Drug Interaction:
DRUG INTERACTIONS
Hypercoagulability with Concomitant Use of aPCC, rFVIIa, or FVIII Clinical experience suggests that a drug interaction exists with HEMLIBRA and aPCC .
There is a possibility for hypercoagulability with rFVIIa or FVIII with HEMLIBRA based on preclinical experiments
Indication:
U.S. FDA APPROVED DRUGS DURING 2017
Sr.No- 40
Name of the Drug- Hemlibra
Active Ingredient- Emicizumab
Pharmacological Classification-
To prevent or reduce the frequency of bleeding episodes in adult
and pediatric patients with hemophilia A who have developed
antibodies called Factor VII (FVIII) inhibiors
Date of Approval- 11-16-2017
(Ref- FDA approved List 2017)
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
HEMLIBRA safely and effectively. See full prescribing information for HEMLIBRA.
HEMLIBRA® (emicizumab-kxwh) injection, for subcutaneous use
Initial U.S. Approval: 2017
INDICATIONS AND USAGE-
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 with hemophilia A (congenital factor VIII deficiency) with factor VIII inhibitors.
DOSAGE AND ADMINISTRATION-
Recommended dose is 3 mg/kg by subcutaneous injection once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly.
Adverse Reaction:
ADVERSE REACTIONS-
Most common adverse reactions (incidence 10%) are injection site reactions, headache, and arthralgia.
Contra-Indications:
CONTRAINDICATIONS-
None
WARNINGS AND PRECAUTIONS
Laboratory Coagulation Test Interference:
HEMLIBRA interferes with activated clotting time (ACT), activated partial thromboplastin time (aPTT), and coagulation laboratory tests based on aPTT, including onestage aPTT-based single-factor assays, aPTT-based Activated Protein C Resistance (APC-R), and Bethesda assays (clotting-based) for factor VIII (FVIII) inhibitor titers. Intrinsic pathway clotting-based laboratory tests should not be used.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE-
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 with hemophilia A (congenital factor VIII deficiency) with factor VIII inhibitors.
DOSAGE AND ADMINISTRATION-
Recommended dose is 3 mg/kg by subcutaneous injection once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly.
DOSAGE FORMS AND STRENGTHS-
Injection: 30 mg/mL in a single-dose vial
60 mg/0.4 mL in a single-dose vial
105 mg/0.7 mL in a single-dose vial
150 mg/mL in a single-dose vial
Patient Information:
PATIENT COUNSELING INFORMATION-
Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).
Use of Bypassing Agents
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.
Discuss the use of bypassing agents with the patient and/or caregiver prior to starting HEMLIBRA prophylaxis [see Adverse Reactions (6.1)].
Thrombotic Microangiopathy Associated with HEMLIBRA and aPCC
Inform the patient and/or caregiver of the potential risk of thrombotic microangiopathy if aPCC is administered while receiving HEMLIBRA prophylaxis.
Instruct the patient and/or caregiver to consult their healthcare provider if aPCC is required in cumulative doses exceeding 100 U/kg.
Advise the patient and/or caregiver to seek immediate medical attention if any signs or symptoms of thrombotic microangiopathy occur [see Warnings and Precautions (5.1)].
Thromboembolism Associated with HEMLIBRA and aPCC
Inform the patient and/or caregiver of the potential risk of thromboembolism if aPCC is administered while receiving HEMLIBRA prophylaxis.
Instruct the patient and/or caregiver to consult their healthcare provider if aPCC is required in cumulative doses exceeding 100 U/kg.
Advise the patient and/or caregiver to seek immediate medical attention if any signs or symptoms of thromboembolism occur [see Warnings and Precautions (5.2)].
Laboratory Coagulation Test Interference
Inform the patient and/or caregiver that HEMLIBRA interferes with some laboratory tests that measure blood clotting and may cause a false reading.
Advise the patient and/or caregiver that they should notify any healthcare provider about this possibility prior to any blood tests or medical procedures [see Warnings and Precautions (5.3)].
Instruction on Injection Technique
HEMLIBRA is intended for use under the guidance of a healthcare provider.
If a patient or caregiver is to administer subcutaneous HEMLIBRA, instruct him/her in injection techniques and assess his/her ability to inject subcutaneously to ensure proper administration of subcutaneous HEMLIBRA and the suitability for home use [see Instructions for Use].
Advise the patient to follow the recommendations in the FDA-approved patient labeling regarding proper sharps disposal.
HEMLIBRA® [emicizumab-kxwh] Manufactured by:
Genentech, Inc. A Member of the Roche Group 1 DNA Way South San Francisco, CA 94080-4990 U.S. License No. 1048
HEMLIBRA® is a registered trademark of Chugai Pharmaceutical Co., Ltd., Tokyo, Japan ©2017 Genentech, Inc. All rights reserved.
Medication Guide HEMLIBRA® (hem-lee-bruh) (emicizumab-kxwh) injection, for subcutaneous use
Pharmacology/ Pharmacokinetics:
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 3 mg/kg once weekly following subcutaneous administration.
Following multiple subcutaneous administrations of 3 mg/kg once weekly for the first 4 weeks in hemophilia A patients, mean (± SD) trough plasma concentrations of emicizumab-kxwh increased to achieve 54.6 ± 14.3 µg/mL at Week 5.
Trough plasma concentrations above 50 µg/mL were sustained thereafter with the recommended weekly dosage of 1.5 mg/kg; the mean (± SD) trough plasma concentrations of emicizumab-kxwh at steadystate was 52.8 ? 13.5 µg/mL.
Absorption
Following subcutaneous administration, the mean (± SD) absorption half-life was 1.7 ? 1 day. The absolute bioavailability following subcutaneous administration of 1 mg/kg was between 80.4% and 93.1%.
Similar pharmacokinetic profiles were observed following subcutaneous administration in the abdomen, upper arm, and thigh [see Dosage and Administration (2.2)].
Distribution
The mean apparent volume of distribution was 11.4 L (95% confidence interval (CI) [10.6, 12.1]).
Elimination The mean apparent clearance (95% CI) was 0.24 L/day (0.22, 0.26) and the mean elimination apparent half-life (± SD) was 27.8 ? 8.1 days.
Specific Populations
The pharmacokinetics of emicizumab-kxwh are not influenced by age (3 years to 75 years), race (White 54%, Asian 30.5% and Black 8.5%), inhibitor status (inhibitor present, 92%), mild hepatic impairment (defined as total bilirubin 1x to ??1.5x the upper limit of normal (ULN) and any aspartate transaminase (AST) level) and moderate hepatic impairment (defined as total bilirubin 1.5x to ??3x the ULN and any AST level).
Body weight: The apparent clearance and volume of distribution of emicizumab-kxwh increased with increasing body weight (14.2 kg to 131 kg). Dosing in mg/kg provides similar emicizumabkxwh exposure across body weight range.
Drug Interaction Studies No drug-drug interaction studies have been conducted with HEMLIBRA.
13 NONCLINICAL TOXICOLOGY 13
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
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.
HEMLIBRA should be used during pregnancy only if the potential benefit for the mother outweighs the risk to the fetus.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
2. Lactation Risk Summary-
There is no information regarding the presence of emicizumab-kxwh in human milk, the effects on the breastfed child, or the effects on milk production. Human IgG is known to be present in human milk.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for HEMLIBRA and any potential adverse effects on the breastfed child from HEMLIBRA or from the underlying maternal condition.
8.3 Females and Males of Reproductive Potential Contraception-
Women of childbearing potential should use contraception while receiving HEMLIBRA.
8.4 Pediatric Use
The safety and efficacy of HEMLIBRA have been established in pediatric patients. Use of HEMLIBRA in pediatric patients with hemophilia A with FVIII inhibitors is supported by a randomized trial (HAVEN 1) and a single-arm trial (HAVEN 2).
HAVEN 1 included pediatric patients in the following age group: 38 adolescents (12 years to less than 18 years).
HAVEN 2 included pediatric patients in the following age groups: 55 children (2 years up to less than 12 years) and two infants (1 month up to less than 2 years). No differences in efficacy were observed between the different age groups [see Clinical Studies (14)].
In general, the adverse reactions in HEMLIBRA-treated pediatric patients were similar in type to those seen in adult patients with hemophilia A with FVIII inhibitors [see Adverse Reactions (6.1)].
The steady-state plasma trough concentrations of emicizumab-kxwh were comparable in adult and pediatric patients at equivalent weight-based doses [see Clinical Pharmacology (12.3)].
8.5 Geriatric Use
Clinical studies of HEMLIBRA did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. 11
