Emicizumab injection has been developed by Chugai and is marketed by the brand name of "Hemlibra''. It is indicated for the treatment of patients with Hemophilia A with or without factor VIII inhibitors.

Emicizumab (Hemlibra) Uses:

• Prophylaxis of Hemophilia A:

  • It is indicated for routine prophylaxis of patients with hemophilia A to prevent or reduce the frequency of bleeding episodes.
  • Because of its unique mechanism of action, It can be. administered to patients who have developed antibodies or inhibitors to factor VIII.

Adult dose:

Emicizumab (Hemlibra) Dose in the prophylaxis of Hemophilia A in Adults:

• Initial: 3 mg/kg administered subQ once a week for 4 weeks
• Maintenance:
  • 5 mg/kg administered subQ once a week or
  • 3 mg/kg subQ administered once every 2 weeks or
  • 6 mg/kg subQ administered once every 4 weeks

Note:

• The use of prophylactic factor VIII may be continued during the first week of therapy, however, the prophylactic use of factor VIII inhibitors should be discontinued one day prior to initiating the treatment.

Dose in children:

Emicizumab (Hemlibra) Dose in the prophylaxis of Hemophilia A in Children:

Note:

• The use of prophylactic factor VIII may be continued during the first week of therapy, however, the prophylactic use of factor VIII inhibitors should be discontinued one day prior to initiating the treatment.

• Infants, Children, and Adolescents:

  • Initial loading dose:
    • 3 mg/kg subQ administered once a week for the first 4 weeks (a total of 4 doses)
  • Maintenance therapy:
    • 1.5 mg/kg administered subQ once a week or
    • 3 mg/kg administered subQ once every two weeks or
    • 6 mg/kg administered subQ once every four weeks

Emicizumab (Hemlibra) Pregnancy Risk Category: C

• • • • Human pregnant women have not been tested with the drug.
      • Placental excretion, however, is possible, especially in the third trimester, just like endogenous immunoglobulins.
      • The manufacturer suggests effective contraception for females in their reproductive years.

  Emicizumab use during breastfeeding:

  • • It is unknown if the drug will be excreted into breastmilk.
    • It is possible to excrete the drug from breastmilk because it is a. humanized monoclonal IgG immunoglobulin.
    • Manufacturers recommend weighing the risks to the infant from drug exposure, breastfeeding's benefits, and the benefits for the mother.

Emicizumab (Hemlibra) Dose in Kidney disease:

In the manufacturer's labeling, no recommendations regarding dose adjustment has been provided. 

Emicizumab (Hemlibra) Dose in Liver disease:

In the manufacturer's labeling, no recommendations regarding dose adjustment has been provided. 

Common Side Effects of Emicizumab (Hemlibra):

• Central nervous system:

  • Headache

• Local:

  • Injection site reaction
  • Erythema at injection site

• Neuromuscular & skeletal:

  • Arthralgia

Less Common Side Effects of Emicizumab (Hemlibra):

• Dermatologic:

  • Injection site pruritus

• Gastrointestinal:

  • Diarrhea

• Immunologic:

  • Antibody development

• Local:

  • Pain at injection site

• Miscellaneous:

  • Fever

Contraindications to Emicizumab (Hemlibra):

There are no contraindications for its use, according to the manufacturer.

Warnings and precautions

• • Thromboembolism, Thrombotic microangiopathy: [US-Bound Warning]

    • Patients receiving emicizumab prophylaxis that are given activated prothrombin compound at a dose higher than 100 units/kg/24 hrs for >=24 hrs are at increased risk of developing thrombotic events or thrombotic microangiopathy.
    • Patients receiving a PCC should be closely monitored for thrombotic episodes and thrombotic microangiopathy.
    • Patients with symptoms of thrombotic conditions must stop taking a PCC.
    • Patients have presented with thrombocytopenia and microangiopathic hemolyticanemia in case-reports. However, there are no severe deficiencies in ADAMTS13 activation.
    • Patients with microangiopathy symptoms improved in one week, while patients who develop thromboembolism symptoms improved within a month after discontinuing the aPCC.
    • These symptoms should prompt the patient to stop taking a PCC and interrupt treatment.
    • When reinitiating treatment after symptoms have been resolved, it is important to weigh the benefits and risks of the treatment.

Emicizumab: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

  Risk Factor C (Monitor therapy).
  Complex Anti-inhibitor Coagulant (Human).	Emicizumab could increase the thrombogenic effects of Anti-inhibitor Coagulant Complex Human. Risk C: Monitor therapy
  Risk Factor X (Avoid Combination)
  Belimumab	Monoclonal Antibodies can increase the toxic/adverse effects of Belimumab.

Monitoring parameters:

Patients who are administeredby aPCC with Hemlibra injection should be monitored for thrombotic events and thrombotic microangiopathy. Coagulation parameters should be monitored while on treatment. Chromogenic or immune-based assays may be used to monitor the parameters of hemostasis.

Both human and bovine coagulation proteins may be used to monitor factor VIII activity via the Chromogenic assays. It is important to know that bovine assays are not very sensitive while human coagulation proteins factors assay may overestimate the hemostatic potential of the drug. The bovine coagulation factors assays can be used to monitor endogenous or infused FVIII activity or to measure anti-FVIII inhibitors.

A false negative result will be produced by the drug in clotting-based Bethesda assays for functional inhibition of FVIII, hence, a chromogenic Bethesda assay utilizing a bovine-based FVIII chromogenic test May be used that is insensitive to emicizumab. The effects of the drug on coagulation and hemostatic parameters may persist for as long as six months after the last administered dose because of its long half-life. 

How to administer Emicizumab (Hemlibra)?

It is administered as a subcutaneous injection. Do not shake the injection prior to administration. Administer the injection immediately following removal from the vial. The injection site should be rotated. The injection can be administered in the abdomen, thighs, or the upper outer arms.

Avoid injecting the drug into infected or inflamed areas, moles, scars, or skin that is tender, red, hard, and not intact. The patient can self inject the injection after proper education, however, only the healthcare provider may inject in the arms. Children who are younger than 7 years of age should not be allowed to self injection it.

When administering the dose, do not use different vials of different combinations.

Mechanism of action of Emicizumab (Hemlibra):

Emicizumab, a humanized monoclonal anti-human antibody, bridges the gap between factor IX (humanized monoclonal antibody), and factor IX (humanized polyclonal antibody). It is an IgG4 modified antibody (modified immunoglobulin G4) that restores function to factor VIII, but has no structural resemblance to factor VIII or sequence homology. It does not stimulate the production of inhibitors or antibodies against factor VIII. Bioavailability:

• SubQ: 80.4% to 93.1%

Half-life elimination:

• 26.9 ± 9.1 days

International Brand Names of Emicizumab:

• Hemlibra

Emicizumab Brand Names in Pakistan:

No Brands Available in Pakistan.