Hemlibra

Hemlibra

emicizumab

Manufacturer:

Roche

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Emicizumab.
Description
Hemlibra 30 mg/mL solution for injection: Each mL of solution contains 30 mg of emicizumab*.
Each vial of 1 mL contains 30 mg of emicizumab at a concentration of 30 mg/mL.
Hemlibra 150 mg/mL solution for injection: Each mL of solution contains 150 mg of emicizumab*.
Each vial of 0.4 mL contains 60 mg of emicizumab at a concentration of 150 mg/mL.
Each vial of 0.7 mL contains 105 mg of emicizumab at a concentration of 150 mg/mL.
Each vial of 1 mL contains 150 mg of emicizumab at a concentration of 150 mg/mL.
*produced by recombinant DNA technology using mammalian Chinese Hamster Ovary (CHO) cell culture.
Excipients/Inactive Ingredients: L-Arginine, L-Histidine, L-Aspartic acid, Poloxamer 188, Water for injections.
Action
Pharmacotherapeutic group: antihemorrhagics, other systemic hemostatics. ATC code: B02BX06.
Pharmacology: Mechanism of action: Emicizumab bridges activated factor IX and factor X to restore the function of missing activated factor VIII that is needed for effective haemostasis.
Emicizumab has no structural relationship or sequence homology to factor VIII and, as such, does not induce or enhance the development of direct inhibitors to factor VIII.
Pharmacodynamics: Prophylactic therapy with Hemlibra shortens the aPTT and increases the reported factor VIII activity (using a chromogenic assay with human coagulation factors). These two pharmacodynamic markers do not reflect the true haemostatic effect of emicizumab in vivo (aPTT is overly shortened and reported factor VIII activity may be overestimated) but provide a relative indication of the pro-coagulant effect of emicizumab.
Clinical efficacy and safety: Patients (aged 12 to 75 years old) with haemophilia A with factor VIII inhibitors (Study BH29884): Hemlibra prophylaxis was evaluated in a randomised, multicentre, open-label clinical study in 109 adolescent and adult males (aged 12 to 75 years old) with haemophilia A with factor VIII inhibitors who had previously received either episodic or prophylactic treatment with bypassing agents (aPCC and rFVIIa). In the study, patients received weekly Hemlibra prophylaxis (Arms A, C, and D) - 3 mg/kg once weekly for 4 weeks followed by 1.5 mg/kg once weekly thereafter - or no prophylaxis (Arm B). Dose up-titration to 3 mg/kg once weekly was allowed after 24 weeks on Hemlibra prophylaxis in case of suboptimal efficacy (i.e. ≥ 2 spontaneous and clinically significant bleeds). During the study, two patients underwent up-titration of their maintenance dose to 3 mg/kg once weekly.
Fifty-three patients previously treated with episodic (on-demand) bypassing agents were randomised in a 2:1 ratio to receive Hemlibra prophylaxis (Arm A) or no prophylaxis (Arm B), with stratification by prior 24-week bleed rate (< 9 or ≥ 9). Patients randomised to Arm B could switch to Hemlibra after completing at least 24 weeks without prophylaxis.
Forty-nine patients previously treated with prophylactic bypassing agents were enrolled in Arm C to receive Hemlibra prophylaxis. Patients previously treated with episodic (on-demand) bypassing agents who had participated in the non-interventional study (NIS) prior to enrolment but were unable to enroll in Study BH29884 prior to the closure of Arms A and B were enrolled in Arm D to receive Hemlibra prophylaxis. The NIS is an observational study with the main objective of capturing detailed clinical data on the bleeding episodes and haemophilia medication use of patients with haemophilia A outside of an interventional trial setting.
The primary objective of the study was to evaluate, among patients previously treated with episodic (on-demand) bypassing agents, the treatment effect of weekly Hemlibra prophylaxis compared with no prophylaxis (Arm A vs. Arm B) on the number of bleeds requiring treatment with coagulation factors over time (minimum of 24 weeks or date of discontinuation). Other secondary objectives of the randomised comparison of Arms A and B were the efficacy of weekly Hemlibra prophylaxis in reducing the number of all bleeds, spontaneous bleeds, joint bleeds and target joint bleeds, as well as assessing patients' health-related quality of life and health status. The mean exposure time (+SD) for all patients on study was 21.38 weeks (12.01). For each treatment arm, the mean exposure times (+SD) were 28.86 weeks (8.37) for Arm A, 8.79 (3.62) for Arm B, 21.56 (11.85) for Arm C and 7.08 (3.89) for Arm D. One patient in Arm A withdrew from study prior to initiation of Hemlibra.
The study also evaluated the efficacy of weekly Hemlibra prophylaxis compared with previous episodic (ondemand) and prophylactic bypassing agents (separate comparisons) in patients who had participated in the NIS prior to enrolment (Arms A and C, respectively). Only patients from the NIS were included in this comparison, because bleed and treatment data were collected with the same level of granularity in both periods.
In Study BH29884, all primary and secondary objectives were met (see as follows Tables 1 and 2).

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In the intra-patient analysis, Hemlibra prophylaxis resulted in statistically significant (p = 0.0003) and clinically meaningful reduction (79%) in bleed rate for treated bleeds compared with previous bypassing agent prophylaxis collected in the NIS prior to enrolment (see Table 2).

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In Study BH29884, health-related quality of life for patients aged ≥ 18 years was evaluated at Week 25 based on the Haemophilia-specific Quality of Life (Haem-A-QoL) questionnaire for adults. Baseline Total Scores (mean = 41.14 and 44.58, respectively) and Physical Health scale scores (mean = 52.41 and 57.19, respectively) were similar for Hemlibra prophylaxis and no prophylaxis. Table 3 provides a summary of the comparison between the Hemlibra prophylaxis arm (Arm A) and the no prophylaxis arm (Arm B) on the Haem-A-QoL Total Score and Physical Health scale after 24 weeks of treatment adjusting for baseline. Weekly Hemlibra prophylaxis showed a statistically significant and clinically meaningful improvement compared with the no prophylaxis in the pre-specified endpoints of Haem-A-QoL Total Score and Physical Health Scale score at the Week 25 assessment. (See Table 3.)

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In Study BH29884, patients' health status was assessed according to the EuroQoL Five-Dimension-Five Levels Questionnaire (EQ-5D-5L). Table 4 provides a summary of the comparison between the Hemlibra prophylaxis arm (Arm A) and the no prophylaxis arm (Arm B) on the EQ-5D-5L index utility scale and visual analog scale after 24 weeks of treatment adjusting for baseline. Weekly Hemlibra showed a statistically significant and clinically meaningful improvement compared with no prophylaxis in the pre specified endpoints of EQ-5D-5L index utility scale and visual analogue scale at the Week 25 assessment. (See Table 4.)

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Paediatric patients (age < 12 years old, or 12 to 17 years old weighing < 40 kg) with haemophilia A with factor VIII inhibitors (Study BH29992) (Interim Analysis): Hemlibra weekly prophylaxis was evaluated in a single-arm, multicentre, open-label clinical study in paediatric patients (age < 12 years old, or 12 to 17 years old weighing < 40 kg) with haemophilia A with factor VIII inhibitors. Patients received Hemlibra prophylaxis at 3 mg/kg once weekly for the first 4 weeks followed by 1.5 mg/kg once weekly thereafter.
The study evaluated the pharmacokinetics, safety, and efficacy including the efficacy of weekly Hemlibra prophylaxis compared with previous episodic and prophylactic bypassing agent treatment in patients who had participated in the NIS prior to enrolment (intra-patient comparison).
At the time of the interim analysis, the clinical study had enrolled 60 male patients. Two patients aged < 2 years old, 17 patients aged 2 to < 6 years, 38 patients aged 6 to < 12 years and 3 patients aged ≥ 12 years, resulting in 57 patients that were < 12 years old and evaluable for efficacy. The annualized bleed rate and percent of patients with zero bleeds were calculated for 23 patients <12 years old who received weekly Hemlibra prophylaxis for at least 12 weeks (see Table 4). The median observation time for these patients was 38.1 weeks (range: 12.7 to 41.6 weeks).
The interim analysis efficacy results for Study BH29992 are summarised as follows (see Tables 5 and 6). In total 20 of 23 (87%) patients had zero treated bleeds and 8 of 23 (34.8%) did not have any bleeds while receiving Hemlibra prophylaxis (see Table 5).

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In the intra-patient analysis, Hemlibra weekly prophylaxis resulted in a clinical meaningful reduction (99%) in treated bleed rate in thirteen paediatric patients after at least 12 weeks of treatment compared to their bleed rate collected in the NIS prior to enrolment. (See Table 6.)

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There is limited experience with bypassing agent use during surgeries and procedures. Bypassing agent use during surgeries and procedures was determined by the investigator.
Immunogenicity: As with all therapeutic proteins, there is the potential for an immune response in patients treated with emicizumab. A total of 189 patients were tested for anti-emicizumab antibodies in the clinical trials. Four patients (2.1%) tested positive for anti-emicizumab antibodies in the phase I/II trials, all of which were non-neutralising.
The data reflect the number of patients whose test results were considered positive for antibodies to emicizumab using an enzyme-linked immunosorbent assay (ELISA). Immunogenicity assay results may be influenced by several factors including assay sensitivity and specificity, sample handling, timing of sample collection, concomitant medicinal products and underlying disease. For these reasons, comparison of incidence of antibodies to emicizumab with the incidence of antibodies to other products may be misleading.
In case of clinical signs of loss of efficacy, a change of treatment should be considered.
Pharmacokinetics: The pharmacokinetics of emicizumab was determined via non-compartmental analysis in healthy subjects and using a population pharmacokinetic analysis on a database composed of 141 patients with haemophilia A.
Absorption: Following subcutaneous administration in haemophilia A patients, the absorption half-life was 1.7 days.
Following multiple subcutaneous administrations of 3 mg/kg once weekly for the first 4 weeks in haemophilia A patients, mean (±SD) trough plasma concentrations of emicizumab increased to achieve 54.6±14.3 μg/mL at Week 5. Trough plasma concentrations of approximately 50 μg/mL were sustained thereafter with weekly dosing of 1.5 mg/kg (see figure).

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The predicted mean (±SD) Ctrough and Cmax at steady state were 52.2±13.5 μg/mL and 56.5±13.5 μg/mL, respectively. The mean (±SD) ratio of Cmax/Ctrough at steady state was 1.07±0.03.
In healthy subjects, the absolute bioavailability following subcutaneous administration of 1 mg/kg was between 80.4% and 93.1% depending on the injection site. Similar pharmacokinetic profiles were observed following subcutaneous administration in the abdomen, upper arm, and thigh. Emicizumab can be administered interchangeably at these anatomical sites (see Dosage & Administration).
Distribution: Following a single intravenous dose of 0.25 mg/kg emicizumab in healthy subjects, the volume of distribution at steady state was 106 mL/kg (i.e. 7.4 L for a 70-kg adult).
The apparent volume of distribution (V/F), estimated from the population PK analysis, in haemophilia A patients following multiple subcutaneous doses of emicizumab was 11.4 L.
Metabolism: The metabolism of emicizumab has not been studied. IgG antibodies are mainly catabolised by lysosomal proteolysis and then eliminated from or reused by the body.
Elimination: Following intravenous administration of 0.25 mg/kg in healthy subjects, the total clearance of emicizumab was 3.26 mL/kg/day (i.e. 0.228 L/d for a 70-kg adult) and the mean terminal half-life was 26.7 days.
Following single subcutaneous injection in healthy subjects, the elimination half-life was approximately 4 to 5 weeks.
Following multiple subcutaneous injections in haemophilia A patients, the apparent clearance was 0.244 L/day and the elimination apparent half-life was 27.8 days.
Dose linearity: Emicizumab exhibited dose-proportional pharmacokinetics in patients with haemophilia A over a dose range from 0.3 to 3 mg/kg once weekly following subcutaneous administration.
Special populations: Paediatric: The effect of age on the pharmacokinetics of emicizumab was assessed in a population pharmacokinetic analysis which included 59 children (less than 12 years) and 38 adolescents (12 to 17 years) with haemophilia A. An additional descriptive analysis of pharmacokinetic data collected from Study BH29992 was performed in two infants (1 month to < 2 years), 55 children (≥ 2 years to < 12 years) and 3 adolescents (12 to 17 years).
Age did not affect the pharmacokinetics of emicizumab in paediatric patients.
Elderly: The effect of age on the pharmacokinetics of emicizumab was assessed in a population pharmacokinetic analysis which included three subjects aged 65 years and older (no subjects were older than 75 years of age). Clearance increased with older age, but no clinically important differences were observed in the pharmacokinetics of emicizumab between subjects < 65 years and subjects ≥ 65 years.
Race: Population pharmacokinetics analyses in patients with haemophilia A showed that race did not affect the pharmacokinetics of emicizumab. No dose adjustment is required for this demographic factor.
Renal impairment: No dedicated studies of the effect of renal impairment on the pharmacokinetics of emicizumab have been conducted.
The safety and efficacy of emicizumab have not been specifically tested in patients with renal impairment. There are limited data available on the use of Hemlibra in patients with mild renal impairment. No data are available on the use of Hemlibra in patients with moderate to severe renal impairment. Mild renal impairment did not affect the pharmacokinetics of emicizumab.
Emicizumab is a monoclonal antibody and is cleared via catabolism rather than renal excretion and a change in dose is not expected to be required for patients with renal impairment.
Hepatic impairment: No dedicated studies on the effect of hepatic impairment on the pharmacokinetics of emicizumab have been conducted. Most of the patients with haemophilia A in the population pharmacokinetic analysis had normal hepatic function (bilirubin and AST ≤ ULN, n=113) or mild hepatic impairment (bilirubin ≤ ULN and AST > ULN or bilirubin < 1.0 to 1.5 × ULN and any AST, n=17). Mild hepatic impairment did not affect the pharmacokinetics of emicizumab (see Dosage & Administration). The safety and efficacy of emicizumab have not been specifically tested in patients with hepatic impairment. Patients with mild and moderate hepatic impairment were included in clinical trials. No data are available on the use of Hemlibra in patients with severe hepatic impairment.
Emicizumab is a monoclonal antibody and cleared via catabolism rather than hepatic metabolism and a change in dose is not expected to be required for patients with hepatic impairment.
Toxicology: Preclinical safety data: Preclinical data reveal no special hazards for humans based on studies of acute and repeated dose toxicity, including safety pharmacology endpoints and endpoints for reproductive toxicity.
Fertility: Emicizumab did not cause any changes in the reproductive organs of male or female cynomolgus monkeys up to the highest tested dose of 30 mg/kg/week (equivalent to 11 times the human exposure at the highest dose of 3 mg/kg/week, based on AUC).
Teratogenicity: No data are available with respect to potential side effects of emicizumab on embryo-foetal development.
Injection site reactions: Reversible hemorrhage, perivascular mononuclear cell infiltration, degeneration/necrosis of subcutis and swelling of endothelium in the subcutis was noted in animals after subcutaneous injection.
Indications/Uses
Hemlibra is indicated for routine prophylaxis of bleeding episodes in patients with haemophilia A with factor VIII inhibitors.
Hemlibra can be used in all age groups.
Dosage/Direction for Use
Treatment should be initiated under the supervision of a physician experienced in the treatment of haemophilia and/or bleeding disorders.
Posology: Treatment (including routine prophylaxis) with bypassing agents (e.g. aPCC and rFVIIa) should be discontinued the day before starting Hemlibra therapy (see Precautions).
The recommended dose is 3 mg/kg once weekly for the first 4 weeks (loading dose), followed by 1.5 mg/kg once weekly (maintenance dose), administered as a subcutaneous injection.
The patient dose (in mg) and volume (in mL) should be calculated as follows: Loading dose (3 mg/kg) once weekly for the first 4 weeks: Patient bodyweight (kg) x dose (3 mg/kg) = total amount (mg) of emicizumab to be administered.
Followed by a maintenance dose (1.5 mg/kg) once weekly from week 5 on: Patient bodyweight (kg) x dose (1.5 mg/kg) = total amount (mg) of emicizumab to be administered.
The total volume of Hemlibra to be injected subcutaneously is calculated as follows: Total amount (mg) of emicizumab to be administered ÷ vial concentration (mg/mL) = total volume of Hemlibra (mL) to be injected.
Different Hemlibra concentrations (30 mg/mL and 150 mg/mL) should not be combined when making up the total volume to be administered.
A volume greater than 2 mL per injection should not be administered.
Examples: Patient's bodyweight of 60 kg: Loading dose (first 4 weeks) example: 60 kg x 3 mg/kg = 180 mg of emicizumab needed for the loading dose.
To calculate the volume to be administered divide calculated dose 180 mg by 150 mg/mL: 180 mg of emicizumab ÷ 150 mg/mL = 1.20 mL of 150 mg/mL Hemlibra concentration to be injected.
Choose appropriate dosage and volume from vial strengths available.
Maintenance dose (from week 5 on) example: 60 kg x 1.5 mg/kg = 90 mg of emicizumab needed for the maintenance dose.
To calculate the volume to be administered divide calculated dose 90 mg by 150 mg/mL: 90 mg of emicizumab ÷ 150 mg/mL = 0.6 mL of 150 mg/mL Hemlibra concentration to be injected.
Choose appropriate dosage and volume from vial strengths available.
Patient's bodyweight of 16 kg: Loading dose (first 4 weeks) example: 16 kg x 3 mg/kg = 48 mg of emicizumab needed for the loading dose.
To calculate the volume to be administered divide calculated dose 48 mg by 150 mg/mL: 48 mg of emicizumab ÷ 150 mg/mL = 0.32 mL of 150 mg/mL Hemlibra concentration to be injected.
Choose appropriate dosage and volume from vial strengths available.
Maintenance dose (from week 5 on) example: 16 kg x 1.5 mg/kg = 24 mg of emicizumab needed for the maintenance dose.
To calculate the volume to be administered divide calculated dose 24 mg by 30 mg/mL: 24 mg of emicizumab ÷ 30 mg/mL = 0.8 mL of 30 mg/mL Hemlibra concentration to be injected.
Choose appropriate dosage and volume from vial strength available.
Duration of treatment: Hemlibra is intended for long-term prophylactic treatment.
Dosage adjustments during treatment: No dosage adjustments of Hemlibra are recommended.
Delayed or missed doses: If a patient misses a scheduled weekly subcutaneous injection of Hemlibra, the patient should be instructed to take the missed dose as soon as possible, up to a day before the day of the next scheduled dose. The patient should then administer the next dose on the usual scheduled dosing day. The patient should not take a double dose to make up for a missed dose.
Special populations: Paediatric: No dose adjustments are recommended in paediatric patients (see Pharmacology: Pharmacokinetics under Actions). There are no data in patients less than 1 year of age.
Elderly: No dose adjustments are recommended in patients ≥ 65 years of age (see Pharmacology: Pharmacokinetics under Actions). There are no data in patients over 75 years old.
Renal and hepatic impairment: No dose adjustments are recommended in patients with mild renal or mild and moderate hepatic impairment (see Pharmacology: Pharmacokinetics under Actions). Emicizumab has not been studied in patients with moderate or severe renal impairment or severe hepatic impairment.
Management in the perioperative setting: The safety and efficacy of emicizumab have not been formally evaluated in the surgical setting. If bypassing agents (e.g. aPCC and rFVIIa) are required in the perioperative period, please refer to the dosing guidance on the use of bypassing agents in Precautions.
Immune tolerance induction (ITI): The safety and efficacy of emicizumab in patients receiving ongoing immune tolerance induction have not yet been established. No data are available.
Method of administration: Hemlibra is for subcutaneous use only, and it should be administered using appropriate aseptic technique (see Special precautions for disposal and other handling under Cautions for Usage).
The injection should be restricted to the recommended injection sites: the abdomen, the upper outer arms and the thighs (see Pharmacology: Pharmacokinetics under Actions).
Administration of Hemlibra subcutaneous injection in the upper outer arm should be performed by a caregiver or healthcare professional.
Alternating the site of injection may help prevent or reduce injection site reactions (see Adverse Reactions). Hemlibra subcutaneous injection should not be administered into areas where the skin is red, bruised, tender or hard, or areas where there are moles or scars.
During treatment with Hemlibra, other medicinal products for subcutaneous administration should, preferably, be injected at different anatomical sites.
Administration by the patient and/or caregiver: Hemlibra is intended for use under the guidance of a healthcare professional. After proper training in subcutaneous injection technique, a patient may self-inject Hemlibra, or the patient's caregiver may administer it, if their physician determines that it is appropriate.
The physician and the caregiver should determine the appropriateness of the child self-injecting Hemlibra. However, self-administration is not recommended for children below 7 years of age.
For comprehensive instructions on the administration of Hemlibra, see Special precautions for disposal and other handling under Cautions for Usage and package leaflet.
Overdosage
There is limited experience with overdose of Hemlibra.
Symptoms: Accidental overdose may result in hypercoagulability.
Management: Patients who receive an accidental overdose should immediately contact their physician and be monitored closely.
Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in Excipients/Inactive Ingredients under Description.
Special Precautions
Traceability: In order to improve traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Thrombotic microangiopathy associated with Hemlibra and activated prothrombin complex concentrate: Cases of thrombotic microangiopathy (TMA) were reported from a clinical trial in patients receiving Hemlibra prophylaxis when on average a cumulative amount of >100U/kg/24 hours of activated prothrombin complex concentrate (aPCC) for 24 hours or more was administered (see Adverse Reactions). Treatment for the TMA events included supportive care with or without plasmapheresis and haemodialysis. Evidence of improvement was seen within one week following discontinuation of aPCC and interruption of Hemlibra. This rapid improvement is distinct from the usual clinical course observed in atypical hemolytic uremic syndrome and classic TMAs, such as thrombotic thrombocytopenic purpura (see Adverse Reactions). One patient resumed Hemlibra following resolution of TMA and continued to be treated safely.
Patients receiving Hemlibra prophylaxis should be monitored for the development of TMA when administering aPCC. The physician should immediately discontinue aPCC and interrupt Hemlibra therapy if clinical symptoms and/or laboratory findings consistent with TMA occur, and manage as clinically indicated. Physicians and patients/caregivers should weigh the benefits and risks of resuming Hemlibra prophylaxis following complete resolution of TMA on a case-by-case basis. In case a bypassing agent is indicated in a patient receiving Hemlibra prophylaxis, see as follows for dosing guidance on the use of bypassing agents.
Caution should be used when treating patients who are at high risk for TMA (e.g. have a previous medical history or family history of TMA), or those who are receiving concomitant medications known to be a risk factor for the development of TMA (e.g. ciclosporin, quinine, tacrolimus).
Thromboembolism associated with Hemlibra and activated prothrombin complex concentrate: Serious thrombotic events were reported from a clinical trial in patients receiving Hemlibra prophylaxis when on average a cumulative amount of >100U/kg/24 hours of aPCC for 24 hours or more was administered (see Adverse Reactions). No cases required anticoagulation therapy. Following discontinuation of aPCC and interruption of Hemlibra, evidence of improvement or resolution was seen within one month (see Adverse Reactions). One patient resumed Hemlibra following resolution of thrombotic event and continued to be treated safely.
Patients receiving Hemlibra prophylaxis should be monitored for the development of thromboembolism when administering aPCC. The physician should immediately discontinue aPCC and interrupt Hemlibra therapy if clinical symptoms, imaging, and/or laboratory findings consistent with thrombotic events occur, and manage as clinically indicated. Physicians and patients/caregivers should weigh the benefits and risks of resuming Hemlibra prophylaxis following complete resolution of thrombotic events on a case-by-case basis. In case a bypassing agent is indicated in a patient receiving Hemlibra prophylaxis, see as follows for dosing guidance on the use of bypassing agents.
Guidance on the use of bypassing agents in patients receiving Hemlibra prophylaxis: Treatment with bypassing agents should be discontinued the day before starting Hemlibra therapy.
Physicians should discuss with all patients and/or caregivers the exact dose and schedule of bypassing agents to use, if required while receiving Hemlibra prophylaxis.
Hemlibra increases the patient's coagulation potential. The bypassing agent dose required may therefore be lower than that used without Hemlibra prophylaxis. The dose and duration of treatment with bypassing agents will depend on the location and extent of bleeding, and the patient's clinical condition. Use of aPCC should be avoided unless no other treatment options/alternatives are available. If aPCC is indicated in a patient receiving Hemlibra prophylaxis, the initial dose should not exceed 50 U/kg and laboratory monitoring is recommended (including but not restricted to renal monitoring, platelet testing, and evaluation of thrombosis). If bleeding is not controlled with the initial dose of aPCC up to 50 U/kg, additional aPCC doses should be administered under medical guidance or supervision with consideration made to laboratory monitoring for the diagnosis of TMA or thromboembolism and verification of bleeds prior to repeated dosing. The total aPCC dose should not exceed 100 U/kg in the first 24-hours of treatment. Treating physicians must carefully weigh the risk of TMA and thromboembolism against the risk of bleeding when considering aPCC treatment beyond a maximum of 100 U/kg in the first 24-hours.
In clinical trials, no cases of TMA or thrombotic events were observed with use of activated recombinant human FVII (rFVIIa) alone in patients receiving Hemlibra prophylaxis.
Bypassing agent dosing guidance should be followed for at least 6 months following discontinuation of Hemlibra prophylaxis (see Pharmacology: Pharmacokinetics under Actions).
Effects of emicizumab on coagulation tests: Emicizumab replaces the tenase cofactor activity of activated factor VIII (FVIIIa). Coagulation laboratory tests based on intrinsic clotting, including the activated clotting time (ACT), activated partial thromboplastin time (e.g. 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 emicizumab, 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 (see Table 7). However, single factor assays utilising chromogenic or immuno-based methods are not affected by emicizumab and may be used to monitor coagulation parameters during treatment, with specific considerations for FVIII chromogenic activity assays as described as follows.
Chromogenic factor VIII activity tests may be manufactured with either human or bovine coagulation proteins. Assays containing human coagulation factors are responsive to emicizumab but may overestimate the clinical haemostatic potential of emicizumab. In contrast, assays containing bovine coagulation factors are insensitive to emicizumab (no activity measured) and can be used to monitor endogenous or infused factor VIII activity, or to measure anti FVIII inhibitors.
Emicizumab remains active in the presence of inhibitors against factor VIII and so will produce a false negative result in clotting based Bethesda assays for functional inhibition of factor VIII. Instead, a chromogenic Bethesda assay utilising a bovine based factor VIII chromogenic test that is insensitive to emicizumab may be used.
These two pharmacodynamic markers do not reflect the true haemostatic effect of emicizumab in vivo (aPTT is overly shortened and reported factor VIII activity may be overestimated) but provide a relative indication of the pro-coagulant effect of emicizumab.
In summary, intrinsic pathway clotting-based laboratory test results in patients treated with Hemlibra should not be used to monitor its activity, determine dosing for factor replacement or anti -coagulation, or measure factor VIII inhibitors titers. Caution should be taken if intrinsic pathway clotting based laboratory tests are used, as misinterpretation of their results may lead to under-treatment of patients experiencing bleeding episodes, which can potentially result in severe or life-threatening bleeds.
Laboratory tests unaffected by emicizumab are also shown in Table 7 as follows. Due to its long half-life, these effects on coagulation assays may persist for up to 6 months after the last dose (see Pharmacology: Pharmacokinetics under Actions). (See Table 7.)

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Paediatric population: There are no data in children <1 year of age. The developing hemostatic system in neonates and infants is dynamic and evolving, and the relative concentrations of pro- and anticoagulant proteins in these patients should be taken into consideration when making a benefit-risk assessment, including potential risk of thrombosis (e.g. central venous catheter-related thrombosis).
Effects on ability to drive and use machines: Hemlibra has no influence on the ability to drive and use machines.
Use In Pregnancy & Lactation
Women of childbearing potential/Contraception: Women of childbearing potential receiving Hemlibra should use effective contraception during, and for at least 6 months after cessation of Hemlibra treatment (see Pharmacology: Pharmacokinetics under Actions).
Pregnancy: There are no clinical studies of emicizumab use in pregnant women. Animal reproduction studies have not been conducted with Hemlibra. It is not known whether emicizumab can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Hemlibra should be used during pregnancy only if the potential benefit for the mother outweighs the potential risk to the fetus taking into account that, during pregnancy and after parturition, the risk for thrombosis is increased and that several pregnancy complications are linked to an increased risk for disseminated intravascular coagulation (DIC).
Breast-feeding: It is not known whether emicizumab is excreted in human milk. No studies have been conducted to assess the impact of emicizumab on milk production or its presence in breast milk. Human IgG is known to be present in human milk. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Hemlibra therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Fertility: Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see Pharmacology: Toxicology: Preclinical safety data under Actions). No fertility data are available in humans. Thus, the effect of emicizumab on male and female fertility is unknown.
Adverse Reactions
Summary of the safety profile: The most serious adverse drug reactions (ADRs) reported from the clinical trials with Hemlibra were thrombotic microangiopathy (TMA) and thrombotic events, including cavernous sinus thrombosis (CST) and superficial vein thrombosis contemporaneous with skin necrosis (see as follows and Precautions).
The most common ADRs reported in ≥10% of patients treated with at least one dose of Hemlibra were: injection site reactions (19%), headache (15%) and arthralgia (10%).
In total four patients (2.1%) in the clinical trials receiving Hemlibra prophylaxis withdrew from treatment due to ADRs, which were TMA, skin necrosis and superficial thrombophlebitis, and injection site reaction.
Tabulated list of adverse drug reactions: The following adverse drug reactions (ADRs) are based on pooled data from two phase I II clinical trials (Study BH29884 and Study BH29992) and one phase I/II clinical trial (Study ACE002JP), in which a total of 189 male patients with haemophilia A received at least one dose of Hemlibra as routine prophylaxis. Ninety-four patients (50%) were adults. Seven out of the 189 patients (4%) included in the safety population were patients without FVIII inhibitors from the phase I/II clinical trial. The median duration of exposure across the studies was 38 weeks (range: 0.8 to 177.2 weeks).
ADRs from clinical trials in patients who received Hemlibra are listed by MedDRA system organ class (Table 8). The corresponding frequency categories for each ADR are based on the following convention: very common (≥1/10), common (≥1/100 to < 1/10), uncommon (≥1/1,000 to < 1/100), rare (≥1/10,000 to < 1/1,000), very rare (< 1/10,000) and not known (cannot be estimated from the available data). (See Table 8.)

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Description of selected adverse drug reactions: Thrombotic microangiopathy: Thrombotic microangiopathy (TMA) events were reported in 1.6 % of patients (3/189) from clinical trials and in 8.3% of patients (3/36) who received at least one dose of aPCC while being treated with emicizumab. All 3 TMAs occurred when on average a cumulative amount of > 100 U/Kg/24 hours of aPCC for 24 hours or more was administered during a treatment event (see Precautions). Patients presented with thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury, without severe deficiencies in ADAMTS13 activity.
Thrombotic events: Serious thrombotic events were reported in 1.1% of patients (2/189) from clinical trials and in 5.6% of patients (2/36) who received at least one dose of aPCC while being treated with emicizumab. Both serious thrombotic events occurred when on average a cumulative amount of > 100 U/Kg/24 hours of aPCC for 24 hours or more was administered during a treatment event (see Precautions).
Characterization of the interaction between emicizumab and aPCC treatment in pivotal clinical trials: There were 79 instances of aPCC treatment in patients receiving emicizumab prophylaxis, of which eight instances (10.1%) consisted of on average a cumulative amount of >100 U/kg/24 hours of aPCC for 24 hours or more; two of the eight were associated with thrombotic events and three of the eight were associated with TMA (Table 9). No TMA or thrombotic events were associated with the remaining instances of aPCC treatment. Of all instances of aPCC treatment, 67.1% consisted of only one infusion < 100 U/kg. (See Table 9.)

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Injection site reactions: Injection site reactions (ISRs) were reported very commonly from clinical trials. All ISRs observed in the Hemlibra clinical trials were reported as being non-serious and generally mild to moderate in intensity. Most ISRs resolved without treatment. The most commonly reported ISR symptoms were injection site erythema (7.4 %), injection site pruritus (5.3%) and injection site pain (5.3%).
Paediatric population: The paediatric population studied comprises a total of 95 patients, of which 2 (2%) were infants (1 months to less than 2 years of age), 55 (58%) were children (from 2 to less than 12 years of age) and 38 (40%) were adolescents (from 12 to less than 18 years old).
The safety profile of Hemlibra was overall consistent between infants, children, adolescents, and adults.
Drug Interactions
No adequate or well-controlled drug-drug interaction studies have been conducted with emicizumab.
Clinical experience indicates a drug interaction exists with emicizumab and aPCC (see Precautions and Adverse Reactions).
There is a possibility for hypercoagulability with rFVIIa or FVIII with emicizumab based on preclinical experiments. Emicizumab increases coagulation potential, therefore the coagulation factor dose required to achieve hemostasis may be lower than when used without Hemlibra prophylaxis.
Experience with concomitant administration of anti-fibrinolytics with aPCC or rFVIIa in patients receiving emicizumab prophylaxis is limited. However, the possibility of thrombotic events should be considered when systemic anti-fibrinolytics are used in combination with aPCC or rFVIIa in patients receiving emicizumab.
Caution For Usage
Instructions for Use: The patient must read, understand and follow the Instructions for Use before injecting HEMLIBRA. The healthcare provider should show the patient how to prepare, measure, and inject HEMLIBRA properly before using it for the first time. Ask the healthcare provider if the patient has any questions.
Important Information: Do not inject by self or someone else unless the patient has been shown how to by the healthcare provider.
Make sure the name HEMLIBRA appears on the box and vial label.
Before opening the vial, read the vial label to make sure the patient has the medicine strength(s) needed to give the dose prescribed. The patient may need to use more than 1 vial to give the correct dose.
Check the expiry date on the box and vial label. Do not use if the expiry date has passed.
Only use the vial once. After injecting the dose, throw away any unused HEMLIBRA left in the vial. Do not save unused medicine in the vial for later use.
Only use the syringes, transfer needles, and injection needles that the healthcare provider prescribes.
Only use the syringes, transfer needles and injection needles only once. Throw away any used syringes and needles.
If the prescribed dose is more than 2 mL, the patient will need to have more than one subcutaneous injection of HEMLIBRA; contact the healthcare provider for the injection instructions.
The patient must inject HEMLIBRA only under the skin.
Storing HEMLIBRA vials, needles and syringes: Keep the vial in the original box to protect the medicine from light. Store the vial in the refrigerator.
Do not freeze.
Do not shake the vial.
Take the vial out of the refrigerator 15 minutes before use and allow it to reach room temperature (below 30°C) before preparing an injection.
Once removed from the refrigerator, the unopened vial can be kept at room temperature for up to 7 days. After storage at room temperature unopened vials may be returned to the refrigerator. The total amount of time outside cold storage and at room temperature should not exceed 7 days.
Discard vials that have been kept at room temperature for more than 7 days or have been in temperatures above 30°C.
Keep the transfer needle, injection needle and syringe dry.
Inspecting the medicine and the supplies: Collect all supplies listed as follows to prepare and give the injection.
Check the expiry date on the box, on the vial label and on the supplies listed as follows. Do not use if the expiry date has passed.
Do not use the vial if: the medicine is cloudy, hazy or colored; the medicine contains particles; the cap covering the stopper is missing.
Inspect the supplies for damage. Do not use if they appear damaged or if they have been dropped.
Place the supplies on a clean, well-lit flat work surface.
INCLUDED IN THE BOX: Vial containing the medicine.
HEMLIBRA Instructions for Use.
NOT INCLUDED IN THE BOX: Alcohol wipes: Note: If the patient needs to use more than 1 vial to inject the prescribed dose, the patient must use a new alcohol wipe for each vial.
Gauze.
Cotton Ball.
Syringe: Note: For injection amount up to 1 ml use a 1 ml syringe. For injection amount between 1 ml and 2 ml use a 2 or 3ml syringe.
18G Transfer Needle: Note: If the patient needs to use more than 1 vial to inject the prescribed dose, the patient must use a new transfer needle for each vial.
Do not use the transfer needle to inject medicine.
26G Injection Needle with safety shield: Do not use the injection needle to withdraw medicine from vial.
Sharps disposal container.
Get Ready: Before use, allow the vial(s) to reach room temperature for about 15 minutes on a clean flat surface away from direct sunlight.
Do not try to warm the vial by any other way.
Wash the hands well with soap and water.
Selecting and preparing an injection site: Clean the chosen injection site area using an alcohol wipe.
Let the skin dry for about 10 seconds. Do not touch, fan or blow on the cleaned area before the injection.
For injection, the patient can use the: Thigh (front and middle).
Stomach area (abdomen), except for 5cm around the navel (belly button).
Outer area of the upper arm (only if a caregiver is giving the injection).
The patient should use a different injection site for each injection, at least 2.5cm away from the area used for the previous injection.
Do not inject into areas that could be irritated by a belt or waistband. Do not inject into moles, scars, bruises, or areas where the skin is tender, red, hard or the skin is broken.
Preparing the syringe for injection: Do not touch exposed needles or place them on a surface once the cap has been removed.
Once the syringe has been filled with the medicine, the injection must be given immediately.
Once the injection needle cap has been removed, the medicine in the syringe must be injected under the skin within 5 minutes. Do not use the syringe if the needle touches any surface.
Throw away any used vial(s), needles, vial or injection needle caps and used syringes in a sharps or puncture-proof container.
Important information after the injection: Do not rub the injection site after an injection.
If the patient sees drops of blood at the injection site, press a sterile cotton ball or gauze over the injection site for at least 10 seconds, until bleeding has stopped.
If the patient has bruising (small area of bleeding under the skin), an ice pack can also be pressed gently on the site. If bleeding does not stop, please contact the healthcare provider.
Disposing of the medicine and supplies: Important: Always keep the sharps disposal container out of reach of children.
Put the used needles and syringes in a sharps disposal container straight away after use. Do not throw away any loose needles and syringes in the household waste.
If the patient does not have a sharps disposal container, the patient may use a household container that is: made of heavy-duty plastic; can be closed with a tight-fitting, puncture resistant lid, without sharps being able to come out; upright and stable during use; leak-resistant; properly labeled to warn of hazardous waste inside the container.
When the sharps disposal container is almost full, the patient will need to follow the local guidelines for the right way to dispose of the sharps disposal container.
Do not throw away any used sharps disposal container in the household waste unless the local guidelines permit this. Do not recycle the used sharps disposal container.
1. PREPARATION: Step 1. Remove vial cap and clean top: Take the cap off the vial(s).
Throw away the vial cap(s) into the sharps disposal container.
Clean the top of the vial(s) stopper with an alcohol wipe.
Step 2. Attach transfer needle to syringe: Push and twist the transfer needle clockwise on to the syringe until it is fully attached.
Slowly pull back on the plunger and draw air into the syringe that is the same amount as the prescribed dose.
Step 3. Uncap transfer needle: Hold the syringe by the barrel with the transfer needle pointing up.
Carefully pull the transfer needle cap straight off and away from the body. Do not throw the cap away. Place the transfer needle cap down on a clean flat surface. The patient will need to recap the transfer needle after transferring the medicine.
Do not touch the needle tip or place it on a surface after the needle cap has been removed.
Step 4. Inject air into vial: Keep the vial on the flat working surface and insert the transfer needle and syringe straight down into the center of the vial stopper.
Keep the needle in the vial and turn the vial upside down.
With the needle pointing upwards, push on the plunger to inject the air from the syringe above the medicine.
Keep the finger pressed down on the syringe plunger.
Do not inject air into the medicine as this could create air bubbles in the medicine.
Step 5. Transfer medicine to syringe: Slide the tip of the needle down so that it is within the medicine.
Slowly pull back the plunger to fill the syringe with more than the amount of medicine needed for the prescribed dose.
Be careful not to pull the plunger out of the syringe.
Important: If the prescribed dose is more than the amount of medicine in the vial, withdraw all of the medicine and go to Combining Vials as follows now.
Step 6. Remove air bubbles: Keep the needle in the vial and check the syringe for larger air bubbles. Large air bubble can reduce the dose received.
Remove the larger air bubbles by gently tapping the syringe barrel with the fingers until the air bubbles rise to the top of the syringe. Move the tip of the needle above the medicine and slowly push the plunger up to push the air bubbles out of the syringe.
If the amount of medicine in the syringe is now at or below the prescribed dose, move the tip of the needle to within the medicine and slowly pull back the plunger until the patient has more than the amount of medicine needed for the prescribed dose.
Be careful not to pull the plunger out of the syringe.
Repeat the steps previously mentioned until the patient has removed the larger air bubbles.
Note: Ensure the patient has enough medicine in the syringe to complete the dose before moving onto the next step. If the patient cannot remove all the drug, turn the vial upright to reach the remaining amount.
Do not use the transfer needle to inject medicine as this may cause pain and bleeding.
2. INJECTION: Step 7. Recap transfer needle: Remove the syringe and transfer needle from the vial.
Using one hand, slide the transfer needle into the cap and scoop upwards to cover the needle.
Once the needle is covered, push the transfer needle cap towards the syringe to fully attach it with one hand to prevent accidentally sticking the patient with the needle.
Step 8. Clean injection site: Select and clean the injection site with an alcohol wipe.
Step 9. Remove transfer needle: Remove the transfer needle from the syringe by twisting anticlockwise and gently pulling.
Throw away the used transfer needle into a sharps disposal container.
Step 10. Attach injection needle to syringe: Push and twist the injection needle clockwise onto the syringe until it is fully attached.
Step 11. Move safety shield: Move the safety shield away from the needle and towards the syringe barrel.
Step 12. Uncap injection needle: Carefully pull the injection needle cap straightaway from the syringe.
Throw away the cap into a sharps disposal container.
Do not touch the needle tip or allow it to touch any surface.
After the injection needle cap has been removed, the medicine in the syringe must be injected within 5 minutes.
Step 13. Adjust plunger to prescribed dose: Hold the syringe with the needle pointing up and slowly push the plunger to the prescribed dose.
Check the dose, ensure the top rim of the plunger is in line with the mark on the syringe for the prescribed dose.
Step 14. Subcutaneous (under the skin) injection: Pinch the selected injection site and fully insert the needle at a 45° to 90° angle with a quick, firm action. Do not hold or push on the plunger while inserting the needle.
Hold the position of the syringe and let go of the pinched injection site.
Step 15. Inject the medicine: Slowly inject all of the medicine by gently pushing the plunger all the way down.
Remove the needle and syringe from the injection site at the same angle as inserted.
3. DISPOSAL: Step 16. Cover needle with safety shield.
Move the safety shield forward 90°, away from the syringe barrel.
Holding the syringe with one hand, press the safety shield down against a flat surface with a firm, quick motion until the patient hears a "click".
If the patient does not hear a click, look to see that the needle is fully covered by the safety shield.
Keep the fingers behind the safety shield and away from the needle at all times.
Do not detach injection needle.
Step 17. Throw away the syringe and needle: Put the used needles and syringes in a sharps disposal container right away after use. For further information refer to the "Disposing of the medicine and supplies" as previously mentioned.
Do not try to remove the used injection needle from the used syringe.
Do not recap the injection needle with the cap.
Important: Always keep the sharps disposal container out of reach of children.
Throw away any used caps, vial(s), needles and syringes in a sharps or puncture-proof container.
Combining Vials: If the patient needs to use more than 1 vial to get to the total prescribed dose, follow these steps after having drawn up the medicine from the first vial: Step A. Recap transfer needle: Remove the syringe and transfer needle from the first vial.
Using one hand, slide the transfer needle into the cap and scoop upwards to cover the needle.
Once the needle is covered, push the transfer needle cap toward the syringe to fully attach it with one hand to prevent accidentally sticking the patient with the needle.
Step B. Remove transfer needle: Remove the transfer needle from the syringe by twisting anticlockwise and gently pulling.
Throw away the used transfer needle into a sharps disposal container.
Step C. Attach a new transfer needle to syringe: Note: Use a new transfer needle each time the patient withdraws medicine from a new vial.
Push and twist a new transfer needle clockwise on to the syringe until it is fully attached.
Slowly pull back the plunger and draw some air into the syringe.
Step D. Uncap transfer needle: Hold the syringe by the barrel with the transfer needle cap pointing up.
Carefully pull the transfer needle cap straight off and away from the body. Do not throw the cap away. The patient will need to recap the transfer needle after drawing up the medicine.
Do not touch the needle tip.
Step E. Inject air into vial: With the new vial on the flat working surface, insert the new transfer needle and syringe, straight down into the center of the vial stopper.
Keep the transfer needle in the vial and turn the vial upside down.
With the needle pointing upwards, inject the air from the syringe above the medicine.
Keep the finger pressed down on the syringe plunger.
Do not inject air into the medicine as this could create air bubbles in the medicine.
Step F. Transfer medicine to syringe: Slide the tip of the needle down so that it is within the medicine.
Slowly pull back the plunger to fill the syringe barrel more that the amount of medicine needed for the prescribed dose.
Be careful not to pull the plunger out of the syringe.
Note: Ensure the patient has enough medicine in the syringe to complete the dose before moving onto the next step. If the patient cannot remove all the drug, turn the vial upright to reach the remaining amount.
Do not use the transfer needle to inject medicine as this may cause harm such as pain and bleeding.
Repeat steps A to F with each additional vial until the patient has more than the prescribed dose. Once completed, keep the transfer needle inserted in the vial and return to Step 6. Continue with the remaining steps.
Special precautions for disposal and other handling: Hemlibra solution is a sterile, preservative-free, and ready to use solution for subcutaneous injection that does not need to be diluted.
Hemlibra should be inspected visually to ensure there is no particulate matter or discolouration prior to administration. Hemlibra is a colourless to slightly yellow solution. The solution should be discarded if particulate matter is visible or product is discoloured.
Do not shake.
Hemlibra solution for injection vials are for single-use only.
A syringe, a transfer needle (or vial adapter) and an injection needle are needed to withdraw Hemlibra solution from the vial and inject it subcutaneously (please see recommended features as follows).
A 1 mL syringe should be used for an injection up to 1 mL of Hemlibra solution, whereas a 2 to 3 mL syringe should be used for an injection greater than 1 mL and up to 2 mL.
Refer to the Hemlibra "Instructions for Use" as previously mentioned for handling instructions when combining vials in a syringe. Different Hemlibra vial concentrations (30 mg/mL and 150 mg/mL) should not be used when combining vials to administer the prescribed dose.
1 mL syringe: Criteria: Transparent polypropylene or polycarbonate syringe with Luer-lock tip, graduation 0.01 mL.
When used together with a vial adapter, a low dead space plunger 1 mL syringe (transparent polypropylene or polycarbonate syringe with Luer-lock tip, graduation 0.01 mL) must be used.
2 to 3 mL syringe: Criteria: Transparent polypropylene or polycarbonate syringe with Luer-lock tip, graduation 0.1 mL.
When used together with a vial adapter, a low dead space plunger 3 mL syringe (transparent polypropylene or polycarbonate syringe with Luer-lock tip, graduation 0.1 mL) must be used.
Transfer needle or vial adapter: Criteria for transfer needle: Stainless steel with Luer-lock connection, gauge 18 G, length 35mm (1½"), preferably semi-blunted tip.
Criteria for vial adapter: Polycarbonate with Luer-lock connection, sterile, fitting 15 mm vial neck outer diameter, single-use, latex-free and non-pyrogenic.
Injection needle: Criteria: Stainless steel with Luer-lock connection, gauge 26 G, length preferably 9 mm (3/8") or maximally 13mm (½"), preferably including needle safety feature.
Please see Dosage & Administration and package leaflet (Instructions for Use), for additional information on administration.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Incompatibilities: No incompatibilities between Hemlibra and polypropylene or polycarbonate syringes, polycarbonate vial adapters and stainless steel needles have been observed.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Storage
Store in a refrigerator (2°C to 8°C).
Do not freeze.
Keep the vial in the outer carton in order to protect from light.
For storage conditions after first opening of the medicinal product, see Shelf-Life as follows.
Shelf-Life: Unopened vial: 30 months.
Once removed from the refrigerator, unopened vials can be kept at room temperature (below 30°C) for up to 7 days.
After storage at room temperature, unopened vials may be returned to the refrigerator. If stored out of and then returned to refrigeration, the total combined time out of refrigeration should not exceed 7 days. The vials should never be exposed to temperatures above 30 °C. Vials that have been kept at room temperature for more than 7 days or exposed to temperatures above 30 °C should be discarded.
Pierced vial and filled syringe: From a microbiological point of view, once transferred from the vial to the syringe, the medicinal product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.
MIMS Class
ATC Classification
B02BX06 - emicizumab ; Belongs to the class of other systemic hemostatics. Used in the treatment of hemorrhage.
Presentation/Packing
Soln for inj (colourless to slightly yellow solution in vial) 30 mg/mL x 1's. 60 mg/0.4 mL x 1's. 105 mg/0.7 mL x 1's. 150 mg/mL x 1's.
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