reactions to factor IX.^{100 151 152 172 178 179 180}

Safety and efficacy of factor IX products for immune tolerance induction not established.^{100 151 152}

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (hives, pruritus, edema, chest tightness, angioedema, dyspnea, wheezing, faintness, hypotension, tachycardia, generalized urticaria, shock) reported with use of all factor IX products.^{100 140 151 152 172}

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

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}

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.)

General Precautions

Development of Inhibitors to Factor IX

Risk for development of neutralizing antibodies (inhibitors) 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.)

Because of an association between inhibitor development and allergic reactions, evaluate for presence of inhibitors in any patient experiencing hypersensitivity.¹⁰⁰

Monitor patients regularly for development of inhibitors.^{151 152 171} (See Laboratory Monitoring under Cautions.) Suspect presence of inhibitors if expected factor IX levels not achieved or bleeding not controlled with recommended dose, particularly in those who previously achieved a response.¹⁷¹

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

Laboratory Monitoring

Monitor factor IX levels at regular intervals 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 patients 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: Safety and efficacy not established.^{100 177}

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 generally based on the same guidelines as for adults.¹⁵²

Profilnine: Safety and efficacy not established in patients ≤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

Drug Interactions

Specific Drugs

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: 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: ≤25°C; do not freeze.¹⁴⁰ Use solution within 3 hours of reconstitution.¹⁴⁰

Actions

• Factor IX (human) and factor IX complex (human) preparations are purified concentrates of factor IX derived from human plasma.^{100 140 151 152} Factor IX complex (human) preparations also contain variable amounts of vitamin K-dependent clotting factors II, VII, and X.^{100 140 173 174}

• 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 exogenous factor IX to patients with hemophilia B results in increased plasma levels of factor IX and temporarily corrects coagulation defects.¹⁵²

• Factor IX (human) and factor IX complex (human) are prepared from pooled human plasma; different methods (e.g., murine monoclonal antibody, chromatography, nanofiltration) 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 human plasma-derived factor concentrates.^{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} Parvovirus B19 infection is especially serious in pregnant or immunocompromised patients.¹⁰⁰

• 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.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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