Factor IX Concentrates

Trade Names:AlphaNine SD- Injection, lyophilized powder for solution of dried plasma fraction of factor IX (human)

Trade Names:Bebulin VH- Injection, lyophilized powder for solution of purified freeze-dried concentrate of coagulation factors IX, II, X, and low amounts of VII (human), heat-treated

Trade Names:BeneFIX- Injection, lyophilized powder for solution of factor IX, recombinant

Trade Names:Mononine- Powder Injection, lyophilized powder for solution of factor IX (human), plasma-derived

Trade Names:Profilnine SD- Injection, lyophilized powder for solution of factors IX, II, X, and low amount of VII (human), plasma-derived

Pharmacology

Restores hemostasis in patients with factor IX (FIX) deficiency.

Pharmacokinetics

Elimination

Mean biologic half-life is 18.8 to 25.3 h (adults) and approximately 20.2 h (children).

Indications and Usage

Control and prevention of hemorrhagic episodes in patients with FIX deficiency (hemophilia B, Christmas disease).

Perioperative management in adults and children with hemophilia B.

Contraindications

None known.

Hypersensitivity to hamster protein.

Hypersensitivity to mouse protein.

Dosage and Administration

IV

The method of calculating the AlphaNine SD FIX dose is as follows: Number of FIX units required equals body weight (kg) × desired increase in plasma FIX (percent of normal) × 1 unit/kg. The following are treatment guidelines using AlphaNine SD for hemorrhagic events and surgery in patients diagnosed with hemophilia B:

FIX levels should be brought to at least 20% to 30% (20 to 30 units of FIX/kg twice daily) until hemorrhage stops and healing has been achieved (1 to 2 days).

FIX levels should be brought to 25% to 50% (25 to 50 units of FIX/kg twice daily) until healing has been achieved (2 to 7 days, or average).

FIX levels should be brought to 50% for at least 3 to 5 days (30 to 50 units of FIX/kg twice daily). Following this treatment period, FIX levels should be maintained at 20% (20 units of FIX/kg twice daily) until healing has been achieved. Major hemorrhages may require treatment for up to 10 days.

Prior to surgery, FIX should be brought to 50% to 100% of normal (50 to 100 units of FIX/kg twice daily). For the next 7 to 10 days, or until healing has been achieved, the patient should be maintained at 50% to 100% FIX levels (50 to 100 units of FIX/kg twice daily).

The method of calculating the Bebulin VH FIX dose is as follows: Number of FIX units required equals body weight (kg) × desired FIX increase (percent of normal) × 1.2. The following are treatment guidelines using Bebulin VH for hemorrhagic events and surgery in patients diagnosed with hemophilia B:

To achieve an approximate FIX level of 20% of normal, the typical initial dose is 25 to 35 units/kg for 1 day.

To achieve an approximate FIX level of 40% of normal, the typical initial dose is 40 to 55 units/kg for 2 days or until adequate wound healing.

To achieve an approximate FIX level of at least 60% of normal, the typical initial dose is 60 to 70 units/kg for 2 to 3 days or until adequate wound healing.

On the day of surgery, to achieve an approximate FIX level of at least 60% of normal, administer 70 to 95 units/kg. During the initial postoperative period (first and second week), to achieve an approximate FIX level of 60% to 20% of normal, administer 70 to 35 units/kg. During the late postoperative period (from third week onwards), to achieve an approximate FIX level of 20% of normal, administer 35 to 25 units/kg.

On the day of surgery, to achieve an approximate FIX level of 40% to 60% of normal, administer 50 to 60 units/kg. During the initial postoperative period (first and second week), to achieve an approximate FIX level of 40% to 20% of normal, administer 55 to 25 units/kg. Dosing guidelines for the late postoperative period (from third week onwards) are not applicable.

20 to 30 units/kg administered once, or preferably up to twice weekly, have been shown to reduce frequency of spontaneous hemorrhage. However, prophylactic dosage regimens should be tailored to individual needs.

The method of calculating the BeneFIX dose is as follows:

• Adults : Number of FIX units required for adults equals body weight (kg) × desired FIX increase (percent or units/dL) × 1.3 units/kg (or units/dL).
• Children younger than 15 yr of age : Number of FIX units required equals body weight (kg) × desired FIX increase (percent or units/dL) × 1.4 units/kg (or units/dL).

The following are treatment guidelines using BeneFIX for hemorrhagic events and surgery in patients diagnosed with hemophilia B:

For the required circulating FIX activity of 20% to 30% (or units/dL), the dosing interval should be 12 to 24 h for a duration of 1 to 2 days.

For the required circulating FIX activity of 25% to 50% (or units/dL), the dosing interval should be 12 to 24 h administered until bleeding stops and healing begins (about 2 to 7 days).

For the required circulating FIX activity of 50% to 100% (or units/dL), the dosing interval should be 12 to 24 h for a duration of 7 to 10 days.

The method of calculating the Mononine FIX dose is as follows: Number of FIX units required equals body weight (kg) × desired FIX increase (percent or units/dL) × 1 unit/kg (or units/dL). The following are treatment guidelines using Mononine for hemorrhagic events and surgery in patients diagnosed with hemophilia B:

For desired levels of FIX for hemostasis of 15% to 25% (or units/dL), administer an initial loading dose of up to 20 to 30 units/kg, which may be repeated once in 24 h if needed. The duration of treatment is once and may be repeated if needed.

For desired levels of FIX for hemostasis of 25% to 50% (or units/dL), administer an initial loading dose of up to 75 units/kg, which may be repeated every 18 to 30 h depending on half-life and measured FIX levels. The duration of treatment is up to 10 days, depending upon nature of insult.

The method of calculating the Profilnine SD FIX dose is as follows: Number of FIX units required equals body weight (kg) × desired increase in plasma FIX (percent of normal) × 1 unit/kg. The following are treatment guidelines using Profilnine SD for hemorrhagic events and surgery in patients diagnosed with hemophilia B.

May usually be treated with a single administration sufficient to raise plasma FIX level to 20% to 30%.

Raise plasma FIX to 30% to 50%. Infusions are generally required daily.

FIX level should be raised to 30% to 50% for at least 1 week following surgery.

FIX level should be raised to 50% immediately prior to the procedure. Administer additional FIX complex if bleeding occurs.

General Advice

• For IV administration only. Not for intradermal, subcutaneous, IM, or intra-arterial administration.
• Administer reconstituted solution within 3 h of reconstitution. Reconstituted solution may be stored at room temperature prior to administration. Do not refrigerate reconstituted solution. Do not freeze.
• Administer reconstituted solution through infusion set tubing. Limit the amount of blood entering tubing. If red blood cell agglutination is observed in the tubing or syringe, discard all material (tubing, syringe, and FIX solution) and resume administration with a new package.
• Rates of infusion vary with product: Profilnine SD rate, less than 10 mL/min; Mononine , up to 225 units/min; Bebulin VH , no more than 2 mL/min; AlphaNine SD , less than 10 mL/min; BeneFIX , over several min. Rate of administration is determined by patient's comfort level.
• If headache, flushing, or changes in heart rate or BP appear, stop the infusion until symptoms subside, then resume at a slower rate.

Storage/Stability

BeneFIX may be stored at room temperature (not exceeding 77°F) for up to 6 mo. Profilnine SD may be stored at room temperature (not exceeding 86°F) for up to 3 mo. Mononine may be stored at room temperature (not exceeding 77°F) for up to 1 mo. AlphaNine SD may be stored at room temperature (not exceeding 86°F) for up to 1 mo. Store Bebulin VH at 35° to 46°F; avoid freezing.

Drug Interactions

May increase risk of thrombosis.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Deep vein thrombosis, hypotension, superior vena cava syndrome, thrombophlebitis, thrombosis (postmarketing).

CNS

Headache (11%); dizziness (8%); somnolence (3%); drowsiness, shaking (2%); lethargy.

Dermatologic

Rash (8%); hives (5%); urticaria.

EENT

Allergic rhinitis (5%); blurred vision, visual disturbances (2%).

GI

Nausea (6%); taste perversion (5%); diarrhea, vomiting (2%).

Genitourinary

Renal infarct (2%).

Hypersensitivity

Anaphylaxis, angioedema, laryngeal edema (postmarketing).

Lab Tests

Elevated ALT or AST, increased alkaline phosphatase (2%).

Local

Injection-site pain (6%); cellulitis or phlebitis at IV site, injection-site reaction (2%).

Respiratory

Dyspnea (3%); dry cough, lung disorder (2%).

Miscellaneous

FIX inhibitor, fever, flushing, shaking (3%); allergic reaction, asthma, burning sensation in jaw and skull, chest tightness, chills, hepatitis A virus seroconversion, hypoxia, parvovirus B19 seroconversion, photosensitivity (2%); tingling; cyanosis, inadequate FIX recovery, inadequate therapeutic response, inhibitor development (postmarketing).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy of Profilnine SD and AlphaNine SD have not been established in children 16 yr of age and younger. A Mononine small trial showed safety and effectiveness in patients from 1 day to 20 years of age with excellent hemostasis without thrombotic complications.

Elderly

Studies did not include sufficient numbers of patients 65 yr of age and older to determine if they respond differently from younger patients. Dose selection should be individualized.

Hypersensitivity

Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported. Evaluate patient experiencing allergic reaction for presence of FIX inhibitor.

Immune tolerance induction

Nephrotic syndrome has been reported following immune tolerance induction with FIX concentrates in hemophilia B patients with FIX inhibitors and a history of allergic reactions to FIX. Safety and efficacy of using BeneFIX for immune tolerance induction have not been established.

Latex sensitivity

Diluent vial for BeneFIX packaging may contain dry natural latex rubber that may cause allergic reactions in latex-sensitive individuals.

Neutralizing antibodies

If expected plasma factor IV activity levels are not attained, or if bleeding is not controlled with the expected dose, an assay to measure FIX inhibitor concentration should be performed. Patients with FIX inhibitors may be at increased risk of anaphylaxis upon subsequent challenge with FIX.

Thromboembolic complications

Because use of FIX complex concentrates has been associated with development of thromboembolic complications, the use of FIX-containing products may be potentially hazardous in patients with signs of fibrinolysis or with DIC. Use with caution when administering to patients with liver disease, patients postoperatively, neonates, or to patients at risk of thromboembolic phenomena or DIC.

Viral infections (eg, hepatitis)

All products except BeneFIX are prepared from pooled units of human plasma and may carry a risk of transmitting infectious agents.

Overdosage

Symptoms

No symptoms have been reported.

Patient Information

• Advise patient to read the patient information leaflet before using product the first time and with each refill.
• Review benefits of therapy and risks, including potential to transmit disease and unknown infectious agents.
• Advise patient or caregiver that medication will be prepared and administered by a health care provider in a health care setting.
• Review signs and symptoms of hypersensitivity reactions (eg, angioedema, chest tightness, difficulty breathing or unexplained shortness of breath, faintness, hives, rapid heartbeat, wheezing). Instruct patient to contact health care provider and/or seek immediate emergency care depending on the severity of the reaction.
• Advise patients to report dark urine, symptoms of poor appetite, tiredness, yellowed complexion, or low-grade fever followed by nausea, vomiting, and stomach pain to health care provider.

Copyright © 2009 Wolters Kluwer Health.