Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Roche Products Ltd. Please contact Roche Drug Safety Centre by emailing welwyn.uk_dsc@roche.com or calling +44 (0)1707 367554.
HEMLIBRA delivers sustained protection with a consistent safety profile2
Roche/Chugai recognise the interest that the haemophilia community has around the long-term efficacy and safety of HEMLIBRA. We are committed to ensuring that healthcare professionals, patients and caregivers have the necessary information to make informed treatment decisions with HEMLIBRA.
Please find below published information on the benefit–risk profile of HEMLIBRA, including long-term safety data, and educational materials on post-marketing safety reporting and pharmacovigilance. These are available for healthcare professionals to access on this website.
Pharmacovigilance: information on accurate and timely reporting of safety data.
Links to publications discussing the efficacy and safety of HEMLIBRA in haemophilia A.
For details on the concomitant use of HEMLIBRA with other medications please refer to the
HEMLIBRA® Summary of Product Characteristics
The following risk minimisation materials
can be found at www.medicines.org.uk:
- Guide for healthcare professionals
- Guide for patients/caregivers
- Patient alert card
- Guide for laboratory professionals
For additional recent safety information, please refer to
Publications
Serious thrombotic events/thrombotic microangiopathy (TE/TMA) events were uncommon in the HAVEN studies1
Serious TE/TMA events occurred in patients receiving HEMLIBRA prophylaxis when on average a cumulative amount of >100 u/kg daily of activated prothrombin complex concentrate (aPCC) for 24 hours or more was administered1
Serious TE and TMA events occurred in 6.5% (2/31) and 9.7% (3/31) of patients, respectively, that received at least one dose of aPCC, while being treated with HEMLIBRA.1
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Characteristics of TE/TMA events
Four out of five patients improved within 1 month after HEMLIBRA interruption and aPCC discontinuation (n=373):3,4
- Two patients restarted HEMLIBRA
- One fatality due to rectal haemorrhage occurred, as the TMA event was resolving. Death was not attributed to HEMLIBRA5
Characteristics of serious TE/TMA events in the HAVEN 1 study1,4,6
Evidence of improvement was distinct from the usual clinical course observed in atypical haemolytic uremic syndrome and classic TMA events, such as thrombotic thrombocytopenic purpura.1
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Summary of TE/TMA events
Summary of TE/TMA events in all patients that had received HEMLIBRA up until 31 December 2019 (all events reported during and after clinical trials)7
*Events reported include off-label use of HEMLIBRA for patients with acquired haemophilia A (AHA). HEMLIBRA is only indicated in patients with congenital haemophilia A classified as severe or with Factor VIII inhibitors.
All non-aPCC-associated TEs occurred in patients with known co-morbidities or pre-existing risk factors:7,8
- Six cases of non-aPCC-associated myocardial infarction occurred in patients with known cardiovascular risk factors
- Two TEs were identified in the long-term follow-up of:2,9
- HAVEN 1, in a patient with non-serious device occlusion and a history of device-related thrombosis
- HAVEN 3, in a patient >65 years, with undiagnosed coronary artery disease
- HAVEN 1, in a patient with non-serious device occlusion and a history of device-related thrombosis
- In seven out of nine patients (two events occurred in one person) with non-device-related TEs, there was no reported change to HEMLIBRA prophylaxis as a result of the event
HEMLIBRA was generally well tolerated1
Summary of adverse drug reactions (ADRs) from pooled HAVEN clinical trials (n=373; phase III, median duration, 33 weeks)
Please refer to the SPC for the full list of ADRs.
- Three patients (0.8%) withdrew from treatment due to ADRs (TMA event, n=1; skin necrosis and superficial thrombophlebitis, n=1; headache, n=1)
- 95% of injection site reactions resolved without treatment
Safety considerations for patients receiving HEMLIBRA1
Clinical trial experience with HEMLIBRA indicated that:
- Concomitant use with FVIII and rFVIIa alone have not been associated with serious adverse events, including TE or TMA events
- A drug interaction exists with HEMLIBRA and aPCC
Avoid aPCC with HEMLIBRA, unless no other treatment options are available.
For more details on the concomitant use of HEMLIBRA with other medications please refer to the
HEMLIBRA® Summary of Product Characteristics
The following risk minimisation materials
can be found at www.medicines.org.uk:
- Guide for healthcare professionals
- Guide for patients/caregivers
- Patient alert card
- Guide for laboratory professionals
HEMLIBRA increases a patient’s coagulation potential1
If administering systemic haemostatic agents with HEMLIBRA:
- Hypercoagulability is possible, based on preclinical experiments
- Dose required to achieve haemostasis may be lower than when used without HEMLIBRA
Considerations for concomitant use with:
-
Factor VIII (FVIII)¹
Clinical experience indicated that concomitant FVIII use has not been associated with serious AEs1
Most breakthrough bleeds were treated with FVIII <50 u/kg/day for <24 hours (HAVEN 3)10
Percentages based on 215 treatment events, in 64 patients.
*A treatment event started with the first FVIII treatment and included all infusions up to 36 hrs. Treatment events included administration of FVIII to treat a bleed and preventative doses given before a medical procedure or activity.
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Bypassing agents (BPAs)¹
Treatment with BPAs should be discontinued the day before initiating HEMLIBRA prophylaxis
If BPAs are needed during HEMLIBRA prophylaxis:
- Dose and duration will depend on the patient’s clinical condition, the location and extent of bleeding
- Dose may be lower than that used without HEMLIBRA prophylaxis
- BPA dosing guidance should be followed for at least 6 months, following discontinuation of HEMLIBRA prophylaxis
Please refer to the SPC for further information about special warnings and precautions, guidance on concomitant use of HEMLIBRA with BPAs, and the full list of adverse events.
Clinical experience indicated that concomitant rFVIIa use has not been associated with serious adverse events
No TE/TMA events were observed in clinical trials, in patients receiving rFVIIa alone with HEMLIBRA.
-
Activated prothrombin complex concentrate (aPCC)¹
Clinical experience has indicated that a drug interaction exists with HEMLIBRA and aPCC
- Serious TE/TMA events were observed in patients receiving concomitant aPCC for treatment of a breakthrough bleed, in the HAVEN studies
- Events were reported in patients receiving HEMLIBRA when a cumulative dose of aPCC, averaging >100 u/kg/day for ≥24 hours was administered
Avoid aPCC with HEMLIBRA, unless no other treatment options are available
- If aPCC is indicated, the total dose should not exceed 100 u/kg in the first 24 hours of treatment
- Initial dose should not exceed 50 u/kg; additional doses should be administered under medical supervision, with laboratory monitoring recommended
- Weigh the risk of TE/TMA events when considering aPCC >100 u/kg in the first 24 hours
- If aPCC is administered with HEMLIBRA, monitor patients for TE/TMA events
Long-term safety2
Safety outcomes were consistent over time with HEMLIBRA prophylaxis, in the HAVEN 1–4 studies (median duration of treatment: 120 weeks; interquartile range 89–164).
The safety population only included those patients who received HEMLIBRA. One participant in HAVEN 1 discontinued prior to HEMLIBRA treatment and was excluded from the safety analyses.
*Assessed using clinical criteria for diagnosing anaphylaxis (Sampson HA et al. J Allergy Clin Immunol 2006;117:391-7) and includes all participants that experienced indicative symptoms.
**Of the two TEs not related to concomitant aPCC and HEMLIBRA, one TE was associated with device occlusion of a peripherally inserted central catheter and the other with a myocardial infarction.
▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Roche Products Ltd. Please contact Roche Drug Safety Centre by emailing welwyn.uk_dsc@roche.com or calling +44 (0)1707 367554. As HEMLIBRA® is a biological medicine, healthcare professionals should report adverse reactions by brand and batch number.
For full details please refer to the HEMLIBRA® Summary of Product Characteristics.
AE, adverse event; ADR, adverse drug reaction; AHA, acquired haemophilia A; aPCC, activated prothrombin complex concentrate; BPA, bypassing agent; FVIII, Factor VIII; MOA, mechanism of action; rFVIIa, activated recombinant Factor VII; SOC, system organ class; TE, thrombotic events; TMA, thrombotic microangiopathy.
References:
- HEMLIBRA SPC.
- Callaghan MU et al. ASH 2020:1800 [Poster Presentation].
- Oldenburg J et al. New Eng J Med 2017;377:809–18.
- Oldenburg J et al. New Eng J Med 2017;377:809–18 [Supplementary Appendix].
- Khoo L et al. Haemophilia 2020; DOI: 10.1111/hae.14110 (ePub ahead of print).
- Data on file. F. Hoffmann-La Roche. HEMI-2018-01.
- Lee L et al. EAHAD 2020 [Oral Presentation].
- Kruse-Jarres R & Hay CRM. N Eng J Med 2020;382:785.
- Callaghan MU et al. ASH 2020:1800 [Abstract].
- Mahlangu J et al. New Eng J Med 2018;379:811–22. [Supplementary Appendix].
M-GB-00004683
Date of preparation: September 2021
