Emicizumab

Brand Names: Hemlibra

Drug Class: General Prescription

Overview

11 DESCRIPTION Emicizumab-kxwh is a humanized monoclonal modified immunoglobulin G4 (IgG4) bispecific antibody binding factor IXa and factor X. Emicizumab-kxwh has an approximate molecular weight of 145.6 kDa and is produced in genetically engineered mammalian (Chinese hamster ovary) cells.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action HEMLIBRA bridges activated factor IX and factor X to restore the function of missing activated factor VIII that is needed for effective hemostasis. 12.3 Pharmacokinetics Emicizumab-kxwh exhibited dose-proportional pharmacokinetics over a dose range of 0.3 mg/kg (0.1 times approved recommended starting dosage) to 6 mg/kg following subcutaneous administration. Following multiple subcutaneous administrations of a loading dose of 3 mg/kg emicizumab-kxwh once weekly for the first 4 weeks in hemophilia A patients, mean (± SD) trough plasma concentrations of 52.6 ± 13.6 μg/mL was achieved at Week 5. Sustained mean (± SD) plasma concentrations of emicizumab-kxwh at steady-state with the recommended maintenance doses are shown in Table 4 .

Indications

  • 1 INDICATIONS AND USAGE HEMLIBRA is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients ages newborn and older with hemophilia A (congenital factor VIII deficiency) with or without factor VIII inhibitors. HEMLIBRA is a bispecific factor IXa- and factor X-directed antibody indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients ages newborn and older with hemophilia A (congenital factor VIII deficiency) with or without factor VIII inhibitors. ( 1 )

Common Doses

  • 3 mg
  • 1.5 mg
  • 6 mg
  • 30 mg

Dosage

2 DOSAGE AND ADMINISTRATION Recommended loading dose is 3 mg/kg by subcutaneous injection once weekly for the first 4 weeks, followed by a maintenance dose of: 1.5 mg/kg once every week, or 3 mg/kg once every two weeks, or 6 mg/kg once every four weeks. ( 2.1 ) See Full Prescribing Information for important preparation and administration instructions. ( 2.2 ) 2.1 Recommended Dosage For subcutaneous use only. The recommended loading dose is 3 mg/kg by subcutaneous injection once weekly for the first 4 weeks, followed by a maintenance dose of: 1.

Black Box Warning

WARNING: THROMBOTIC MICROANGIOPATHY AND THROMBOEMBOLISM Cases of thrombotic microangiopathy and thrombotic events were reported when on average a cumulative amount of >100 U/kg/24 hours of activated prothrombin complex concentrate was administered for 24 hours or more to patients receiving HEMLIBRA prophylaxis. Monitor for the development of thrombotic microangiopathy and thrombotic events if aPCC is administered. Discontinue aPCC and suspend dosing of HEMLIBRA if symptoms occur.

Contraindications

  • 4 CONTRAINDICATIONS None. None ( 4 )

Side Effects

  • 6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Thrombotic Microangiopathy Associated with HEMLIBRA and aPCC [see Warnings and Precautions (5.1) ] Thromboembolism Associated with HEMLIBRA and aPCC [see Warnings and Precautions (5.2) ] Most common adverse reactions (incidence ≥ 10%) are injection site reactions, headache, and arthralgia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.

Interactions

  • 7 DRUG INTERACTIONS 7.1 Hypercoagulability with Concomitant Use of aPCC Clinical experience suggests that a drug interaction exists with HEMLIBRA and aPCC [see Warnings and Precautions (5.1 , 5.2) ] . 7.2 Drug-Laboratory Test Interactions HEMLIBRA restores the tenase cofactor activity of missing activated factor VIII (FVIIIa). Coagulation laboratory tests based on intrinsic clotting (i.e., aPTT) measure the total clotting time including time needed for activation of FVIII to FVIIIa by thrombin.