Antihemophilic Factor [Factor VIII]

Approved Indications:

• Hemophilia A (Congenital Factor VIII Deficiency):
• Prophylaxis: Routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes.
• On-demand Treatment: Control and prevention of bleeding episodes, including spontaneous and trauma-induced bleeds.
• Perioperative Management: Prevention and control of bleeding during and after surgical procedures.

Clinically Accepted Off-label Uses:

• Acquired Hemophilia A:
  In rare cases, recombinant Factor VIII may be considered under expert supervision for bleeding management in patients who develop autoantibodies against Factor VIII, though bypassing agents are usually preferred.

Dosage Calculation Formula:
Dosage (IU) = Body weight (kg) × Desired FVIII rise (%) × 0.5

Adults and Children:

• On-Demand Bleeding Treatment:
• Mild bleeding (e.g., early joint bleed): 20–40 IU/kg
• Moderate bleeding (e.g., muscle bleed): 30–60 IU/kg
• Severe bleeding (e.g., CNS, GI bleed): 60–100 IU/kg
• Surgical Prophylaxis:
• Minor surgery: 30–60 IU/kg pre-op and every 12–24 hrs for 1–3 days post-op.
• Major surgery: 60–100 IU/kg pre-op; then 40–60 IU/kg every 8–24 hrs for up to 14 days post-op.
• Routine Prophylaxis:
• Adults and adolescents: 20–40 IU/kg every other day or 3 times per week.
• Children (<12 years): 25–50 IU/kg 2–3 times per week or every other day.

Elderly:

• Same as adult dosing, with close monitoring for comorbidities.

Renal/Hepatic Impairment:

• No specific dose adjustment required, but monitor for hypersensitivity or inhibitor development.

Administration:

• Administer intravenously over several minutes (usually 2–5 minutes) or as a continuous infusion in a hospital setting.
• May be self-administered at home after proper training.
• Do not mix with other intravenous medications.

Antihemophilic Factor [Factor VIII] is a glycoprotein that plays a critical role in the intrinsic pathway of blood coagulation. Upon activation (Factor VIIIa), it forms a complex with activated Factor IX (IXa) on the phospholipid surfaces of platelets. This complex accelerates the conversion of Factor X to Xa, which subsequently leads to the transformation of prothrombin into thrombin. Thrombin then converts fibrinogen to fibrin, forming a stable clot. In patients with Hemophilia A, administration of exogenous Factor VIII restores the clotting cascade, effectively controlling or preventing bleeding episodes.

• Absorption: Not applicable (IV administration).
• Bioavailability: 100% after intravenous administration.
• Distribution: Confined primarily to intravascular compartment.
• Time to Peak: Immediate after IV injection.
• Half-life:
• Standard FVIII products: 8–12 hours
• Extended half-life FVIII: 14–19 hours
• Metabolism: Proteolytically degraded by plasma proteases.
• Excretion: Cleared mainly via hepatic catabolism; renal excretion is minimal.

• Pregnancy:
  No official FDA pregnancy category; limited human data available. Use only if clearly needed. Animal studies show no fetal harm, but cautious use is recommended, especially in high doses or surgical settings.
• Lactation:
  Unknown whether Factor VIII is excreted into human milk. Due to high molecular weight, systemic absorption by the infant is unlikely. However, use with caution and monitor the infant for any adverse effects if breastfeeding is continued.

• Primary Class: Antihemorrhagic Agent
• Subclass: Recombinant Clotting Factor / Coagulation Factor VIII Replacement
• Generation:
• First-generation: Human albumin-stabilized
• Second-generation: No human/animal proteins added during production
• Third-generation & beyond: Fully recombinant, stabilized with non-human proteins or PEGylated (extended half-life)

• Known hypersensitivity to Factor VIII or its components (e.g., hamster protein in some products)
• History of severe allergic reactions or anaphylaxis to Factor VIII products
• Patients with known Factor VIII inhibitors (use bypassing agents instead)

• Inhibitor Development:
• Monitor all patients for development of neutralizing antibodies (inhibitors), especially previously untreated patients (PUPs).
• Hypersensitivity Reactions:
• Includes urticaria, dyspnea, hypotension, and anaphylaxis. Discontinue immediately if suspected.
• Thrombosis Risk:
• Though rare, thrombotic events (e.g., DVT, PE) may occur, particularly with high doses or prolonged use.
• Monitoring Requirements:
• Factor VIII activity levels (before and after dosing)
• Inhibitor screening periodically
• Elderly and Comorbid Patients:
• Monitor closely due to increased risk of cardiovascular events.

Common Side Effects (≥1%):

• Headache
• Fever (pyrexia)
• Nausea
• Injection site reaction
• Dizziness
• Arthralgia or myalgia

Serious but Less Common (<1%):

• Anaphylactic reactions
• Inhibitor development (neutralizing antibodies)
• Thrombosis (especially with extended half-life products)
• Hypotension, bronchospasm

Rare Side Effects:

• Hemolysis
• Nephrotic syndrome (linked with immune complex formation)
• Lymphadenopathy

Timing & Severity:

• Infusion-related reactions typically occur during or within 1 hour of administration.
• Inhibitor development is gradual and may occur after several exposures (especially in children or previously untreated patients).

• Drug–Drug Interactions:
  No known significant drug-drug interactions.
• Drug–Food Interactions:
  Not applicable.
• Drug–Alcohol Interactions:
  Not reported; no interaction expected.
• Enzyme Systems:
  Not metabolized via CYP450; does not induce or inhibit hepatic enzymes.

Note: Use of hemostatic agents or antifibrinolytics (e.g., tranexamic acid) concurrently may increase clotting risk—monitor for thrombosis.

• WFH Guidelines (2024):
  Recommend early prophylaxis with Factor VIII in children with severe hemophilia A to prevent joint disease.
• EMA & FDA Updates (2023):
  Approval of new extended half-life (EHL) Factor VIII molecules with reduced infusion frequency (e.g., once weekly).
• ISTH Guidelines:
  Emphasize routine inhibitor screening, particularly in the first 50 exposure days in PUPs.
• Gene Therapy Developments:
  While gene therapy is emerging, Factor VIII replacement remains standard care for most patients globally.

• Refrigerated Products (Standard):
  Store between 2°C and 8°C. Do not freeze.
• Room Temperature Stability (varies by product):
  Many products can be kept at ≤25°C for up to 6–12 months. Always refer to specific brand labeling.
• Protection:
  Protect from light. Keep vial in outer carton until use.
• After Reconstitution:
• Use within 3 hours if stored at room temperature.
• Do not refrigerate after reconstitution.
• Do not shake; swirl gently to dissolve.