safety profile
Metalyse 25 mg is now available for adults for thrombolytic treatment of acute ischaemic stroke within 4.5 hours from last known well and after exclusion of intracranial haemorrhage1
Because Every
Minute Matters
In the AcT phase III clinical trial, no difference in safety profile was observed with tenecteplase* compared to alteplase for the treatment of AIS.†2
In AcT, the risk of key adverse events including death within 90 days and symptomatic intracerebral haemorrhage was similar for tenecteplase compared to alteplase. Tenecteplase was also similar to alteplase in the rate of additional safety outcomes, including haemorrhagic infarction and intracranial, subarachnoid and intraventricular haemorrhage.2
This figure is made by Boehringer Ingelheim based on ref. Menon BK, et al. Lancet 2022; 400:161-169.
AcT was a multicenter, open-label, parallel-group, registry-linked, RCT, in which 1600 patients were enrolled from 22 primary and comprehensive stroke centres across Canada and randomly assigned to tenecteplase (as a weight-tiered bolus dose, based on 0.25 mg/kg, to a maximum of 25 mg, n=816) or alteplase (0.9 mg/kg to a maximum of 90 mg, n=784). Patients 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4.5 hrs of symptom onset, and eligible for thrombolysis per Canadian guidelines, were included. The primary outcome in AcT was a mRS score of 0-1 at 90-120 days after treatment, assessed via blinded review in the ITT population.2
This table is made by Boehringer Ingelheim based on ref. Burgos A. M. and Saver J. L. Stroke 2019; 50:2156-2162. (Supplement) Nor-Test is not included because it only tested Tenecteplase 0.4mg.
A meta-analysis of 5 RCTs also showed similar safety outcomes for tenecteplase vs alteplase in the treatment of AIS.‡3
In patients receiving tenecteplase 0.25 mg/kg, the meta-analysis showed similar key safety endpoints for tenecteplase compared to alteplase.
A systematic literature search and formal meta-analysis were conducted per PRISMA guidelines, adapted to noninferiority analysis. The primary outcome was freedom from disability (mRS score, 0–1) at 3-months, and additional efficacy and safety outcomes were analysed. The systematic search identified 5 trials enrolling 1585 patients (tenecteplase=828, alteplase=757). All alteplase patients received standard 0.9 mg/kg dosing, while tenecteplase dosing was 0.1 mg/kg in 6.8%, 0.25 mg/kg in 24.6%, and 0.4 mg/kg in 68.6% of participants.3
Frequency of adverse reactions
| System Organ Class | Adverse reaction Frequency |
|---|---|
| Immune system disorders | |
| Rare | Anaphylactoid reaction (including rash, urticaria, bronchospasm, laryngeal oedema) |
| Nervous system disorders | |
| Uncommon | Intracranial haemorrhage (such as cerebral haemorrhage, cerebral haematoma, haemorrhagic stroke, haemorrhagic transformation stroke, intracranial haematoma, subarachnoid haemorrhage) including associated symptoms as somnolence, aphasia, hemiparesis, convulsion |
| Eye disorders | |
| Uncommon | Eye haemorrhage |
| Cardiac disorders | |
| Uncommon | Reperfusion arrhythmias (such as asystole, accelerated idioventricular arrhythmia, arrhythmia, extrasystoles, atrial fibrillation, atrioventricular first degree to atrioventricular block complete, bradycardia, tachycardia, ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia) occur in close temporal relationship to treatment with tenecteplase. |
| Rare | Pericardial haemorrhage |
| Vascular disorders | |
| Very common | Haemorrhage |
Rare | Embolism (thrombotic embolisation) |
| Respiratory, thoracic and mediastinal disorders | |
| Common | Epistaxis |
Rare | Pulmonary haemorrhage |
Gastrointestinal disorders | |
| Common | Gastrointestinal haemorrhage (such as gastric haemorrhage, gastric ulcer haemorrhage, rectal haemorrhage, haematemesis, melaena, mouth haemorrhage) |
Uncommon | Retroperitoneal haemorrhage (such as retroperitoneal haematoma) |
Not known | Nausea, vomiting |
Skin and subcutaneous tissue disorders | |
Common | Ecchymosis |
| Renal and urinary disorders | |
Common | Urogenital haemorrhage (such as haematuria, haemorrhage urinary tract) |
| General disorders and administration site conditions | |
Common | Injection site haemorrhage, puncture site haemorrhage |
| Investigations | |
| Rare | Blood pressure decreased |
Not known | Body temperature increased |
| Injury, poisoning and procedural complications | |
| Not Known | Fat embolism, which may lead to corresponding consequences in the organs concerned |
Table is adapted from SmPC Frequency groupings are defined according to the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10000 to <1/1000), very rare (<1/10000), not known (cannot be estimated from the available data).
Footnotes
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*
Tenecteplase was administrated as a one-time decile-weight-tiered bolus dose, based on 0.25 mg/kg for the maximum weight at each tier: <60 kg, 15 mg tenecteplase; ≥60 to <70 kg, 17.5 mg; ≥70 to <80 kg, 20 mg; ≥80 to <90 kg, 22.5 mg; and ≥90 kg, 25 mg.2
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†
In the AcT phase III clinical trial, the rates of adverse events were similar for tenecteplase compared to alteplase. The main adverse events were: death within 90 days (15.3% for tenecteplase vs. 15.4% for alteplase; RD -0.1 [95% CI -3.7, 3.5]), symptomatic intracerebral haemorrhage (3.4% vs. 3.2%; RD 0.2 [95% CI -1.5, 2.0]), extracranial bleeding (0.8% vs. 0.8%; RD 0.0 [95% CI -0.9, 0.8]), and orolingual angio-oedema (1.1% vs. 1.2%; RD -0.1 [95% CI -1.1, 1.0]).2
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‡
The safety outcomes analysed were sICH and mortality. Symptomatic hemorrhage events in individual trials were identified using the sICH definition employed in each trial. For mortality and sICH, the noninferiority margins were set at 1%.
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AIS = Acute ischemic stroke, CI = Confidence Interval, RD = Risk Difference, sCIH = symptomatic intra cerebral hemorrhage.
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Fibrinolytic treatment of acute ischaemic stroke (within 4,5 hours of last know well and after exclusion of intracerebral haemorhage by suitable imaging technology)
References
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Metalyse® European Summary of Product Characteristics.12/2023
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Menon BK, et al. Lancet 2022; 400:161-169.
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Burgos A. M. and Saver J. L. Stroke 2019; 50:2156-2162.