Antihemophilic Factor (Recombinant [Fc Fusion Protein])

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous [preservative free]:

Eloctate: 250 units (1 ea); 500 units (1 ea); 750 units (1 ea); 1000 units (1 ea); 1500 units (1 ea); 2000 units (1 ea); 3000 units (1 ea); 4000 units (1 ea); 5000 units (1 ea); 6000 units (1 ea)

Pharmacology

Mechanism of Action

Factor VIII replacement, necessary for clot formation and maintenance of hemostasis. It activates factor X in conjunction with activated factor IX; activated factor X converts prothrombin to thrombin, which converts fibrinogen to fibrin, and with factor XIII forms a stable clot.

Pharmacokinetics/Pharmacodynamics

Distribution

V_ss: Children <12 years: ~0.52 to 0.59 dL/kg; Children ≥12 years, Adolescents, and Adults: ~0.50 to 0.6 dL/kg

Half-Life Elimination

Children <12 years: 12.7 to 14.9 hours; Children ≥12 years, Adolescents, and Adults: 16.4 to 19.7 hours

Use in Specific Populations

Special Populations: Children

Compared to adults, children have a shorter half-life and lower recovery of factor VIII; clearance (based on per kg body weight) is higher in pediatric patients.

Use: Labeled Indications

Hemophilia A:

Control and prevention of bleeding episodes: For the prevention and control of bleeding episodes in adults and children with hemophilia A.

Perioperative management: For surgical prophylaxis in adults and children with hemophilia A.

Routine prophylaxis to prevent or reduce the frequency of bleeding: For routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes in adults and children with hemophilia A.

Limitation of use: Not indicated for the treatment of von Willebrand disease.

Contraindications

Life-threatening hypersensitivity to antihemophilic factor or any component of the formulation.

Dosage and Administration

Dosing: Adult

Hemophilia A: IV: Individualize dosage based on coagulation studies performed prior to treatment and at regular intervals during treatment. In general, administration of factor VIII 1 unit/kg will increase circulating factor VIII levels by ~2 units/dL.

Control and prevention of bleeding episodes or perioperative management:

Dosage based on desired factor VIII increase (%) (WFH [Srivastava 2013]):

To calculate dosage needed based on desired factor VIII increase (%):

[Body weight (kg) x desired factor VIII increase (%)] divided by 2 (%/units/kg) = units factor VIII required

For example:

50 kg x 30 (% increase) divided by 2 = 750 units factor VIII

Dosage based on expected factor VIII increase (%) (WFH [Srivastava 2013]):

It is also possible to calculate the expected % factor VIII increase:

[# units administered x 2 (%/units/kg)] divided by body weight (kg) = expected % factor VIII increase

For example:

[1,400 units x 2] divided by 70 kg = 40%

World Federation of Hemophilia (WFH) treatment recommendations when no significant resource constraint exists (WFH [Srivastava 2013]):

World Federation of Hemophilia (WFH) treatment recommendations when no significant resource constraint exists (Srivastava 2013):

Desired Factor VIII Level to Maintain and Duration Based on Site of Hemorrhage/Clinical Situation:

Joint: 40 to 60 units/dL for 1 to 2 days, may be longer if response is inadequate

Superficial muscle (no neurovascular compromise): 40 to 60 units/dL for 2 to 3 days, sometimes longer if response is inadequate

Iliopsoas and deep muscle with neurovascular injury, or substantial blood loss: Initial: 80 to 100 units/dL for 1 to 2 days; Maintenance: 30 to 60 units/dL for 3 to 5 days, sometimes longer as secondary prophylaxis during physiotherapy

CNS/head: Initial: 80 to 100 units/dL for 1 to 7 days; Maintenance: 50 units/dL for 8 to 21 days

Throat and neck: Initial: 80 to 100 units/dL for 1 to 7 days; Maintenance: 50 units/dL for 8 to 14 days

Gastrointestinal: Initial: 80 to 100 units/dL for 7 to 14 days; Maintenance: 50 units/dL (duration not specified)

Renal: 50 units/dL for 3 to 5 days

Deep laceration: 50 units/dL for 5 to 7 days

Surgery (major): Preop: 80 to 100 units/dL; Postop: 60 to 80 units/dL for 1 to 3 days; then 40 to 60 units/dL for 4 to 6 days; then 30 to 50 units/dL for 7 to 14 days

Surgery (minor): Preop: 50 to 80 units/dL; Postop: 30 to 80 units/dL for 1 to 5 days depending on procedure type

Note: Factor VIII level may either be expressed as units/dL or as %. Dosing frequency most commonly corresponds to the half-life of factor VIII but should be determined based on an assessment of factor VIII levels before the next dose.

Manufacturer's labeling: Dosing in the prescribing information may not reflect current clinical practice. Refer to manufacturer's labeling for specific recommendations.

Routine prophylaxis to prevent or reduce the frequency of bleeding episodes: IV: 50 units/kg every 4 days; at 3- to 5-day intervals, may adjust dose within the range of 25 to 65 units/kg based on patient response. Maintain trough levels between 1% and 3% above baseline, or higher, as clinically indicated.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Hemophilia A: Children and Adolescents: IV: Individualize dosage based on coagulation studies performed prior to treatment and at regular intervals during treatment. In general, administration of factor VIII 1 unit/kg will increase circulating factor VIII levels by ~2 units/dL. Children <6 years may require higher doses and/or more frequent administration.

Control and prevention of bleeding episodes or perioperative management: Refer to adult dosing.

Routine prophylaxis to prevent bleeding episodes:

Children <6 years: 50 units/kg twice weekly; at 3- to 5-day intervals, may adjust dose within the range of 25 to 65 units/kg based on patient response. More frequent or higher doses (up to 80 units/kg) may be required.

Children ≥6 years and Adolescents: Refer to adult dosing.

Reconstitution

If refrigerated, the dried concentrate and diluent should be warmed to room temperature before reconstitution. Gently agitate or rotate vial after adding diluent, do not shake vigorously. Refer to product specific labeling for reconstitution instructions and for detailed information regarding compatibility with administration sets.

Administration

IV: Infuse at a rate of ≤10 mL/minute (maximum: 10 mL/minute)

According to the World Federation of Hemophilia (WFH), infuse by slow IV injection at a rate not to exceed 3 mL/minute (WFH [Srivastava 2013]).

Storage

Prior to reconstitution, store refrigerated at 2°C to 8°C (36°F to 46°F); do not freeze. May also store at room temperature (not to exceed 30°C [86°F]) up to 6 months; do not return to refrigerator. Store in original package to protect from light. Use within 3 hours of reconstitution; do not refrigerate after reconstitution.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

<1%, postmarketing, and/or case reports: Antibody development (neutralizing), arthralgia, back pain, bradycardia, chest pain, cough, dizziness, dysgeusia, feeling hot, headache, hot flash, hypersensitivity reaction, hypertension, joint swelling, lower abdominal pain, malaise, myalgia, procedural hypotension, sensation of cold, skin rash, venous pain (postinjection)

Warnings/Precautions

Concerns related to adverse effects:

• Antibody formation: The development of factor VIII antibodies has been reported with antihemophilic factors; monitor for signs of formation of antibodies to factor VIII; may occur at any time but more common in young children with severe hemophilia. Suspect factor VIII antibodies if the plasma factor VIII level does not increase as expected or if bleeding is not controlled after administration.
• Hypersensitivity reactions: Allergic hypersensitivity reactions (including anaphylaxis) may occur; discontinue if hypersensitivity symptoms occur and administer appropriate treatment.

Dosage form specific issues:

• Sucrose: May contain sucrose.

Other warnings/precautions:

• Dose requirements: The dosage requirement will vary in patients with factor VIII inhibitors; optimal treatment should be determined by clinical response.

Monitoring Parameters

Heart rate and blood pressure (before and during IV administration); plasma factor VIII activity prior to and during treatment; development of factor VIII inhibitors; signs of bleeding; hemoglobin, hematocrit; hypersensitivity reactions

Pregnancy

Pregnancy Considerations

Pregnant hemophilia A carriers may have an increased bleeding risk following abortion, invasive procedures, miscarriage, and delivery; close surveillance is recommended. Factor VIII levels should be monitored at the first antenatal visit, once or twice during the third trimester, prior to surgical or invasive procedures, and at delivery. Although factor VIII concentrations increase in pregnant patients, factor VIII replacement is recommended if concentrations are <0.5 IU/mL and any of the following occur: need for invasive procedures (including delivery), spontaneous miscarriage, insertion and removal of epidural catheters, or active bleeding. Hemostatic factor VIII concentrations should be maintained for at least 3 to 5 days following invasive procedures or postpartum. If a replacement product is indicated, a recombinant product is preferred (NHF 2017; RCOG [Pavord 2017]; WFH [Srivastava 2013]).

Patient Education

What is this drug used for?

• It is used to treat hemophilia.
• It is used to treat or prevent bleeding.

Frequently reported side effects of this drug

• Headache
• Loss of strength and energy
• Injection site irritation
• Muscle pain
• Joint pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.