Emicizumab

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous [preservative free]:

Hemlibra: emicizumab-kxwh 30 mg/1 mL (1 mL); emicizumab-kxwh 150 mg/1 mL (1 mL); emicizumab-kxwh 60 mg/0.4 mL (0.4 mL); emicizumab-kxwh 105 mg/0.7 mL (0.7 mL)

Pharmacology

Mechanism of Action

Emicizumab, a humanized monoclonal modified immunoglobulin G4 (IgG4) antibody with a bispecific factor IXa- and factor X-directed antibody, bridges activated factor IX and factor X to restore the function of missing activated factor VIII that is needed for effective hemostasis. Emicizumab has no structural relationship or sequence homology to FVIII and, therefore, does not induce or enhance the development of direct inhibitors to FVIII.

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: 10.4 L

Half-Life Elimination

26.9 ± 9.1 days

Use in Specific Populations

Special Populations Note

Body weight: Clearance and volume of distribution increase with increasing body weight (9 kg to 156 kg). Dosing in mg/kg provides similar emicizumab exposure across body weight range.

Use: Labeled Indications

Hemophilia A, prophylaxis: Routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A (congenital factor VIII deficiency) with or without factor VIII inhibitors

Contraindications

There are no contraindications listed in the US manufacturer's labeling.

Canadian labeling: Hypersensitivity to emicizumab or any component of the formulation.

Dosage and Administration

Dosing: Adult

Hemophilia A, prophylaxis: SubQ:

Initial: 3 mg/kg once weekly for 4 weeks

Maintenance: 1.5 mg/kg once weekly or 3 mg/kg once every 2 weeks or 6 mg/kg once every 4 weeks

Note: Prophylactic use of bypassing agents should be discontinued the day before starting therapy. Prophylactic use of FVIII may be continued during the first week of therapy.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Hemophilia A, prophylaxis: Note: Prophylactic use of bypassing agents should be discontinued the day before starting therapy. Prophylactic use of FVIII may be continued during the first week of therapy.

Infants, Children, and Adolescents:

Initial loading dose: SubQ: 3 mg/kg once weekly for first 4 weeks (4 doses)

Maintenance therapy: Note: Multiple regimens available, and selection should be based on health care provider preferences and increased patient adherence. SubQ: 1.5 mg/kg once weekly or 3 mg/kg once every 2 weeks or 6 mg/kg once every 4 weeks

Administration

SubQ: For SubQ administration. Do not shake. Administer immediately after removal from vial. Rotate injection sites (upper outer arms, thighs, or any quadrant of abdomen). Do not inject into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact. Patient may self-inject, or the patient's caregiver may administer; however, only a health care provider should administer in the upper outer arm. Self-administration is not recommended for children <7 years of age.

Refer to product information for preparation and additional administration techniques. Do not use different vials of different concentrations when combining vials to administer prescribed dose.

Storage

Store at 2°C to 8°C (36°F to 46°F); protect from light. Do not freeze. May also store unopened vials at <30°C (<86°F) for up to 7 days. Once removed from the vial, discard if not used immediately. Discard unused solution.

Drug Interactions

Anti-inhibitor Coagulant Complex (Human): Emicizumab may enhance the thrombogenic effect of Anti-inhibitor Coagulant Complex (Human). Monitor therapy

Test Interactions

Emicizumab affects intrinsic pathway clotting-based laboratory tests, including activated clotting time (ACT), activated partial thromboplastin time (aPTT), and all assays based on aPTT, such as one-stage factor VIII (FVIII) activity. Do not use intrinsic pathway clotting based laboratory test results to monitor emicizumab.

Adverse Reactions

>10%:

Central nervous system: Headache (15%)

Local: Injection site reaction (22%), erythema at injection site (11%)

Neuromuscular & skeletal: Arthralgia (15%)

1% to 10%:

Dermatologic: Injection site pruritus (4%)

Gastrointestinal: Diarrhea (6%)

Immunologic: Antibody development (4%; neutralizing: <1%)

Local: Pain at injection site (4%)

Miscellaneous: Fever (6%)

<1%, postmarketing, and/or case reports: Rhabdomyolysis

Warnings/Precautions

Concerns related to adverse effects:

• Thrombotic microangiopathy and thromboembolism: [US Boxed Warning]: Cases of thrombotic microangiopathy and thrombotic events were reported when on average a cumulative amount of >100 units/kg/24 hours of activated prothrombin complex concentrate (aPCC) was administered for ≥24 hours to patients receiving emicizumab prophylaxis. Monitor for the development of thrombotic microangiopathy and thrombotic events if aPCC is administered. Discontinue aPCC and suspend dosing of emicizumab if symptoms occur. Patients presented with thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury, without severe deficiencies in ADAMTS13 activity; improvement of thrombotic microangiopathy and thromboembolism was seen within 1 week and 1 month, respectively, following discontinuation of aPCC. If these complications occur, discontinue aPCC immediately and interrupt emicizumab; consider benefits vs risks of resuming emicizumab following complete resolution of thrombotic microangiopathy and thrombotic events.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Monitoring Parameters

Monitor for thrombotic microangiopathy and thrombotic events if aPCC is administered with emicizumab.

Monitor coagulation parameters using single factor assays utilizing chromogenic or immuno-based methods. Chromogenic FVIII activity tests may be manufactured with either human or bovine coagulation proteins; human coagulation factors assays may overestimate the clinical hemostatic potential of emicizumab; however, bovine coagulation factors assays are insensitive to emicizumab (no activity measured) and can be used to monitor endogenous or infused FVIII activity, or to measure anti-FVIII inhibitors. Emicizumab will produce a false negative result in clotting-based Bethesda assays for functional inhibition of FVIII; a chromogenic Bethesda assay utilizing a bovine-based FVIII chromogenic test that is insensitive to emicizumab may be used. Due to the long half-life of emicizumab, effects on coagulation assays may persist ≤6 months after the last dose.

Pregnancy

Pregnancy Considerations

Animal reproduction studies have not been conducted. Emicizumab is a humanized monoclonal antibody (IgG₄). Potential placental transfer of human IgG is dependent upon the IgG subclass and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).

Females of childbearing potential should use effective contraception during therapy.

Patient Education

What is this drug used for?

• It is used to prevent bleeding in people with hemophilia A.

Frequently reported side effects of this drug

• Muscle pain
• Joint pain
• Diarrhea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Blood clots like numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; chest pain; shortness of breath; fast heartbeat; or coughing up blood.
• Confusion
• Passing out
• Weakness
• Back pain
• Abdominal pain
• Vision changes
• Chest pain
• Coughing up blood
• Eye pain
• Eye swelling
• Fast heartbeat
• Facial numbness
• Extremity pain
• Shortness of breath
• Swelling of the arms or legs
• Trouble urinating
• Nausea
• Vomiting
• Severe headache
• Yellow skin
• Severe injection site irritation
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.