Emicizumab

Approved Indications:

• Hemophilia A with Factor VIII Inhibitors:
  Indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients with congenital hemophilia A who have developed inhibitors to factor VIII.
• Hemophilia A without Factor VIII Inhibitors:
  Indicated for routine prophylaxis in adult and pediatric patients with hemophilia A, with or without factor VIII inhibitors, to prevent or reduce bleeding episodes.

Important Off-Label (Clinically Accepted) Uses:

• Management of perioperative bleeding prophylaxis in hemophilia A patients with inhibitors (off-label in some regions).
• Use in adolescents transitioning from pediatric care when frequent factor VIII infusions are impractical.

Prophylactic Dosing (Subcutaneous):

• Loading Dose: 3 mg/kg once weekly for 4 weeks.
• Maintenance Dose Options (after loading):
• 1.5 mg/kg once weekly or
• 3 mg/kg every two weeks or
• 6 mg/kg every four weeks
• Special Populations:
• Pediatrics: Dosing based on body weight; same regimen applies.
• Renal or Hepatic Impairment: No dose adjustment necessary.
• Elderly: No specific adjustment; monitor comorbidities.

Administration Notes:

• Subcutaneous injection in the abdomen, thigh, or upper arm.
• Rotate injection sites to reduce local reactions.
• Administer using a prefilled syringe or autoinjector as provided.
• Do not mix with other medications in the same syringe.

Emicizumab is a recombinant, humanized, bispecific monoclonal antibody that binds to activated factor IX (FIXa) and factor X (FX), mimicking the cofactor function of activated factor VIII (FVIIIa). By bridging FIXa and FX, it promotes the activation of FX, facilitating thrombin generation and clot formation even in the absence of endogenous FVIII. This bypasses the inhibitory effect of factor VIII inhibitors and restores hemostasis in hemophilia A patients.

• Absorption: Subcutaneous bioavailability ~80%; peak plasma concentration reached in 7–14 days after initial dose.
• Distribution: Volume of distribution ~7.9 L; primarily confined to plasma.
• Metabolism: Catabolized via proteolytic pathways; no significant CYP450 involvement.
• Elimination: Half-life approximately 28 days; steady-state concentrations achieved within 4–6 weeks of repeated dosing. Excreted mainly via reticuloendothelial system; minimal renal clearance.

• Pregnancy: Human data are limited; animal studies have not shown fetal harm. Use only if the potential benefit justifies the risk.
• Lactation: It is unknown whether Emicizumab is excreted in human milk. Caution is advised, and breastfeeding is generally not recommended during therapy.
• General Recommendation: Avoid during pregnancy and lactation unless clinically necessary; monitor maternal and neonatal outcomes.

• Primary Class: Hemostatic agent
• Subclass: Monoclonal antibody, bispecific factor VIII mimetic

• Known hypersensitivity to Emicizumab or any excipients
• Active thromboembolic disease (relative caution; monitor closely)
• Severe uncontrolled infections or conditions where immune modulation may pose risk

• Thrombotic Microangiopathy (TMA): Rare, primarily when high doses of activated prothrombin complex concentrate are co-administered.
• Thrombosis Risk: Monitor for signs of venous or arterial thrombosis.
• Injection Site Reactions: Common; rotate sites and monitor for erythema, swelling, or pain.
• Immune Response: Development of anti-drug antibodies (ADA) is possible; monitor for loss of efficacy.
• Monitoring: Regular assessment of bleeding episodes and factor VIII activity is recommended.
• Surgery & Invasive Procedures: Dose adjustment or additional hemostatic agents may be required perioperatively.

Common Adverse Effects:

• Injection site reactions: redness, swelling, pain
• Headache
• Fatigue
• Arthralgia

Serious or Rare Adverse Effects:

• Thrombosis
• Thrombotic microangiopathy (TMA)
• Hypersensitivity reactions including anaphylaxis
• Development of anti-emicizumab antibodies leading to reduced efficacy

Timing and Severity:

• Injection site reactions usually occur within hours to days after injection.
• Serious thrombotic events are rare but may occur at any time, particularly with concomitant bypassing agents.

• Activated Prothrombin Complex Concentrate (aPCC): High doses (>100 U/kg/day for ≥24 hours) increase risk of thrombotic microangiopathy and thrombosis.
• Bypassing Agents: Use caution; monitor coagulation parameters.
• Other Anticoagulants or Antiplatelets: Increased risk of bleeding or thrombosis; close monitoring recommended.
• CYP450 Metabolism: No significant interactions as Emicizumab is metabolized via proteolysis, not CYP pathways.

• FDA 2023 Update: Expanded prophylactic indication to include pediatric patients under 12 months in certain countries.
• WHA & ISTH Guidance: Recommend Emicizumab as first-line prophylaxis for hemophilia A with inhibitors due to ease of use and efficacy.
• Perioperative Management: Updated guidelines now provide detailed recommendations for using Emicizumab during surgery, emphasizing careful hemostatic planning.

• Temperature: Store at 2°C to 8°C (36°F to 46°F).
• Do Not Freeze: Protect from freezing.
• Light: Keep in original carton to protect from light.
• Handling: Prefilled syringes or autoinjectors may be kept at room temperature (≤30°C) for up to 7 days prior to injection.
• Reconstitution: Not required; ready-to-use formulation.