Data from FDA - Curated by EPG Health - Last updated 08 May 2018

Indication(s)

1 INDICATIONS AND USAGE HEMLIBRA is 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. 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. (1)

Learning Zones

An epgonline.org Learning Zone (LZ) is an area of the site dedicated to providing detailed self-directed medical education about a disease, condition or procedure.

Oral Anticoagulation Reversal

Oral Anticoagulation Reversal

Experts discuss the use of non-vitamin K oral anticoagulants in the treatment and prevention of stroke, deep vein thrombosis and pulmonary embolism in atrial fibrillation patients.

Chronic Lymphocytic Leukaemia (CLL)

Chronic Lymphocytic Leukaemia (CLL)

Refine your knowledge of chronic lymphocytic leukaemia (CLL) with information on pathophysiology, diagnosis, treatment options and more

+ 1 more

Acute and Advanced Heart Failure

Acute and Advanced Heart Failure

What are the most effective treatments for acute heart failure? Can you define advanced heart failure? Discover here...

+ 3 more

Load more

Related Content

Advisory information

contraindications
4 CONTRAINDICATIONS None. None (4)
Adverse reactions
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. 6.1 Clinical Trials Experience 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 a randomized trial (HAVEN 1), single-arm trial (HAVEN 2), and a dose-finding trial, in which a total of 189 male patients with hemophilia A received at least one dose of HEMLIBRA as routine prophylaxis. Ninety-four patients (50%) were adults (18 years and older), 38 (20%) were adolescents (12 years up to less than 18 years), 55 (29%) were children (2 years up to less than 12 years), and two (1%) were infants (1 month up to less than 2 years). Seven of the 189 patients (4%) included in the safety population were patients without FVIII inhibitors from the dose-finding trial. The median duration of exposure across the studies was 38 weeks (0.8 to 177.2 weeks). The most frequently reported adverse reactions observed in ≥ 10% of patients treated with at least one dose of HEMLIBRA were injection site reactions, headache, and arthralgia. Four patients (2.1%) in the clinical trials receiving HEMLIBRA prophylaxis withdrew from treatment due to adverse reactions, which were thrombotic microangiopathy, skin necrosis and superficial thrombophlebitis, 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 n (%) (N = 189) General Disorders and Administration Site Conditions Injection site reactionIncludes 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 urticarial, and injection site warmth. 35 (19%) Pyrexia 13 (7%) Nervous System Disorders Headache 28 (15%) Gastrointestinal Disorders Diarrhea 12 (6%) Musculoskeletal and Connective Tissue Disorders Arthralgia 18 (10%) Myalgia 9 (5%) Characterization of aPCC treatment in pooled clinical trials There were 125 instances of aPCC treatment in 36 patients, of which 13 instances (10.4%) 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 TreatmentAn 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. 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 7 76 18 24 – 48 hours 0 6 3Thrombotic event > 48 hours 1 4 10Thrombotic microangiopathy , , , Injection Site Reactions In total, 35 patients (19%) reported injection site reactions (ISRs). All ISRs observed in HEMLIBRA clinical trials were reported as mild to moderate intensity and 88% resolved without treatment. The commonly reported ISR symptoms were injection site erythema (7.4%), injection site pruritus (5.3%), and injection site pain (5.3%). 6.2 Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying disease. For these reasons, comparison of the incidence of antibodies to emicizumab-kxwh in the studies described below with the incidence of antibodies in other studies or to other products may be misleading. The immunogenicity of HEMLIBRA was evaluated using an enzyme-linked immunosorbent assay (ELISA) or an electrochemiluminescence (ECL) assay. No patients tested positive for anti-emicizumab antibodies in HAVEN 1 and HAVEN 2 (n = 171). Four patients tested positive for anti-emicizumab antibodies in the dose-finding trial (n = 18). The anti-emicizumab antibody positive rate may be under-reported due to the limitation of the assay.

Usage information

Dosing and administration
2 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. (2.1) See Full Prescribing Information for important preparation and administration instructions. (2.2) 2.1 Recommended Dosage For subcutaneous use only. The recommended dose is 3 mg/kg by subcutaneous injection once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly. Missed Dose If a dose of HEMLIBRA is not administered on the scheduled day, administer as soon as possible before the day of the next scheduled dose, and then resume usual weekly dosing schedule. Do not double doses to make up for a missed dose. 2.2 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 aged less than 7 years old. The HEMLIBRA "Instructions for Use" contains more detailed instructions on the preparation and administration of HEMLIBRA [see Instructions for Use]. Visually inspect HEMLIBRA for particulate matter and discoloration before administration. HEMLIBRA for subcutaneous administration is a colorless to slightly yellow solution. Do not use if particulate matter is visible or product is discolored. A syringe, a transfer needle, and an injection needle are needed to withdraw HEMLIBRA solution from the vial and inject it subcutaneously. Refer to the HEMLIBRA "Instructions for Use" for handling instructions when combining vials. Do not use different HEMLIBRA vials of different concentrations when combining vials to administer prescribed dose. Administer doses of HEMLIBRA up to 1 mL with a 1 mL syringe. A 1 mL syringe fulfilling the following criteria may be used: Transparent polypropylene or polycarbonate syringe with Luer-Lok™ tip, graduation 0.01 mL, sterile, for injection only, single-use, latex-free and non-pyrogenic, commercially available in the US. Administer doses of HEMLIBRA greater than 1 mL and up to 2 mL with a 2 mL or 3 mL syringe. A 2 mL or 3 mL syringe fulfilling the following criteria may be used: Transparent polypropylene or polycarbonate syringe with Luer-Lok™ tip, graduation 0.1 mL, sterile, for injection only, single-use, latex-free, and non-pyrogenic, commercially available in the US. A transfer needle fulfilling the following criteria may be used: Stainless steel needle with Luer-Lok™ connection, sterile, 18 gauge, length 1½ inch, semi-blunted tip, single-use, latex-free, and non-pyrogenic, commercially available in the US. An injection needle fulfilling the following criteria may be used: Stainless steel with Luer-Lok™ connection, sterile, 26 gauge, maximal length ½ inch, single-use, latex-free and non-pyrogenic, including needle safety feature, commercially available in the US. Administer each injection at a different anatomic location (upper outer arms, thighs, or any quadrant of abdomen) than the previous injection. An injection should never be given into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact. Administration of HEMLIBRA in the upper outer arm should only be performed by a caregiver or healthcare provider. Discard any unused HEMLIBRA remaining in the single-dose vial.
Use in special populations
8 USE IN SPECIFIC POPULATIONS 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. 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 – 4% and 15 – 20%, respectively. 8.2 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.

Interactions

7 DRUG INTERACTIONS 7.1 Hypercoagulability with Concomitant Use of aPCC, rFVIIa, or FVIII Clinical experience suggests that a drug interaction exists with HEMLIBRA and aPCC [see Warnings and Precautions (5.1, 5.2)]. There is a possibility for hypercoagulability with rFVIIa or FVIII with HEMLIBRA based on preclinical experiments. 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. 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, single-factor 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 false-negative 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)].

More information

Category Value
Authorisation number BLA761083
Agency product number 7NL2E3F6K3
Orphan designation No
Product NDC 50242-920,50242-921,50242-922,50242-923
Date Last Revised 21-11-2017
Type HUMAN PRESCRIPTION DRUG
Storage and handling Storage and Handling 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. Prior to administration, if needed, unopened vials of HEMLIBRA may be stored out of and then returned to refrigeration. The temperature and total combined time out of refrigeration should not exceed 30°C (86°F) and 7 days (at a temperature below 30°C [86°F]), respectively. Once removed from the vial, discard HEMLIBRA if not used immediately. Discard any unused HEMLIBRA.
Marketing authorisation holder Genentech, Inc.
Warnings 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. WARNING: THROMBOTIC MICROANGIOPATHY and THROMBOEMBOLISM See full prescribing information for complete boxed warning. 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 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.