Emicizumab

B02B - Vitamin K and other haemostatics ATC B02BX06 Antibody approved 2017 Parenteral First-in-class Black-box warning

JFDA label: Hemlibra solution for injection 30mg/1ml

⚠ Black-Box Warning

Thrombotic microangiopathy and thromboembolism:

Mechanism of Action

Other of Coagulation factor IX and X — Coagulation factor IX and X other

Target	Action	Gene / class
Coagulation factor IX and X efficacy	OTHER

Indications

Approved

Hemophilia A, prophylaxis

Contraindications

Source: Lexicomp

There are no contraindications listed in the manufacturer's labeling Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (1)

Very Common Headache

Immune system disorders (1)

Very Common Antibody development

Gastrointestinal disorders (1)

Common Diarrhea

Skin and subcutaneous tissue disorders (1)

Common Injection site pruritus

Musculoskeletal and connective tissue disorders (2)

Common Arthralgia · myalgia

General disorders and administration site conditions (4)

Very Common Injection site reaction

Common Erythema at injection site · Fever · pain at injection site

Dosing

Source: Lexicomp

Hemophilia A, prophylaxis: SubQ: Initial: 3 mg/kg once weekly for 4 weeks, then 1.5 mg/kg once weekly thereafter

Hemophilia A, prophylaxis: Infants, Children, and Adolescents: SubQ: Initial: Refer to adult dosing.

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer's labeling.

Warnings & Precautions

Source: Lexicomp

Thrombotic microangiopathy and thromboembolism

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 (aPPC) concentrate was administered for ≥24 hours to patients receiving emicizumab-kxwh prophylaxis. Monitor for the development of thrombotic microangiopathy and thrombotic events if aPCC is administered. Discontinue aPCC and suspend dosing of emicizumab-kxwh 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-kxwh; consider benefits vs risks of resuming emicizumab-kxwh 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.

Pregnancy & Lactation

Pregnancy

Animal reproduction studies have not been conducted. Emicizumab-kxwh is a humanized monoclonal immunoglobulin; endogenous IgG crosses the placenta. Females of childbearing potential should use effective contraception during therapy.

Lactation

It is not known if emicizumab-kxwh is present in breast milk. However, emicizumab-kxwh is a humanized monoclonal immunoglobulin; endogenous IgG is present in breast milk. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Monitoring

Clinical pearl	Monitor for thrombotic microangiopathy and thrombotic events if aPCC is administered with emicizumab-kxwh. 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-kxwh; however, bovine coagulation factors assays are insensitive to emicizumab-kxwh (no activity measured) and can be used to monitor endogenous or infused FVIII activity, or to measure anti-FVIII inhibitors. Emicizumab-kxwh 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-kxwh may be used. Due to the long half-life of emicizumab-kxwh, effects on coagulation assays may persist ≤6 months after the last dose.

Clinical pearl

Monitor for thrombotic microangiopathy and thrombotic events if aPCC is administered with emicizumab-kxwh. 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-kxwh; however, bovine coagulation factors assays are insensitive to emicizumab-kxwh (no activity measured) and can be used to monitor endogenous or infused FVIII activity, or to measure anti-FVIII inhibitors. Emicizumab-kxwh 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-kxwh may be used. Due to the long half-life of emicizumab-kxwh, effects on coagulation assays may persist ≤6 months after the last dose.

Biology & Pharmacokinetics

Pharmacokinetics

Bioavailability	80.4%
Half-life	27.8 ± 8.1 days

Drug–drug interactions (3, DDInter)

Interacting drug	Severity	Management
Anti-inhibitor coagulant complex	major
Antihemophilic factor, human recombinant	moderate
Coagulation factor VIIa Recombinant Human	moderate

Registered Products (4)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Hemlibra solution for injection	Injection 30 mg/1 ml	1 vial	Shawi & Rushedat Drug Store	—
Hemlibra solution for injection	Injection 150 mg/1 ml	1 vial	Shawi & Rushedat Drug Store	—
Hemlibra solution for injection 105mg/0.7ml	Injection 105 mg/0.7 ml	1 vial	Shawi & Rushedat Drug Store	—
Hemlibra solution for injection 60mg/0.4ml	Injection 60 mg/0.4 ml	1 vial	Shawi & Rushedat Drug Store	—