Hemlibra

Hemlibra Special Precautions

emicizumab

Manufacturer:

Roche

Distributor:

Zuellig Pharma
Full Prescribing Info
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 12). 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 12 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 12.)

Click on icon to see table/diagram/image

Effects on ability to drive and use machines: Hemlibra has no influence on the ability to drive and use machines.
Use in Childen: 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).
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in