Enter drug's generic or brand name below. Results will appear here. Note: all drug related information obtained on this page is provided by RX List.
Using the RX LIST database:
(1) Enter the drug name in the search box below and hit ENTER
(2) The rx list web site will open here with the drug search completed. Next, scroll down the page to locate the link to the drug you are searching for and then click on the link.
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.
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. Emicizumab-kxwh has no structural relationship or sequence homology to FVIII and, as such, does not induce or enhance the development of direct inhibitors to FVIII.
HEMLIBRA (emicizumab-kxwh) injection is a sterile, preservative-free, colorless to slightly yellow solution for subcutaneous injection supplied in single-dose vials containing emicizumabkxwh at 30 mg/mL, 60 mg/0.4 mL, 105 mg/0.7 mL, or 150 mg/mL.
Each single-dose 30 mg vial contains a 1 mL solution of emicizumab-kxwh (30 mg), L-arginine (26.1 mg), L-histidine (3.1 mg), and poloxamer 188 (0.5 mg), adjusted to pH 6.0 with L-aspartic acid.
Each single-dose 60 mg vial contains a 0.4 mL solution of emicizumab-kxwh (60 mg), L-arginine (10.5 mg), L-histidine (1.2 mg), and poloxamer 188 (0.2 mg), adjusted to pH 6.0 with L-aspartic acid.
Each single-dose 105 mg vial contains a 0.7 mL solution of emicizumab-kxwh (105 mg), L-arginine (18.3 mg), L-histidine (2.2 mg), and poloxamer 188 (0.4 mg), adjusted to pH 6.0 with L-aspartic acid.
Each single-dose 150 mg vial contains a 1 mL solution of emicizumab-kxwh (150 mg), L-arginine (26.1 mg), L-histidine (3.1 mg), and poloxamer 188 (0.5 mg), adjusted to pH 6.0 with L-aspartic acid.
The following serious adverse reactions are described elsewhere in the labeling:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The following adverse reactions are based on pooled data from two randomized trials in adult and adolescent patients (HAVEN 1 and HAVEN 3), one single-arm trial in adult and adolescent patients (HAVEN 4), one single-arm trial in pediatric patients (HAVEN 2), and one dose-finding trial, in which a total of 391 male patients with hemophilia A received at least one dose of HEMLIBRA as routine prophylaxis. Two hundred eighty-one patients (72%) were adults (18 years and older), 50 (13%) were adolescents (12 years up to less than 18 years), 55 (14%) were children (2 years up to less than 12 years), and five (1%) were infants (1 month up to less than 2 years). The median duration of exposure across the studies was 34.1 weeks (0.1 to 224.4 weeks).
The most frequently reported adverse reactions observed in ≥ 10% of patients treated with HEMLIBRA were injection site reactions, headache, and arthralgia.
Four patients (1%) in the clinical trials receiving HEMLIBRA prophylaxis withdrew from treatment due to adverse reactions, which were thrombotic microangiopathy, skin necrosis and superficial thrombophlebitis, headache, and injection site reaction.
Adverse reactions observed in patients who received HEMLIBRA are shown in Table 2.
Table 2 Adverse Reactions Reported in ≥ 5% of Patients from Pooled Clinical Trials with HEMLIBRA
|
Body System |
Adverse Reaction |
Number of Patients |
|
General Disorders and Administration Site Conditions |
Injection site reaction* |
85 (22%) |
|
Pyrexia |
23 (6%) |
|
|
Nervous System Disorders |
Headache |
57 (15%) |
|
Gastrointestinal Disorders |
Diarrhea |
22 (6%) |
|
Musculoskeletal and Connective Tissue Disorders |
Arthralgia |
59 (15%) |
| * Includes injection site bruising, injection site discomfort, injection site erythema, injection site hematoma, injection site induration, injection site pain, injection site pruritus, injection site rash, injection site reaction, injection site swelling, injection site urticaria, and injection site warmth.. | ||
Characterization of aPCC treatment in pooled clinical trials
There were 130 instances of aPCC treatment in 37 patients, of which 13 instances (10%) consisted of on average a cumulative amount of >100 U/kg/24 hours of aPCC for 24 hours or more; two of the 13 were associated with thrombotic events and three of the 13 were associated with TMA (Table 3). No TMA or thrombotic events were associated with the remaining instances of aPCC treatment.
Table 3 Characterization of aPCC Treatment* in Pooled Clinical Trials
|
Duration of aPCC treatment |
Average cumulative amount of aPCC over 24 hours (U/kg/24 hours) |
||
|
< 50 |
50 – 100 |
> 100 |
|
|
< 24 hours |
11 |
76 |
18 |
|
24 – 48 hours |
0 |
6 |
3a |
|
> 48 hours |
1 |
5 |
10a,b,b,b |
| * An instance of aPCC treatment is defined as all doses of aPCC received by a patient, for any reason, until there was a 36-hour treatment-free break. a Thrombotic event. bThrombotic microangiopathy. |
|||
Injection Site Reactions
In total, 85 patients (22%) reported injection site reactions (ISRs). All ISRs observed in HEMLIBRA clinical trials were reported as mild to moderate intensity and 93% resolved without treatment. The commonly reported ISR symptoms were injection site erythema (11%), injection site pain (4%), and injection site pruritus (4%).
Other Less Common (<1%) Reactions
Rhabdomyolysis was reported in two adult patients with asymptomatic elevations in serum creatine kinase without associated renal or musculoskeletal symptoms. In both instances, the event occurred following an increase in physical activity.
The following adverse reactions have been identified during post-approval use of HEMLIBRA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Skin and subcutaneous tissue disorders: rash, urticaria, angioedema.
Immune system disorders: hypersensitivity.
Clinical experience suggests that a drug interaction exists with HEMLIBRA and aPCC [see Warnings and Precautions (5.1, 5.2)].
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. The overly shortened intrinsic clotting time will then disturb all single-factor assays based on aPTT, such as the one-stage FVIII activity assay; however, singlefactor assays utilizing chromogenic or immuno-based methods are unaffected by HEMLIBRA and may be used to monitor coagulation parameters during treatment, with specific considerations for FVIII chromogenic activity assays as described below.
Chromogenic FVIII activity tests may be manufactured with either human or bovine coagulation proteins. Assays containing human coagulation factors are responsive to HEMLIBRA but may overestimate the clinical hemostatic potential of HEMLIBRA. In contrast, assays containing bovine coagulation factors are insensitive to HEMLIBRA (no activity measured) and can be used to monitor endogenous or infused FVIII activity, or to measure anti-FVIII inhibitors.
HEMLIBRA remains active in the presence of inhibitors against FVIII, so it will produce a falsenegative result in clotting-based Bethesda assays for functional inhibition of FVIII. Instead, a chromogenic Bethesda assay utilizing a bovine-based FVIII chromogenic test that is insensitive to HEMLIBRA may be used.
Due to the long half-life of HEMLIBRA, effects on coagulation assays may persist for up to 6 months after the last dose [see Clinical Pharmacology (12.3)].
Included as part of the PRECAUTIONS section.
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 HEMLIBRA prophylaxis. In clinical trials, thrombotic microangiopathy was reported in 0.8% of patients (3/391) and in 8.1% of patients (3/37) 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.
Evidence of improvement was seen within one week following discontinuation of aPCC. One patient resumed HEMLIBRA following resolution of TMA.
Consider the benefits and risks if aPCC must be used in a patient receiving HEMLIBRA prophylaxis. Due to the long half-life of HEMLIBRA, the potential for an interaction with aPCC may persist for up to 6 months after the last dose. Monitor for the development of TMA when administering aPCC. Immediately discontinue aPCC and interrupt HEMLIBRA prophylaxis if clinical symptoms and/or laboratory findings consistent with TMA occur, and manage as clinically indicated. Consider the benefits and risks of resuming HEMLIBRA prophylaxis following complete resolution of TMA on a case-by-case basis.
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 HEMLIBRA prophylaxis. In clinical trials, thrombotic events were reported in 0.5% of patients (2/391) and in 5.4% of patients (2/37) who received at least one dose of aPCC.
No thrombotic event required anticoagulation therapy. Evidence of improvement or resolution was seen within one month following discontinuation of aPCC. One patient resumed HEMLIBRA following resolution of thrombotic event.
Consider the benefits and risks if aPCC must be used in a patient receiving HEMLIBRA prophylaxis. Due to the long half-life of HEMLIBRA, the potential for an interaction with aPCC may persist for up to 6 months after the last dose. Monitor for the development of thromboembolism when administering aPCC. Immediately discontinue aPCC and interrupt HEMLIBRA prophylaxis if clinical symptoms, imaging, or laboratory findings consistent with thromboembolism occur, and manage as clinically indicated. Consider the benefits and risks of resuming HEMLIBRA prophylaxis following complete resolution of thrombotic events on a case-by-case basis.
Treatment with HEMLIBRA may induce anti-drug antibodies. Anti-emicizumab-kxwh antibodies were reported in 5.1% of patients (34/668) treated with HEMLIBRA in clinical trials. Most patients with anti-emicizumab-kxwh antibodies did not experience a change in HEMLIBRA plasma concentrations or an increase in bleeding events; however, in uncommon cases (incidence < 1%), the presence of neutralizing antibodies with decreasing plasma concentration may be associated with loss of efficacy [see Clinical Pharmacology (12.6), Clinical Studies (14.3)].
Monitor for clinical signs of loss of efficacy (e.g., increase in breakthrough bleeding events) and if observed, promptly assess the etiology and consider a change in treatment if neutralizing antiemicizumab-kxwh antibodies are suspected.
HEMLIBRA 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 (Table 1). Therefore, intrinsic pathway clottingbased laboratory test results in patients treated with HEMLIBRA should not be used to monitor HEMLIBRA activity, determine dosing for factor replacement or anti-coagulation, or measure FVIII inhibitor titers [see Drug Interactions (7.2)]. Laboratory tests affected and unaffected by HEMLIBRA are shown in Table 1.
Table 1 Coagulation Test Results Affected and Unaffected by HEMLIBRA
|
Results Affected by HEMLIBRA |
Results Unaffected by HEMLIBRA |
|
Activated partial thromboplastin time (aPTT) |
Bethesda assays (bovine chromogenic) for FVIII inhibitor titers |
| *For important considerations regarding FVIII chromogenic activity assays, see Drug Interactions (7.2). | |
Studies in animals investigating the carcinogenic effects of emicizumab-kxwh have not been conducted. In vitro and in vivo testing of emicizumab-kxwh for genotoxicity was not conducted.
Animal fertility studies have not been conducted; however, emicizumab-kxwh did not cause any toxicological changes in the reproductive organs of male or female cynomolgus monkeys at doses of up to 30 mg/kg/week in subcutaneous general toxicity studies of up to 26-week duration and at doses of up to 100 mg/kg/week in a 4-week intravenous general toxicity study.
Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).
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. Discuss the appropriate dosing of concomitant agents such as bypassing agents or FVIII with the patient and/or caregiver prior to starting HEMLIBRA prophylaxis [see Warnings and Precautions (5.1, 5.2) and Drug Interactions (7.1)].
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)].
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)].
Inform the patient and/or caregiver of the uncommon occurrence (incidence < 1%) of loss of efficacy while receiving HEMLIBRA prophylaxis due to immunogenicity (neutralizing antiemicizumab-kxwh antibodies). Instruct the patient and/or caregiver to promptly report clinical signs of loss of efficacy (e.g., increase in breakthrough bleeding events) [see Warnings and Precautions (5.3)].
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 (5.4)].
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.
No information provided
No information provided
HEMLIBRA bridges activated factor IX and factor X to restore the function of missing activated factor VIII that is needed for effective hemostasis.
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.
Table 4 Mean (± SD) Steady-State Concentrations after emicizumab-kxwh Loading Dose by Maintenance Dose Regimen
|
Maintenance Dose |
|||
|
Parameters |
1.5 mg/kg once every week |
3 mg/kg once every two weeks |
6 mg/kg once every four weeks |
|
Cmax, ss (µg/mL) |
55.1 ± 15.9 |
58.3 ± 16.4 |
67 ± 17.7 |
|
AUCss,τ (µg/mL*day) |
376 ± 109 |
752 ± 218 |
1503 ± 437 |
|
Ctrough, ss (µg/mL) |
51.2± 15.2 |
46.9 ± 14.8 |
38.5 ± 14.2 |
|
Cmax/ Ctrough ratio (µg/mL) |
1.08 ± 0.03 |
1.26 ± 0.12 |
1.85 ± 0.47 |
| AUCss,τ = area under the concentration time curve at steady-state over the dosing interval (τ = 1, 2, or 4 weeks); Cmax, ss = maximum plasma concentration at steady state; Ctrough, ss = trough concentration at steady state. | |||
Following subcutaneous administration, the mean (± SD) absorption half-life was 1.6 ± 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)].
The mean apparent volume of distribution (% coefficient of variation [%CV]) was 10.4 L (26.0%).
The mean apparent clearance (%CV) was 0.27 L/day (28.4%) and the mean elimination apparent half-life (± SD) was 26.9 ± 9.1 days.
The pharmacokinetics of emicizumab-kxwh are not influenced by age (1 year to 77 years), race (White 62.7%, Asian 22.9%, and Black 8%), inhibitor status (inhibitor present, 50%), mild hepatic impairment (defined as total bilirubin 1x to ≤1.5x the upper limit of normal (ULN) and any aspartate transaminase (AST) level), moderate hepatic impairment (defined as total bilirubin 1.5x to ≤3x the ULN and any AST level), mild renal impairment (defined as creatinine clearance
(CrCl) of 60 – 89 mL/min), and moderate renal impairment (defined as CrCl of 30 – 59 mL/min). Emicizumab-kxwh has not been studied in patients with severe hepatic or renal impairment.
In pediatric patients less than 6 months old, the predicted concentrations of emicizumab-kxwh were 19% to 33% lower than the older patients, especially with the 3 mg/kg once every two weeks or 6 mg/kg once every four weeks maintenance dose.
Body weight: The apparent clearance and volume of distribution of emicizumab-kxwh increased with increasing body weight (9 kg to 156 kg). Dosing in mg/kg provides similar emicizumabkxwh exposure across body weight range.
No drug-drug interaction studies have been conducted with HEMLIBRA.
The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of HEMLIBRA or of other emicizumab products.
In the clinical trials with HEMLIBRA, 5.1% of patients (34/668) tested positive for antiemicizumab-kxwh antibodies. Participants were exposed to emicizumab-kxwh for a median interquartile range (IQR) of 103.1 (82.4 – 148.1) weeks. Samples testing for anti-drug antibodies were obtained at baseline and at trough periodically throughout the studies duration.
Antibody positive samples were further evaluated for neutralizing anti-emicizumab-kxwh antibodies using a modified FVIII chromogenic assay. A total of 668 patients were tested for anti-emicizumab-kxwh antibodies. 5.1% of patients (34/668) tested positive for antiemicizumab-kxwh antibodies and 2.7% of patients (18/668) developed anti-emicizumab-kxwh antibodies that were neutralizing in vitro. Of these, 2.7% of patients (18/668), the neutralizing anti-emicizumab-kxwh antibodies did not have a clinically meaningful impact on the pharmacokinetics of HEMLIBRA in 2.1% of patients (14/668), while decreased emicizumabkxwh plasma concentrations were observed in 0.6% of patients (4/668).
One patient (1/668; 0.1%) developed neutralizing anti-emicizumab-kxwh antibodies and had decreased emicizumab-kxwh plasma concentrations, and experienced loss of efficacy (manifest as breakthrough bleeding) after 5 weeks of treatment and discontinued HEMLIBRA treatment.
[see Warnings and Precautions (5.3), Clinical Studies (14.3)].
MEDICATION GUIDE
HEMLIBRA® (hem-lee-bruh)
(emicizumab-kxwh) injection,
for subcutaneous use
What is the most important information I should know about HEMLIBRA?
HEMLIBRA increases the potential for your blood to clot. Carefully follow your healthcare provider’s instructions regarding when to use an on-demand bypassing agent or factor VIII (FVIII) and the recommended dose and schedule to use for breakthrough bleed treatment.
HEMLIBRA may cause the following serious side effects when used with activated prothrombin complex concentrate (aPCC; FEIBA®), including:
|
|
|
|
If aPCC (FEIBA®) is needed, talk to your healthcare provider in case you feel you need more than 100 U/kg of aPCC (FEIBA®) total.
Your body may make antibodies against HEMLIBRA, which may stop HEMLIBRA from working properly. Contact your healthcare provider immediately if you notice that HEMLIBRA has stopped working for you (e.g. increase in bleeds).
See “What are the possible side effects of HEMLIBRA?” for more information about side effects.
What is HEMLIBRA?
HEMLIBRA is a prescription medicine used for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children, ages newborn and older, with hemophilia A with or without factor VIII inhibitors.
Hemophilia A is a bleeding condition people can be born with where a missing or faulty blood clotting factor (factor VIII) prevents blood from clotting normally.
HEMLIBRA is a therapeutic antibody that bridges clotting factors to help your blood clot.
Before using HEMLIBRA, tell your healthcare provider about all of your medical conditions, including if you:
Tell your healthcare provider about all the medicines you take, including prescription medicines, over-the-counter medicines, vitamins, or herbal supplements. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.
How should I use HEMLIBRA?
See the detailed “Instructions for Use” that comes with your HEMLIBRA for information on how to prepare and inject a dose of HEMLIBRA, and how to properly throw away (dispose of) used needles and syringes.
What are the possible side effects of HEMLIBRA?
The most common side effects of HEMLIBRA include:
These are not all of the possible side effects of HEMLIBRA.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store HEMLIBRA?
Keep HEMLIBRA and all medicines out of the reach of children.
General information about the safe and effective use of HEMLIBRA.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use HEMLIBRA for a condition for which it was not prescribed. Do not give HEMLIBRA to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about HEMLIBRA that is written for health professionals.
What are the ingredients in HEMLIBRA? Active ingredient: emicizumab-kxwh
Inactive ingredients: L-arginine, L-histidine, poloxamer 188, and L-aspartic acid.
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 ©2025 Genentech, Inc. All rights reserved.
For more information, go to www.HEMLIBRA.com or call 1-866-HEMLIBRA.
This Medication Guide has been approved by the U.S. Food and Drug Administration
