Emicizumab

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 )

• 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
• See Full Prescribing Information for important preparation and administration instructions
• 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: 1.5 mg/kg once every week, or 3 mg/kg once every two weeks, or 6 mg/kg once every four weeks
• The selection of a maintenance dose should be based on healthcare provider preference with consideration of regimens that may increase patient adherence
• Discontinue the prophylactic use of bypassing agents the day before starting HEMLIBRA prophylaxis
• The prophylactic use of factor VIII (FVIII) products may be continued during the first week of HEMLIBRA prophylaxis
• Missed Dose If a dose of HEMLIBRA is missed administer as soon as possible and then resume usual dosing schedule
• Do not administer two doses on the same day to make up for a missed dose
• Preparation and Administration HEMLIBRA is intended for use under the guidance of a healthcare provider
• After proper training in subcutaneous injection technique, a patient may self-inject, or the patient's caregiver may administer HEMLIBRA, if a healthcare provider determines that it is appropriate
• Self-administration is not recommended for children less than 7 years of age. …

HEMLIBRA is available as a colorless to slightly yellow solution in single-dose vials. Injection: 12 mg/0.4 mL 30 mg/mL 60 mg/0.4 mL 105 mg/0.7 mL 150 mg/mL 300 mg/2 mL (150 mg/mL) Injection: 12 mg/0.4 mL in a single-dose vial ( 3 ) 30 mg/mL in a single-dose vial ( 3 ) 60 mg/0.4 mL in a single-dose vial ( 3 ) 105 mg/0.7 mL in a single-dose vial ( 3 ) 150 mg/mL in a single-dose vial ( 3 ) 300 mg/2 …

• The safety and efficacy of HEMLIBRA have been established
• In pediatric patients
• Use of HEMLIBRA
• In pediatric patients with hemophilia A is supported by two randomized trials (HAVEN 1 and HAVEN 3) and two single-arm trials (HAVEN 2 and HAVEN 4)
• All clinical trials included
• Pediatric patients in the following age group: 47 adolescents (12 years up to less than 18 years)
• Only HAVEN 2 included
• Pediatric patients in the following age groups: 55 children (2 years up to less than 12 years) and five
• Infants (1 month up to less than 2 years). …

Clinical studies of HEMLIBRA did not include a sufficient number of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

• Advise the patient to read the FDA-approved patient labeling ( Medication Guide and Instructions for Use )
• Use of Bypassing Agents or FVIII Inform the patient and/or caregiver that HEMLIBRA increases coagulation potential
• Advise the patient and/or caregiver to discontinue prophylactic use of bypassing agents the day before starting HEMLIBRA prophylaxis
• Advise the patient and/or caregiver that prophylactic use of FVIII may be continued for the first week of HEMLIBRA prophylaxis. …

• None
• None

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. Such intrinsic pathway-based tests will yield overly shortened clotting times with HEMLIBRA, which does not require activation by thrombin. …

Immunogenicity: Anti-emicizumab antibodies (including neutralizing antibodies) have developed in HEMLIBRA-treated patients. In case of clinical signs of loss of efficacy, promptly assess the etiology and consider a change in treatment if neutralizing antibodies are suspected. ( 5.3 , 12.6 , 14.3 ) Laboratory Coagulation Test Interference: HEMLIBRA interferes with activated clotting time (ACT), activated partial thromboplastin time (aPTT), and coagulation laboratory tests based on aPTT, including one-stage aPTT-based single-factor assays, aPTT-based Activated Protein C Resistance (APC-R), and Bethesda assays (clotting-based) for factor VIII (FVIII) inhibitor titers. …

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. …

8.1 Pregnancy Risk Summary There are no available data on HEMLIBRA use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. Animal reproduction studies have not been conducted with emicizumab-kxwh. It is not known whether HEMLIBRA can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. …

Store HEMLIBRA vials in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Do not shake. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.