Antihemophilic Factor (Recombinant)

Class: Hemostatics
VA Class: BL500
CAS Number: 9001-27-8
Brands: Advate, Helixate FS, Kogenate FS, Recombinate, ReFacto

Introduction

Biosynthetic preparation (recombinant DNA origin) of antihemophilic factor (blood coagulation factor VIII).^{1 2 7 8 10 11 40 120 121 122} Structurally similar to endogenous human factor VIII and produces the same biologic effects as plasma-derived antihemophilic factor (human).^{1 2 3 4 7 8 9 10 40 49 50 69 77 120 121 122}

Uses for Antihemophilic Factor (Recombinant)

Hemophilia A

Prevention and control of hemorrhagic episodes in patients with a deficiency of coagulation factor VIII (antihemophilic factor) associated with hemophilia A (classic hemophilia);^{1 2 3 4 5 9 23 24 40 41 47 48 55 56 68 69 73 74 76 79 114 120 121 122 126} designated an orphan drug by FDA for this use.¹¹⁴

Because of a decreased risk of transmission of human viruses (e.g., HIV viruses, hepatitis A virus [HAV], hepatitis B virus [HBV], hepatitis C virus [HCV]) and other transmissible disease agents (e.g., agents for Creutzfeldt-Jakob disease [CJD], variant CJD [vCJD]) compared with plasma-derived antihemophilic factor (human), the Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Foundation and other experts recommend antihemophilic factor (recombinant) as the preferred preparation when antihemophilic factor therapy is indicated in patients with hemophilia A.^{3 4 8 9 14 40 49 52 55 69 73 76 79 110} Recombinant and plasma-derived preparations of antihemophilic factor produce comparable hemostatic effects.^{3 8 9 14 40 47 48 49 69 73 76}

Antihemophilic factor generally is used in patients with mild to moderate hemophilia A who do not respond adequately to desmopressin or those with moderate to severe hemophilia A and factor VIII level <5% of normal.^{56 68 74 79 95 96 126}

Maintenance of hemostasis in patients with hemophilia A undergoing minor surgery (e.g., tooth extraction, elective circumcision) or major surgery (e.g., bilateral osteotomies, thoracotomy, liver transplant, joint replacement, laparotomy, prostatectomy, lumbar puncture, bilateral inguinal herniorrhaphy).^{1 2 76 120 121 122}

Effective in the management of spontaneous or traumatic bleeding episodes (e.g., hemarthrosis, IM hematoma, soft tissue hemorrhage) or acute bleeding events (e.g., GI, retroperitoneal, tonsillar, ocular) in patients with hemophilia A.^{1 3 5 47 48 76}

Also used for routine prophylaxis (i.e., administration at regular intervals) to prevent or reduce frequency of hemorrhagic events and preserve joint function.^{2 121 126 d e h i l} MASAC and the World Federation of Hemophilia recommend prophylaxis for patients with severe hemophilia A (factor VIII activity <1%) after careful consideration of risks versus benefits.^{129 l}

Not indicated for treatment of von Willebrand disease.^{1 2 119 120 121 122}

Hemophilia A with Inhibitors to Antihemophilic Factor

Prevention and treatment of bleeding in patients with hemophilia A who have developed relatively low levels of inhibitor antibodies to factor VIII.^{1 2 27 55 85 120 121 122 126} (See Development of Inhibitors to Antihemophilic Factor under Cautions.) Some manufacturers state that antihemophilic factor may be effective in patients with inhibitor levels ≤10 Bethesda units/mL;^{1 122} other clinicians recommend use of these preparations in those with inhibitor levels <5 Bethesda units/mL.^{126 r s}

Has been used to induce immune tolerance to further suppress inhibitor production†.^{95 99 100 101 102 106 j} Such therapy eliminates risk of anamnesis with continued use of antihemophilic factor.^{95 99 100 101 102}

Generally should not be used for treatment of minor hemorrhage (e.g., cutaneous) in patients with inhibitors and a history of anamnestic response.^{95 106 108}

MASAC and other clinicians recommend use of a bypassing agent including activated prothrombin complex concentrate (APCC), recombinant factor VIIa, or prothrombin complex concentrates (PCCs) to prevent or control bleeding in patients with inhibitors.^{131 j}

Management of hemophilia A in patients with inhibitors may be difficult and consultation with a hemophilia treatment center is strongly recommended.^{55 74 79 85 95 126}

Acquired Hemophilia

Has been used to control bleeding in patients without hemophilia A who spontaneously acquire low levels of inhibitors (autoantibodies) to factor VIII.^{85 93 106} Autoantibodies are similar to but more heterogeneous than the alloantibodies that develop in patients with hemophilia A.^{28 31 55 61 67 88 90 93}

Management of acquired hemophilia† not well established.^{27 28 33 55 61 62 67 74 85 86 87 88 90 92 93 106} Antihemophilic factor (recombinant or human) may be effective in patients with low levels of inhibitors.^{78 85 88 92 95} Other treatment options include immunosuppressive therapy, desmopressin, or bypassing agents.^{27 30 31 33 55 61 62 67 77 85 86 88 92 93 94 95 106 124 125}

Antihemophilic Factor (Recombinant) Dosage and Administration

General

• 
  

  Confirm deficiency of factor VIII prior to initiating therapy.^{1 120 121 122 126}

  
  


• 
  

  Continue to monitor factor VIII periodically during treatment to individualize dosage and assess response to therapy.^{1 2 120 121 122 126} (See Laboratory Monitoring under Cautions.)

  
  

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by slow IV injection or IV infusion over several minutes.^{1 2 3 4 120 121 122}

Has been given as a continuous infusion†.^{m n o}

Instructions on reconstitution, dilution, and administration vary according to preparation; consult manufacturers’ labeling for specific information on each antihemophilic factor (recombinant) product.^{1 2 120 121 122}

Reconstitution

Prior to reconstitution, warm lyophilized powders and diluents supplied by the manufacturers to room temperature under ambient conditions (do not exceed 37°C).^{1 2 108 120 121 122}

Reconstitute and administer drug using tubing, administration sets, vial adapters, and filter needles provided by manufacturer.^{1 2 120 121 122} Use plastic syringes only; antihemophilic factor may adhere to glass.^{1 122}

Gently swirl solution to dissolve powder completely; do not shake vigorously.^{1 2 120 121 122}

Keep reconstituted solutions at room temperature and administer within 3 hours after reconstitution.^{1 2 121 122}

Rate of Administration

Individualize infusion rates according to patient response.^{1 2 120 121 122} Monitor pulse before and during infusion.^{1 122} Slow infusion rate or temporarily discontinue therapy if there is a substantial increase in pulse rate, or any other adverse reaction occurs.^{1 2 122}

Advate: Administer over 5 minutes or less.¹²²

Helixate FS, Kogenate FS: Administer over 5–10 minutes or less.^{120 121}

Recombinate: Administer at a rate ≤10 mL/minute.¹

ReFacto: Administer over several minutes; determine rate of administration by the patient’s comfort level.²

Dosage

Dosage expressed in terms of international units (IU, units).^{1 2 120 121 122} One unit is approximately equivalent to amount of factor VIII activity in 1 mL of fresh pooled normal human plasma.^{72 95 120 121}

Individualize dosage and duration of therapy based on degree of factor VIII deficiency (measuring factor VIII levels prior to and at regular intervals during therapy), desired factor VIII levels, patient’s weight, type and severity of bleeding, presence of inhibitors to factor VIII, and clinical response.^{1 2 55 120 121 122}

Use the following calculations and dosage guidelines (based on the degree of hemorrhage or type of surgery) for administering the drug.^{1 2 106 120 121 122} These calculations and suggested dosage regimens are only approximations and should not preclude appropriate laboratory determinations of factor VIII levels.^{1 2 55 120 121 122} Perform serial assays of factor VIII at suitable intervals as needed to ensure that adequate levels have been attained and maintained.^{1 122} (See Laboratory Monitoring under Cautions.)

If calculated dosage is ineffective in achieving expected factor VIII levels or if bleeding is not controlled, consider the possibility that inhibitors to antihemophilic factor may have developed.^{1 120 121 122} (See Development of Inhibitors to Antihemophilic Factor under Cautions.) Higher dosages may be required in such situations.^{1 2 120 122}

Administration of 1 unit/kg antihemophilic factor (recombinant) generally increases factor VIII activity by approximately 2%.^{2 48 55 74 126}

Dosage required to achieve desired factor VIII levels:^{1 2 120 121}

Dose (units) = body weight (in kg) × 0.5 × desired factor VIII increase (in % of normal)

Approximate % increase in factor VIII levels expected from a given dosage:^{1 120 121}

Expected factor VIII increase (in % of normal) = [dose (units)/body weight (in kg)] × 2

Pediatric Patients

Hemophilia A

Advate

IV

Children ≥1 month of age with early hemarthrosis, muscle hemorrhage, or oral bleeding: Use appropriate dosage to achieve a plasma factor VIII level of 20–40% of normal; repeat every 12–24 hours for 1–3 days until bleeding resolves (indicated by pain relief) or healing occurs.¹²²

Children ≥1 month of age with more extensive hemarthrosis, muscle hemorrhage, or hematoma: Use appropriate dosage to achieve a plasma factor VIII level of 30–60% of normal; repeat every 12–24 hours for ≥3 days until pain and disability resolve.¹²²

Children ≥1 month of age with life-threatening bleeding (e.g., head injury, throat bleeding, severe abdominal pain): Use appropriate dosage to achieve a plasma factor VIII level of 60–100% of normal; repeat every 8–24 hours until bleeding resolves.¹²²

Children ≥1 month of age undergoing minor surgery (e.g., tooth extraction): Use appropriate dosage to achieve a plasma factor VIII level of 60–100% of normal within 1 hour of surgery.¹²² Repeat dose every 12–24 hours as needed.¹²² Consider adjunctive therapy for dental procedures.¹²²

Children ≥1 month of age undergoing major surgery: Use appropriate dosage to achieve pre- and postoperative factor VIII levels of 80–120% of normal.¹²² Repeat dose every 8–24 hours to desired factor VIII activity and state of wound healing.¹²²

Helixate FS and KogenateFS

IV

Children of any age with minor hemorrhage (e.g., superficial, early hemorrhages, bleeding into joints): Initially, 10–20 units/kg to achieve a plasma factor VIII level of 20–40% of normal; repeat if bleeding continues.^{120 121}

Children of any age with moderate to major hemorrhage (hemorrhage into muscles or oral cavity; definite hemarthroses; known trauma): Initially, 15–30 units/kg to achieve a plasma factor VIII level of 30–60% of normal; repeat once at 12–24 hours, if needed.^{120 121}

Children of any age with major to life-threateninghemorrhage (intracranial, intra-abdominal, or intrathoracic hemorrhages; GI bleeding; CNS bleeding; bleeding in retropharyngeal or retroperitoneal spaces or iliopsoas sheath), fractures, head trauma: Initially, 40–50 units/kg to achieve a plasma factor VIII level of 80–100% of normal; give additional doses of 20–25 units/kg every 8–12 hours.^{120 121}

Children of any age undergoing minor surgery: Initially, 15–30 units/kg to achieve a plasma factor VIII level of 30–60% of normal; repeat once at 12–24 hours, if needed.^{120 121}

Children of any age undergoing major surgery: Initially, 50 units/kg preoperatively to achieve a plasma factor VIII level of approximately 100% of normal (must verify 100% factor activity prior to surgery); may repeat after 6–12 hours initially, and for 10–14 days until healing complete.^{120 121}

Children of any age: For prophylaxis of bleeding, may administer on a regular schedule.^{120 121}

Recombinate

IV

Children of any age with early hemarthrosis, muscle hemorrhage, or oral bleeding: Use appropriate dosage to achieve a plasma factor VIII level of 20–40% of normal; repeat every 12–24 hours for 1–3 days until bleeding resolves (indicated by pain relief) or healing occurs.¹

Children of any age with more extensive hemarthrosis, muscle hemorrhage, or hematoma: Use appropriate dosage to achieve a plasma factor VIII level of 30–60% of normal; repeat every 12–24 hours for ≥3 days until pain and disability resolve.¹

Children of any age with life-threatening bleeding (e.g., head injury, throat bleeding, severe abdominal pain): Use appropriate dosage to achieve a plasma factor VIII level of 60–100% of normal; repeat every 8–24 hours until bleeding resolves.¹

Children of any age undergoing minor surgery (including tooth extraction): Use appropriate dosage to achieve a plasma factor VIII level of 60–80% of normal.¹ A single infusion in conjunction with oral antifibrinolytic therapy within 1 hour usually sufficient in about 70% of patients.¹

Children of any age undergoing major surgery: Use appropriate dosage to achieve plasma pre- and postoperative factor VIII levels of 80–100% of normal.¹ Repeat dose every 8–24 hours to desired factor VIII activity and state of wound healing.¹

ReFacto

IV

Children of any age with minor hemorrhage (early hemarthrosis, minor muscle hemorrhage, oral bleeding): Use appropriate dosage to achieve a plasma factor VIII level of 20–40% of normal; repeat every 12–24 hours as needed until bleeding resolves.² Give at least 1 day of therapy (depending on the severity of hemorrhage).²

Children of any age with moderate hemorrhage (muscle hemorrhage, mild trauma capitis, hemorrhage into oral cavity): Use appropriate dosage to achieve a plasma factor VIII level of 30–60% of normal; repeat infusions every 12–24 hours for 3–4 days until local hemostasis achieved.²

Children of any age with major hemorrhage (GI, intracranial, intra-abdominal, or intrathoracic hemorrhages) or fractures: Use appropriate dosage to achieve a plasma factor VIII level of 60–100% of normal; repeat every 8–24 hours until bleeding resolves.²

Children of any age undergoing minor surgery (e.g., tooth extraction): Use appropriate dosage to achieve a plasma factor VIII level of 30–60% of normal; repeat infusions every 12–24 hours for 3–4 days until local hemostasis achieved.² For tooth extraction, a single infusion in conjunction with oral antifibrinolytic therapy within 1 hour may be sufficient.²

Children of any age undergoing major surgery: Use appropriate dosage to achieve a plasma factor VIII level of 60–100% of normal; repeat every 8–24 hours until local hemostasis achieved.²

Children of any age with hemophilia A receiving short-term routine prophylaxis (to prevent or reduce frequency of spontaneous bleeding episodes): Manufacturer recommends administration of drug at least twice weekly to prevent spontaneous musculoskeletal hemorrhages; shorter dosage intervals or higher dosages may be necessary in some pediatric patients.² Manufacturer also states that routine prophylaxis 3 times weekly may be associated with a lower risk of bleeding than a twice-weekly regimen.² In addition, some experts state that optimum dosage and dosage regimen for short-term routine prophylaxis have not been established.¹²⁶

Adults

Hemophilia A

Advate

IV

Early hemarthrosis, muscle hemorrhage, or oral bleeding: Use appropriate dosage to achieve a plasma factor VIII level of 20–40% of normal; repeat every 12–24 hours for 1–3 days until bleeding resolves (indicated by pain relief) or healing occurs.¹²²

More extensive hemarthrosis, muscle hemorrhage, or hematoma: Use appropriate dosage to achieve a plasma factor VIII level of 30–60% of normal; repeat every 12–24 hours for ≥3 days until pain and disability resolve.¹²²

Life-threatening bleeding (e.g., head injury, throat bleeding, severe abdominal pain): Use appropriate dosage to achieve a plasma factor VIII level of 60–100% of normal; repeat every 8–24 hours until bleeding resolves.¹²²

Minor surgery (e.g., tooth extraction): Use appropriate dosage to achieve a plasma factor VIII level of 60–100% of normal within 1 hour of surgery.¹²² Repeat dose every 12–24 hours as needed.¹²² Consider adjunctive therapy for dental procedures.¹²²

Major surgery: Use appropriate dosage to achieve pre- and postoperative plasma factor VIII levels of 80–120% of normal.¹²² Repeat dose every 8–24 hours to desired factor VIII activity and state of wound healing.¹²²

Helixate FS and KogenateFS

IV

Minor hemorrhage (e.g., superficial, early hemorrhages, bleeding into joints): Initially, 10–20 units/kg to achieve factor VIII level of 20–40% of normal; repeat if bleeding continues.^{120 121}

Moderate to major hemorrhage (hemorrhage into muscles or oral cavity; definite hemarthroses; known trauma): Initially, 15–30 units/kg to achieve a factor VIII level of 30–60% of normal; repeat once at 12–24 hours, if needed.^{120 121}

Major to life-threatening hemorrhage (intracranial, intra-abdominal, or intrathoracic hemorrhages; GI bleeding; CNS bleeding; bleeding in retropharyngeal or retroperitoneal spaces or iliopsoas sheath), fractures, head trauma: Initially, 40–50 units/kg to achieve a plasma factor VIII level of 80–100% of normal; give additional dosages of 20–25 units/kg every 8–12 hours.^{120 121}

Minor surgery: Initially, 15–30 units/kg to achieve a plasma factor VIII level of 30–60% of normal; repeat once at 12–24 hours, if needed.^{120 121}

Majorsurgery: Initially, 50 units/kg preoperatively to achieve a factor VIII level of approximately 100% of normal (must verify 100% factor activity prior to surgery); may repeat every 6–12 hours initially, and for 10–14 days until healing complete.^{120 121}

For prophylaxis of bleeding, may administer on a regular schedule.^{120 121}

Recombinate

IV

Early hemarthrosis, muscle hemorrhage, or oral bleeding: Use appropriate dosage to achieve a factor VIII level of 20–40% of normal; repeat every 12–24 hours for 1–3 days until bleeding resolves (indicated by pain relief) or healing occurs.¹

More extensive hemarthrosis, muscle hemorrhage, or hematoma: Use appropriate dosage to achieve a plasma factor VIII level of 30–60% of normal; repeat every 12–24 hours for ≥3 days until pain and disability resolve.¹

Life-threatening bleeding (e.g., head injury, throat bleeding, severe abdominal pain): Use appropriate dosage to achieve a plasma factor VIII level of 60–100% of normal; repeat every 8–24 hours until bleeding resolves.¹

Minor surgery (including tooth extraction): Use appropriate dosage to achieve a plasma factor VIII level of 60–80% of normal.¹ A single infusion in conjunction with oral antifibrinolytic therapy within 1 hour usually sufficient in about 70% of patients.¹

Major surgery: Use appropriate dosage to achieve pre- and postoperative plasma factor VIII levels of 80–100% of normal.¹ Repeat dose every 8–24 hours to desired factor VIII level and state of wound healing.¹

ReFacto

IV

Minor hemorrhage (early hemarthrosis, minor muscle hemorrhage, oral bleeding): Use appropriate dosage to achieve a plasma factor VIII level of 20–40% of normal; repeat every 12–24 hours until bleeding resolves.² Give at least 1 day of therapy (depending on the severity of hemorrhage).²

Moderate hemorrhage (muscle hemorrhage, mild trauma capitis, hemorrhage into oral cavity): Use appropriate dosage to achieve a plasma factor VIII level of 30–60% of normal; administer infusions every 12–24 hours for 3–4 days until local hemostasis achieved.²

Major hemorrhage (GI, intracranial, intra-abdominal, or intrathoracic hemorrhages), fractures: Use appropriate dosage to achieve a plasma factor VIII level of 60–100% of normal; repeat every 8–24 hours until local hemostasis achieved.²

Minor surgery (e.g., tooth extraction): Use appropriate dosage to achieve a plasma factor VIII level of 30–60% of normal; administer infusions every 12–24 hours for 3–4 days until local hemostasis achieved.² For tooth extraction, a single infusion in conjunction with oral antifibrinolytic therapy within 1 hour may be sufficient.²

Major surgery: Use appropriate dosage to achieve a factor VIII level of 60–100% of normal; repeat every 8–24 hours until local hemostasis achieved.²

Adults with hemophilia A receiving short-term routine prophylaxis (to prevent or reduce frequency of spontaneous bleeding episodes): Manufacturer recommends administration of drug at least twice weekly to prevent spontaneous musculoskeletal hemorrhages; shorter dosage intervals or higher dosage may be necessary in some patients.² Manufacturer also states that routine prophylaxis 3 times weekly may be associated with a lower risk of bleeding than a twice-weekly regimen.² Some experts state that optimum dosage and dosage regimen for short-term routine prophylaxis have not been established.¹²⁶

Prescribing Limits

Pediatric Patients

Hemophilia A

IV

Maximum infusion rate of 10 mL/minute.^{1 122}

Adults

Hemophilia A

IV

Maximum infusion rate of 10 mL/minute.^{1 122}

Cautions for Antihemophilic Factor (Recombinant)

Contraindications

• 
  

  Known hypersensitivity to antihemophilic factor (recombinant) or any ingredient in the formulation.^{120 121 122}

  
  


• 
  

  Known hypersensitivity to murine or hamster proteins (Advate, Helixate FS, KogenateFS, Recombinate, ReFacto)^{1 2 120 121 122} or bovine proteins (Recombinate).¹

  
  

Warnings/Precautions

Warnings

Prior to initiation of antihemophilic factor (recombinant) therapy, appropriate laboratory tests should be performed to confirm that a deficiency in factor VIII exists.^{1 120 121 122 126}

Development of Inhibitors to Antihemophilic Factor

Risk of development of inhibitors (alloantibodies) to factor VIII following antihemophilic factor therapy.^{1 2 4 5 13 29 39 46 69 76 89 120 121 122 126 k} Risk of inhibitor development appears to correlate with the severity of hemophilia A and extent of exposure to the drug.^{27 57 59 61 62 89 95 98 101 102 104} Inhibitors usually identified in patients <20 years of age; those <10 years of age appear to be at greatest risk of developing such antibodies.^{27 57 58 59 62 63 95 98 104 106}

Inhibitors reported in about 10–30% of patients with hemophilia A,^{1 120 122 126} usually within the first 10–20 days of treatment.^{76 120 126 k} Inhibitors may diminish or neutralize response to therapy.^{1 2 k} Anamnestic response and increased levels of inhibitor possible with continued use of drug.¹

Monitor for development of inhibitors during treatment with clinical observation and appropriate laboratory tests.^{1 2 27 28 55 65 67 74 91 95 120 121 122} Perform quantitative test (e.g., Bethesda assay) for inhibitors routinely (e.g., every 3–6 months) and prior to surgery.^{23 55 56 60 66 74 106 126} Screen children every 3–12 months or every 10–20 days following drug exposure, whichever occurs first.¹²⁶ Consider the possibility that inhibitors may have developed in patients with treatment failure despite adequate dosages of antihemophilic factor (recombinant) or those with unusually prolonged aPTT.^{1 27 61 65 74 95 120 121 122 k}

Consider several factors (e.g., severity and location of bleeding, type and titer of inhibitors, history of anamnestic response, product availability) when treating patients with inhibitors.^{26 27 55 62 67 74 77 79 85 95 126 127} Consultation with a hemophilia treatment center strongly recommended.^{79 126} Carefully monitor such patients, especially when surgical procedures indicated.^{1 55 60 74 79 85 95 126} Dosage requirements may be variable; use clinical response and factor VIII levels to guide treatment.^{2 120 121 122}

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., hives, generalized urticaria, tightness of the chest, wheezing, hypotension, anaphylaxis) reported rarely with some recombinant factor VIII preparations.^{120 121}

If hypersensitivity reaction occurs, discontinue drug immediately and initiate appropriate therapy (e.g., epinephrine, oxygen).^{1 2 120 121 122}

Antibody Formation

Some preparations of antihemophilic factor (recombinant) contain trace amounts of animal proteins (Advate, Kogenate, Recombinate, ReFacto) which may stimulate antibody production and cause hypersensitivity reactions.^{1 2 120 121 122} Antibodies to such animal proteins reported in a few patients; effect on clinical response not fully elucidated.^{40 45}

Latex Sensitivity

Packaging components for some preparations (e.g., Recombinate) may contain natural latex proteins; take appropriate precautions if injection is handled by or administered to individuals with a history of natural latex sensitivity.^{1 p q}

General Precautions

Risk of Transmissible Agents

Since antihemophilic factor (recombinant) preparations are not prepared using pooled human plasma, they are associated with a decreased risk of transmission of human viruses compared with risk associated with plasma-derived antihemophilic factor (human).^{3 4 8 9 14 40 49 52 55 69 73 76 79 110}

Theoretic but remote risk of transmitting other viruses (e.g., those associated with mammalian cell cultures employed in manufacturing).^{40 49 79 106 108 110} No such transmission reported to date.^{79 110}

Laboratory Monitoring

Use under supervision of a qualified clinician experienced in treating hemophilia A.^{1 2 122}

Monitor factor VIII levels prior to and at regular intervals during therapy to guide dosing and ensure adequate therapeutic response.^{1 2 55 120 121 122}

Monitor factor VIII levels when switching between different factor VIII preparations.²

Monitor for development of inhibitors (with Bethesda assay) during treatment, prior to surgery, and when switching between different factor VIII preparations.^{1 27 28 55 65 67 74 91 95 126} (See Development of Inhibitors to Antihemophilic Factor under Cautions.)

Sucrose Content

Helixate FS and Kogenate FS (250-, 500-, and 1000-unit vials) contain 28 mg of sucrose per vial, while Kogenate FS 2000-unit vials contain 56 mg of sucrose.^{120 121} The manufacturers state that IV administration of these injections will not affect blood glucose concentrations.^{120 121}

Specific Populations

Pregnancy

Category C.^{1 2 120 121 122}

Lactation

Not known whether antihemophilic factor (recombinant) is distributed into human milk.^{b f g} Use only if clearly indicated.^{120 121 c}

Pediatric Use

Advate: Safety and efficacy not established in children <1 month of age.¹²²

Helixate FS, Kogenate FS, Recombinate, ReFacto: Have been used in children of all ages without any unusual adverse effects.^{1 2 4 5 47 120 121}

Infusion-related reactions (e.g., urticaria, flushing, erythema) occur rarely in previously untreated neonates and children following administration of recombinant factor VIII.^{5 106 108}

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.²