Human coagulation factor VIII

Usage

• Human coagulation factor VIII is prescribed for the treatment and prophylaxis of bleeding in patients with Hemophilia A (congenital Factor VIII deficiency). It is also used to manage bleeding associated with surgical procedures in these patients. Some formulations are used in von Willebrand disease.
• Pharmacological classification: Hemostatic agent, Coagulation factor.
• Mechanism of Action: Factor VIII is an essential clotting factor that works by binding to von Willebrand factor. This complex is crucial for the activation of Factor X, which ultimately leads to the conversion of prothrombin to thrombin and the formation of a stable fibrin clot, stopping bleeding.

Alternate Names

• Antihemophilic factor (AHF)

• Recombinant Factor VIII

• Octocog alfa (rDNA), Moroctocog alfa (rDNA), and others refer to specific recombinant forms.

• Brand names: XYNTHA, ADVATE, ELOCTATE, Kovaltry, Wilate, and others.

How It Works

• Pharmacodynamics: Replaces deficient or defective Factor VIII, restoring normal coagulation cascade function.
• Pharmacokinetics:
  • Administered intravenously.
  • Absorption: Immediate and complete bioavailability upon intravenous administration.
  • Distribution: Distributes into the intravascular compartment.
  • Metabolism: Factor VIII is naturally degraded in the body. Specific details on metabolic pathways are not fully elucidated.
  • Elimination: Half-life varies, typically 8-12 hours, but can range from 5 to 22 hours, potentially requiring frequent dosing. Elimination pathways are not fully characterized.
• Mode of Action: Factor VIII binds to von Willebrand factor in circulation, forming a complex that interacts with Factor IXa. This complex activates Factor X, a key step in the coagulation cascade leading to fibrin clot formation. No direct receptor binding or enzyme inhibition is involved.

Dosage

Standard Dosage

Adults:

Dosage is individualized based on patient needs and the severity and location of bleeding. Dosing is based on Factor VIII activity levels (IU/dL or % of normal) and body weight (kg). General dosage calculation: Required units = body weight (kg) x desired Factor VIII rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL)

Children:

• Similar dosing calculations as adults, but may require higher or more frequent doses due to differences in pharmacokinetics (faster clearance).
• Prophylactic dosing: Children under 6 years old often receive 25-50 IU/kg twice a week or every 3-4 days, while older children follow adult dosing guidelines.

Special Cases:

• Elderly Patients: Individualized dosing. Start with lower doses due to the increased frequency of reduced hepatic, renal, or cardiac function and potential concomitant diseases.
• Patients with Renal Impairment: No specific dose modifications are universally established. Exercise caution and monitor closely.
• Patients with Hepatic Dysfunction: No specific dose modifications are universally established. Exercise caution and monitor closely.
• Patients with Comorbid Conditions: Individualized dosing based on clinical condition.

Clinical Use Cases

Dosing adjustments are needed in specific clinical settings, such as:

• Hemorrhage: Dose according to severity (e.g. mild, moderate, or severe) and location.
• Surgical Procedures: Pre- and post-operative dosing to maintain adequate factor VIII levels.
• Prophylaxis: Administer 20–50 IU/kg every 2–3 days or as needed to prevent bleeding.

Dosage Adjustments:

Individualized dosing is crucial. Adjust according to patient’s clinical response, Factor VIII levels, and individual pharmacokinetic parameters (half-life, recovery).

Side Effects

Common Side Effects

• Headache
• Fever (pyrexia)
• Development of inhibitors (neutralizing antibodies) to Factor VIII
• Local injection site reactions (stinging, inflammation)

Rare but Serious Side Effects

• Allergic reactions, including anaphylaxis (rare but serious)
• Neutralizing antibodies to factor VIII (inhibitors).

Contraindications

• Known hypersensitivity to Factor VIII, any component of the formulation, or hamster proteins (in some recombinant products).

Drug Interactions

No specific drug interactions have been definitively documented.

Pregnancy and Breastfeeding

• Pregnancy: Limited data are available. Use only if clearly indicated. Monitor closely.
• Breastfeeding: Limited information on excretion in breast milk. Generally considered safe, as factor VIII is a large protein and likely poorly absorbed by infants.

Drug Profile Summary

• Mechanism of Action: Replaces deficient Factor VIII to restore coagulation cascade function.
• Side Effects: Headache, fever, inhibitor development, injection site reactions, rarely anaphylaxis.
• Contraindications: Hypersensitivity to Factor VIII or formulation components.
• Drug Interactions: No clinically significant interactions established.
• Pregnancy & Breastfeeding: Limited data. Use only if clearly indicated.
• Dosage: Individualized based on bleeding severity and location.
• Monitoring Parameters: Factor VIII activity levels, bleeding status, signs of hypersensitivity.

Popular Combinations

• Often used with von Willebrand factor in some formulations.
• May be given with antifibrinolytic agents in specific clinical situations like dental extractions.

Precautions

• Monitor Factor VIII levels during therapy.
• Assess for hypersensitivity reactions.
• Inhibitor development can occur.
• Administer slowly by intravenous infusion to minimize side effects.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Human coagulation factor VIII?

A: Dosage is individualized based on bleeding severity, location, and patient-specific factors like age, weight, and response.

Q2: How is human coagulation factor VIII administered?

A: Intravenously. Intravenous bolus or slow infusion.

Q3: What are the common side effects?

A: Headache, fever, development of inhibitors, local reactions at the injection site.

Q4: What are the serious side effects?

A: Allergic reactions, including rare cases of anaphylaxis. Also development of inhibitors.

Q5: Are there any drug interactions I should be aware of?

A: No significant drug interactions have been reported.

Q6: Can human coagulation factor VIII be used during pregnancy and breastfeeding?

A: Limited data exists. Use cautiously and only if the potential benefits outweigh the potential risks. Not contraindicated in breastfeeding.

Q7: How do I monitor a patient on human coagulation factor VIII?

A: Regularly monitor Factor VIII activity levels and observe for signs of bleeding or hypersensitivity reactions.

Q8: What is an inhibitor and why is it a concern?

A: An inhibitor is a neutralizing antibody that the body can develop against Factor VIII. This makes the treatment less effective. Inhibitor titers should be assessed if bleeding is not controlled with usual doses.

Q9: What are the different types of factor VIII products available?

A: Plasma-derived and recombinant factor VIII products.

Q10: What is the difference between plasma-derived and recombinant factor VIII?

A: Plasma-derived factor VIII is purified from human plasma, while recombinant factor VIII is produced in a laboratory setting using genetic engineering. Recombinant factor VIII generally carries a lower risk of transmitting bloodborne viruses.