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Hemlibra

Generic Name: Emicizumab-kxwh
Class: Hemostatics

Medically reviewed on Dec 4, 2017

Warning

Warning: Thrombotic Microangiopathy and Thromboembolism1

See full prescribing information for complete boxed warning.1

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 (aPCC) was administered for 24 hours or more 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.1

Introduction

Emicizumab-kxwh is a hemostatic.

Uses for Hemlibra

Emicizumab-kxwh has the following uses:

Emicizumab-kxwh 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.1

Hemlibra Dosage and Administration

General

Emicizumab-kxwh is available in the following dosage form(s) and strength(s):

  • Injection: 30 mg/mL in a single-dose vial.1

  • Injection: 60 mg/0.4 mL in a single-dose vial.1

  • Injection: 105 mg/0.7 mL in a single-dose vial.1

  • Injection: 150 mg/mL in a single-dose vial.1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Recommended dose is 3 mg/kg by subcutaneous injection once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly.1

See Full Prescribing Information for important preparation and administration instructions.1

Cautions for Hemlibra

Contraindications

None.1

Warnings/Precautions

Thrombotic Microangiopathy Associated with Emicizumab-kxwh and aPCC

Cases of thrombotic microangiopathy (TMA) were reported from clinical trials when on average a cumulative amount of >100 U/kg/24 hours of activated prothrombin complex concentrate (aPCC) was administered for 24 hours or more to patients receiving emicizumab-kxwh prophylaxis. In clinical trials, thrombotic microangiopathy was reported in 1.6% of patients (3/189) and in 8.3% of patients (3/36) who received at least one dose of aPCC. Patients presented with thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury, without severe deficiencies in ADAMTS13 activity.1

Evidence of improvement was seen within one week following discontinuation of aPCC. One patient resumed emicizumab-kxwh following resolution of TMA.1

Consider the benefits and risks if aPCC must be used in a patient receiving emicizumab-kxwh prophylaxis. Monitor for the development of TMA when administering aPCC. Immediately discontinue aPCC and interrupt emicizumab-kxwh prophylaxis if clinical symptoms and/or laboratory findings consistent with TMA occur, and manage as clinically indicated. Consider the benefits and risks of resuming emicizumab-kxwh prophylaxis following complete resolution of TMA on a case-by-case basis.1

Thromboembolism Associated with Emicizumab-kxwh and aPCC

Thrombotic events were reported from clinical trials when on average a cumulative amount of >100 U/kg/24 hours of aPCC was administered for 24 hours or more to patients receiving emicizumab-kxwh prophylaxis. In clinical trials, thrombotic events were reported in 1.1% of patients (2/189) and in 5.6% of patients (2/36) who received at least one dose of aPCC.1

No thrombotic event required anticoagulation therapy. Evidence of improvement or resolution was seen within one month following discontinuation of aPCC. One patient resumed emicizumab-kxwh following resolution of thrombotic event.1

Consider the benefits and risks if aPCC must be used in a patient receiving emicizumab-kxwh prophylaxis. Monitor for the development of thromboembolism when administering aPCC. Immediately discontinue aPCC and interrupt emicizumab-kxwh prophylaxis if clinical symptoms, imaging, or laboratory findings consistent with thromboembolism occur, and manage as clinically indicated. Consider the benefits and risks of resuming emicizumab-kxwh prophylaxis following complete resolution of thrombotic events on a case-by-case basis.1

Laboratory Coagulation Test Interference

Emicizumab-kxwh 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. Therefore, intrinsic pathway clotting-based laboratory test results in patients treated with emicizumab-kxwh should not be used to monitor emicizumab-kxwh activity, determine dosing for factor replacement or anti-coagulation, or measure FVIII inhibitor titers. Laboratory tests affected and unaffected by emicizumab-kxwh are shown in Table 1.1

Table 1. Coagulation Test Results Affected and Unaffected by Emicizumab-kxwh

Results Affected by Emicizumab-kxwh

Results Unaffected by Emicizumab-kxwh

Activated partial thromboplastin time (aPTT)

Bethesda assays (clotting-based) for FVIII inhibitor titers

One-stage, aPTT-based, single-factor assays

aPTT-based Activated Protein C Resistance (APC-R)

Activated clotting time (ACT)

Bethesda assays (bovine chromogenic) for FVIII inhibitor titers

Thrombin time (TT)

One-stage, prothrombin time (PT)-based, single-factor assays

Chromogenic-based single-factor assays other than FVIII

Immuno-based assays (i.e., ELISA, turbidimetric methods)

Genetic tests of coagulation factors (e.g., Factor V Leiden, Prothrombin 20210)

Specific Populations

Pregnancy

Risk Summary: There are no available data on emicizumab-kxwh 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 emicizumab-kxwh can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Emicizumab-kxwh should be used during pregnancy only if the potential benefit for the mother outweighs the risk to the fetus.1

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 2–4% and 15–20%, respectively.1

Lactation

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 emicizumab-kxwh and any potential adverse effects on the breastfed child from emicizumab-kxwh or from the underlying maternal condition.1

Females And Males of Reproductive Potential

Women of childbearing potential should use contraception while receiving emicizumab-kxwh.1

Pediatric Use

The safety and efficacy of emicizumab-kxwh have been established in pediatric patients. Use of emicizumab-kxwh 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.1

In general, the adverse reactions in emicizumab-kxwh-treated pediatric patients were similar in type to those seen in adult patients with hemophilia A with FVIII inhibitors.1

The steady-state plasma trough concentrations of emicizumab-kxwh were comparable in adult and pediatric patients at equivalent weight-based doses.1

Geriatric Use

Clinical studies of emicizumab-kxwh did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.1

Common Adverse Effects

Most common adverse reactions (incidence ≥10%) are injection site reactions, headache, and arthralgia.1

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Emicizumab-kxwh bridges activated factor IX and factor X to restore the function of missing activated factor VIII that is needed for effective hemostasis.1

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).1

Use of Bypassing Agents

Inform the patient and/or caregiver that emicizumab-kxwh increases coagulation potential. Advise the patient and/or caregiver to discontinue prophylactic use of bypassing agents the day before starting emicizumab-kxwh prophylaxis. Discuss the use of bypassing agents with the patient and/or caregiver prior to starting emicizumab-kxwh prophylaxis.1

Thrombotic Microangiopathy Associated with Emicizumab-kxwh and aPCC

Inform the patient and/or caregiver of the potential risk of thrombotic microangiopathy if aPCC is administered while receiving emicizumab-kxwh 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.1

Thromboembolism Associated with Emicizumab-kxwh and aPCC

Inform the patient and/or caregiver of the potential risk of thromboembolism if aPCC is administered while receiving emicizumab-kxwh 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.1

Laboratory Coagulation Test Interference

Inform the patient and/or caregiver that emicizumab-kxwh 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.1

Instruction on Injection Technique

Emicizumab-kxwh is intended for use under the guidance of a healthcare provider. If a patient or caregiver is to administer subcutaneous emicizumab-kxwh, instruct him/her in injection techniques and assess his/her ability to inject subcutaneously to ensure proper administration of subcutaneous emicizumab-kxwh and the suitability for home use.1

Advise the patient to follow the recommendations in the FDA-approved patient labeling regarding proper sharps disposal.1

Additional Information

AHFS First Release. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Emicizumab-kxwh

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, Solution

30 mg /1 mL

Hemlibra

Genentech Inc.

150 mg /1 mL

Hemlibra

Genentech Inc.

AHFS Drug Information. © Copyright 2018, Selected Revisions December 4, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Genentech, Inc.. Hemlibra (emicizumab-kxwh) SUBCUTANEOUS prescribing information. 2017 Nov. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2483adba-fab6-4d1b-96c5-c195577ed071

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