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Factor IX

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

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

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 deficiency100 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 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 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.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

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 HAV156 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

Interactions for Factor IX

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 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.

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; available with filter transfer set)

Grifols

Mononine (with sterile water for injection diluent; 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 (with sterile water for injection diluent; available with transfer and filter needles)

Baxter

Profilnine (with sterile water for injection diluent; available with filter transfer set)

Grifols

AHFS DI Essentials. © Copyright 2017, Selected Revisions January 25, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, 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 Factor IX complex, vapor heated prescribing information. Westlake Village, CA; 2012 July.

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. [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]

126. Centers for Disease Control. Human immunodeficiency virus infection in the United States. MMWR Morb Mortal Wkly Rep. 1987; 36:801-4. [PubMed 3119981]

127. Blomback M, Schulman S, Berntorp E et al. Survey of non-U.S. hemophilia treatment centers for HIV seroconversions following therapy with heat-treated factor concentrates. MMWR Morb Mortal Wkly Rep. 1987; 36:121-4. [PubMed 3102937]

128. White GC II, Matthews TJ, Weinhold KJ et al. HTLV-III seroconversion associated with heat-treated factor VIII concentrate. Lancet. 1986; 1:611-2. [PubMed 2869318]

129. van den Berg W, ten Cate JW, Breederveld C et al. Seroconversion to HTLV-III in haemophiliac given heat-treated factor VIII concentrate. Lancet. 1986; 1:803-4. [PubMed 2870298]

130. Anon. Armour withdrawl (sic: withdrawal) of 208 lots of H.T. Factorate. FDC Rep. 1987; 49(Dec 21):T&G-14.

131. Hemophilia Treatment Centers, National Hemophilia Foundation, Centers for Disease Control. HIV infection and pregnancies in sexual partners of HIV-seropositive hemophilic men—United States. MMWR Morb Mortal Wkly Rep. 1987; 36:593-5. [PubMed 3114605]

132. Prince AM. Effect of heat treatment of lyophilised blood derivatives on infectivity of human immunodeficiency. Lancet. 1986; 1:1280-1.

133. AIDS Group of the United Kingdom Haemophilia Centre Directors. Prevalence of antibody to HTLV-III in haemophiliacs in the United Kingdom. BMJ. 1986; 293:175-6.

135. Mariani G, Ghirardini A, Mandelli F et al. Heated clotting factors and seroconversion for human immunodeficiency virus in three hemophilic patients. Ann Intern Med. 1987; 107:113. [PubMed 3473956]

136. Allain JP, Laurian Y, Paul DA et al. Long-term evaluation of HIV antigen and antibodies to p24 and gp41 in patients with hemophilia: potential clinical importance. N Engl J Med. 1987; 317:1114-21. [PubMed 3477695]

137. Gomperts ED. Procedures for the inactivation of viruses in clotting factor concentrates. Am J Hematol. 1986; 23:295-305. [PubMed 3020979]

138. Rodell MB (Armour Pharmaceutical Company, Blue Bell, PA): Personal communication; 1988 Feb 1.

140. Grifols. Profilnine Factor IX complex solvent detergent treated prescribing information. Los Angeles, CA; 2013 Novr.

141. Anon. Safety of therapeutic products used for hemophilia patients. MMWR Morb Mortal Wkly Rep. 1988; 37:441-4,449-50. [PubMed 3134602]

142. Hyland. Proplex T Factor IX complex heat treated prescribing information. Glendale, CA; 1990 Nov.

143. National Hemophilia Foundation. CDC Reports West Nile Virus Transmission Modes. From National Hemophilia Foundation website.

145. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research (CBER). Guidance for industry. Revised preventive measures to reduce the possible risk of transmission of Creutzfeldt-Jacob disease (CJD) and variant Creutzfeldt-Jacob disease (vCJD) by blood and blood products. January 2002. From FDA website.

146. Ricketts MN, Cashman NR, Stratton EE et al. Is Creutzfeldt-Jacob disease transmitted in blood? Emerg Infectious Dis. 1997; 3:155-63.

147. Brown P, Will RG, Bradley R et al. Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease: background, evolution, and current concerns. Emerg Infectious Dis. 2001; 7:6-16.

148. Mannucci PM, Bauer KA, Gringeri A et al. Thrombin generation is not increased in the blood of hemophilia B patients after the infusion of a purified factor IX concentrate. Blood. 1990; 76:2540-5. [PubMed 2265248]

149. Herring S, Peddada L, Shitanishi K et al. Elimination of virus during manufacture of a coagulation factor IX concentrate. Paper presented at 19th International Congress World Federation of Hemophilia. Washington, DC: 1990 Aug 14-19.

151. Grifols. Alphanine SD Coagulation factor IX (human) solvent detergent treated/virus filtered prescribing information. Los Angeles, CA; 2013 Jan.

152. CSL Behring. Mononine Coagulation factor IX (human) monoclonal antibody purified prescribing information. Kankakee, IL; 2013 Feb.

153. Centers for Disease Control and Prevention. West Nile virus activity—United States, October 10–16, 2002, and update on West Nile virus infections in recipients of blood transfusions. MMWR Morb Mortal Wkly Rep. 2002; 51:929-31. [PubMed 12403410]

154. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research (CBER). Guidance for industry. Assessing donor suitability and blood and blood product safety in cases of known or suspected West Nile virus infection. Jun 2005. From FDA website ().

155. Medical and Scientific Advisory Council (MASAC), National Hemophilia Foundation. MASAC recommendation regarding the use of recombinant clotting factor products with respect to pathogen transmission (May 6, 2014). MASAC recommendation #226. From National Hemophilia Foundation website.

156. Medical and Scientific Advisory Council (MASAC), National Hemophilia Foundation. MASAC recommendations concerning products licensed for the treatment of hemophilia and other bleeding disorders (revised April 2014). MASAC recommendation #225. From National Hemophilia Foundation website.

157. Anon. Hepatitis A among persons with hemophilia who received clotting factor concentrate—United States, September-December 1995. MMWR Morb Mortal Wkly Rep. 1996; 45:29-32. [PubMed 8531917]

160. Medical and Scientific Advisory Council (MASAC), National Hemophilia Foundation. MASAC revised recommendations regarding hepatitis A and B immunization of individuals with bleeding disorders (November 2001). MASAC recommendation #128. From National Hemophilia Foundation website.

161. Naoumov NV, Petrova EP, Thomas MG et al. Presence of a newly described human DNA virus (TTV) in patients with liver disease. Lancet. 1998; 352:195-7. [PubMed 9683209]

162. Simmonds P, Davidson F, Lycett C et al. Detection of a novel DNA virus (TTV) in blood donors and blood products. Lancet. 1998; 352:191-5. [PubMed 9683208]

163. Harrington T, Kuehnert MF, Kamel H et al. West Nile virus infection transmitted by blood transfusion. Transfusion. 2003; 43:1018-22. [PubMed 12869105]

164. Iwamoto M, Jernigan DB, Gausch A et al. Transmission of West Nile virus from an organ donor to four transplant recipients. N Engl J Med. 2003; 348:2196-203. [PubMed 12773646]

165. Chiron. New test developed to screen donated blood for West Nile virus by July 1 deadline. Press release. 2003 June 18.

166. Centers for Disease Control and Prevention. Questions and answers: blood transfusions and organ donations. From the CDC website.

167. Hewitt PE, Llewelyn CA, Mackenzie J et al. Creutzfeldt-Jakob disease and blood transfusion: result of the UK transfusion medicine epidemiological review study. Vox Sang. 2006; 91:221-30. [PubMed 16958834]

170. Centers for Disease Control and Prevention (CDC). Hepatitis A fact sheet. 2007 Aug 9. From CDC website. Accessed 2007 Nov 13.

171. World Federation of Hemophilia. Guidelines for the management of hemophilia 2nd edition. 2012. From the World Federation of Hemophilia website.

172. Mannucci PM, Tuddenham EGD. The hemophilias—from royal genes to gene therapy. N Engl J Med. 2001; 344:1773-9. [PubMed 11396445]

173. Björkman S, Berntorp E. Pharmacokinetics of coagulation factor, clinical relevance for patients with haemophilia. Clin Pharmacokinet. 2001; 40:815-32.

174. Shord SS, Lindley CM. Coagulation products and their uses. Am J Health Syst Pharm. 2000; 57:1403-17. [PubMed 10938981]

175. Köhler M, Helistern P, Lechler E et al. Thromboembolic complications associated with the use of prothrombin complex and factor IX concentrates. Thromb Haemost. 1998; 80:399-402.

176. Medical and Scientific Advisory Council (MASAC), National Hemophilia Foundation. MASAC recommendation concerning prophylaxis (regular administration of clotting factor concentrate to prevent bleeding) (November 4, 2007). MASAC recommendation #179. From National Hemophilia Foundation website.

177. Baxter, Glendale, CA: Personal communication.

178. Bolton-Maggs PHB, Pasi KJ. Haemophilias A and B. Lancet. 2003; 361:1801-9.

179. Warrier I. Management of haemophilia B patients with inhibitors and anaphylaxis. Haemophilia. 1998; 4:574-6. [PubMed 9873797]

180. Giangrande P. Haemophilia B: Christmas disease. Expert Opin Pharmacother. 2005; 6:1517-24. [PubMed 16086639]

181. DiMichele D. Inhibitor development in haemophilia B: an orphan disease in need of attention. Br J Haematol. 2007; 138:305-15. [PubMed 17614818]

182. Roth DA, Kessler CM, Pasi KJ et al. Human recombinant factor IX: safety and efficacy studies in hemophilia B patients previously treated with plasma-derived factor IX concentrates. Blood. 2001; 98:3600-06. [PubMed 11739163]

183. Grifols, Los Angeles, CA: Personal communication.

184. Wyeth. BeneFIX coagulation factor IX (recombinant) prescribing information. Philadelphia, PA; 2007 Sep.

185. Carcao MD, Aledort L. Prophylactic factor replacement in hemophilia. Blood Rev. 2004; 18:101-13. [PubMed 15010149]

186. Nilsson IM, Berntorp E, Löfqvist T et al. Twenty-five years’ experience of prophylactic treatment in severe haemophilia A and B. J Intern med. 1992; 232:25-32. [PubMed 1640190]

187. Medical and Scientific Advisory Council (MASAC), National Hemophilia Foundation. MASAC recommendations regarding factor concentrate prescriptions and formulary development and restrictions (March 12, 2005). MASAC recommendation #159. From National Hemophilia Foundation website ().

188. The United States pharmacopeia, 32nd rev, and The national formulary, 22nd ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 2009: 2342.

191. Biogen Idec. Alprolix coagulation factor IX (recombinant), Fc fusion protein prescribing information. Cambridge, MA; 2014 Mar.

192. CSL Behring LLC. Kcentra Prothrombin complex concentration (human) prescribing information. Kankakee, IL; 2014 March.

193. Morgenstern LB, Hemphill JC, Anderson C et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2010; 41:2108-29. [PubMed 20651276]

194. Kalus JS. Pharmacologic interventions for reversing the effects of oral anticoagulants. Am J Health Syst Pharm. 2013; 70(10 Suppl 1):S12-21.

195. Ageno W, Gallus AS, Wittkowsky A et al. Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e44S-88S. [PubMed 22315269]

196. Dentali F, Marchesi C, Pierfranceschi MG et al. Safety of prothrombin complex concentrates for rapid anticoagulation reversal of vitamin K antagonists. A meta-analysis. Thromb Haemost. 2011; 106:429-38. [PubMed 21800002]

197. Frumkin K. Rapid reversal of warfarin-associated hemorrhage in the emergency department by prothrombin complex concentrates. Ann Emerg Med. 2013; 62:616-626.e8. [PubMed 23829955]

199. Dager WE. Using prothrombin complex concentrates to rapidly reverse oral anticoagulant effects. Ann Pharmacother. 2011; 45:1016-20. [PubMed 21775688]

a. AHFS Drug Information 2016. McEvoy GK, ed. Factor IX (human), factor IX complex (human). Bethesda, MD: American Society of Health-System Pharmacists; 2016.

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