Medication Guide App

Factor IX Concentrates

Pronunciation: FAK-tor
Class: Antihemophilic agent Factor IX (human)

Trade Names

AlphaNine SD
- Injection, lyophilized powder for solution 500 units
- Injection, lyophilized powder for solution 1,000 units
- Injection, lyophilized powder for solution 1,500 units

Mononine
- Injection, lyophilized powder for solution 500 units
- Injection, lyophilized powder for solution 1,000 units

Factor IX (recombinant)

BeneFIX
- Injection, lyophilized powder for solution 250 units
- Injection, lyophilized powder for solution 500 units
- Injection, lyophilized powder for solution 1,000 units
- Injection, lyophilized powder for solution 2,000 units
- Injection, lyophilized powder for solution 3,000 units

Factors IX, II, X, and low amounts of VII (human)

Bebulin VH
- Injection, lyophilized powder for solution

Profilnine SD
- Injection, lyophilized powder for solution

Immunine VH (Canada)

Pharmacology

Restores hemostasis in patients with factor IX deficiency.

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Pharmacokinetics

Elimination

Mean biologic half-life is 18.1 to 25.3 h (adults) and approximately 19.8 to 21.1 h (children).

Indications and Usage

Control and prevention of hemorrhagic episodes in patients with factor IX deficiency (hemophilia B [Christmas disease]). BeneFIX is also indicated for perioperative management in adults and children with hemophilia B.

Contraindications

Life-threatening, immediate hypersensitivity reactions, including anaphylaxis, to the product; hypersensitivity to hamster protein ( BeneFIX ); hypersensitivity to mouse protein ( Mononine ).

Dosage and Administration

Factor IX Deficiency
Adults and Children

IV

AlphaNine SD

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

Minor hemorrhage (eg, bruises, cuts or scrapes, uncomplicated joint hemorrhage)

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

Moderate hemorrhages (eg, nosebleeds, mouth and gum bleeds, dental extractions, hematuria)

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

Major hemorrhage (eg, joint and muscle hemorrhage [especially in the large muscles], major trauma, hematuria, intracranial and intraperitoneal bleeding)

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

Surgery

Prior to surgery, factor IX should be brought to 50% to 100% of normal (50 to 100 units of factor IX/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% factor IX levels (50 to 100 units of factor IX/kg twice daily).

Bebulin VH

The method of calculating the Bebulin VH factor IX dose is as follows: Number of factor IX units required equals body weight (kg) × desired factor IX 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:

Minor hemorrhage (eg, early hemarthrosis, minor epistaxis and gingival bleeding, mild hematuria)

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

Moderate hemorrhage (eg, severe joint bleeding; early hematoma; major open bleeding; minor trauma; minor hemoptysis, hematemesis, and melena; major hematuria)

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

Major hemorrhage (eg, severe hematoma; major trauma; severe hemoptysis, hematemesis, and melena)

To achieve an approximate factor IX 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.

Major surgery

On the day of surgery, to achieve an approximate factor IX 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 factor IX 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 factor IX level of 20% of normal, administer 35 to 25 units/kg.

Minor surgery

On the day of surgery, to achieve an approximate factor IX 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 factor IX 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.

Long-term prophylaxis

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

BeneFIX

The method of calculating the BeneFIX dose is as follows:

  • Adults and children 15 y and older : Number of factor IX units required equals body weight (kg) × desired factor IX increase (percent or units/dL) × 1.3 units/kg (or units/dL).
  • Children younger than 15 y : Number of factor IX units required equals body weight (kg) × desired factor IX 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:

Minor hemorrhage (eg, uncomplicated hemarthrosis, superficial muscle, soft tissue)

For the required circulating factor IX 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.

Moderate hemorrhage (eg, intramuscular or soft tissue with dissection, mucous membranes, dental extractions, hematuria)

For the required circulating factor IX 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).

Major hemorrhage (eg, pharynx, retropharynx, retroperitoneum, CNS, surgery)

For the required circulating factor IX 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.

Mononine

The method of calculating the Mononine factor IX dose is as follows: Number of factor IX units required equals body weight (kg) × desired factor IX 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:

Minor spontaneous hemorrhage, prophylaxis

For desired levels of factor IX 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.

Major trauma or surgery

For desired levels of factor IX 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 factor IX levels. The duration of treatment is up to 10 days, depending on nature of insult.

Profilnine SD

The method of calculating the Profilnine SD factor IX dose is as follows: Number of factor IX units required equals body weight (kg) × desired increase in plasma factor IX (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.

Mild to moderate hemorrhage

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

Severe hemorrhage

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

Surgery

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

Dental extractions

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

General Advice

  • For IV administration only. Not for intradermal, subcutaneous, IM, or intra-arterial administration.
  • Refer to manufacturer's prescribing information for preparation for administration instructions.
  • 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 factor IX 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 2 mL/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.
  • BeneFIX should not be administered in the same tubing or container with other medicinal products.
  • Drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Storage/Stability

Store unreconstituted vials under refrigeration (35° to 46°F). Avoid freezing. BeneFIX may be stored at room temperature (not exceeding 86°F). 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. After reconstitution, products may be stored at room temperature and used within 3 h. Discard unused contents.

Drug Interactions

None well documented.

Adverse Reactions

Cardiovascular

Thromboembolic complications; hypotension (postmarketing).

CNS

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

Dermatologic

Rash (6%); hives (5%).

EENT

Blurred vision (2%).

GI

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

Genitourinary

Renal infarction (2%).

Hypersensitivity

Systemic hypersensitivity reactions, including bronchospastic reactions and/or hypotension and anaphylaxis; angioedema (postmarketing).

Local

Injection-site reaction (8%); injection-site pain (6%); cellulitis or phlebitis at IV site (2%).

Respiratory

Dyspnea (3%); dry cough, hypoxia (2%).

Miscellaneous

Factor IX inhibitor, fever, flushing (3%); chest tightness, chills (2%); elevated ALT; cyanosis, inadequate factor IX recovery, inadequate therapeutic response (postmarketing).

Precautions

Monitor

To ensure that desired factor IX activity level has been achieved, monitor factor IX activity using the factor IX activity assay. Monitor patients for the development of factor IX inhibitors. Closely monitor patients during infusion to observe for the development of any reaction.

Monitor for possible DIC and/or thrombosis in patients with liver disease, in patients with risk factors predisposing them to thrombosis, and in patients requiring high doses of factor IX because of major surgical interventions.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy of Profilnine SD have not been established in children 16 y and younger. Anecdotal evidence indicates no safety and efficacy differences between pediatric and adult populations treated with AlphaNine SD . BeneFIX has been evaluated for safety and efficacy in pediatric patients. A Mononine small trial showed safety and effectiveness in patients from 1 day to 20 years of age with excellent hemostasis without thrombotic complications.

Hypersensitivity

Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported. Evaluate patients experiencing allergic reactions for presence of factor IX inhibitor.

Hepatic Function

Use with caution.

Immune tolerance induction

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

Immunogenicity

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

Infusion reactions

May occur. Follow administration guidelines closely. If a reaction occurs, slow or stop infusion as dictated by patient response.

Thromboembolic complications

Because use of factor IX complex concentrates has been associated with development of thromboembolic complications, the use of factor IX–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, postoperative patients, neonates, or 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 (eg, viruses), and, theoretically, the Creutzfeldt-Jakob disease agent.

Overdosage

Symptoms

No symptoms have been reported.

Patient Information

  • Advise patients to contact their health care provider or treatment facility for further treatment and/or assessment if they experience a lack of a clinical response to factor IX replacement therapy; in some cases, this may be a manifestation of an inhibitor.
  • Advise patients to read the patient information leaflet before using the product the first time and with each refill.
  • Review benefits and risks of therapy, including the potential to transmit disease and unknown infectious agents.
  • Advise patients or caregivers that the 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, hypotension, rapid heartbeat, urticaria, wheezing). Instruct patients to contact their 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 their health care provider.

Copyright © 2009 Wolters Kluwer Health.

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