Tenecteplase (TNK) dosing calculator in ischaemic stroke

Clinical background

In acute ischaemic stroke within 4.5 hours of symptom onset, intravenous thrombolysis is a cornerstone of treatment. Alteplase, long the standard, is given as a bolus followed by an hour-long infusion, which is logistically burdensome, particularly during interhospital transfer for endovascular thrombectomy. Tenecteplase is a genetically modified variant of tissue plasminogen activator with 14-fold greater fibrin specificity, 80-fold greater resistance to PAI-1 and a longer half-life, which allows it to be given as a single intravenous bolus [2]. The dose in stroke differs from that in STEMI (0.5 mg/kg) and has been established through a series of dose-comparison studies in which 0.25 mg/kg proved to give the best balance of efficacy and safety.

Calculating the tenecteplase dose in ischaemic stroke

The dose is calculated from the patient's body weight:

$$\text{Dose} = 0{.}25 \times \text{Weight} \quad (\text{mg, intravenous bolus, max 25 mg})$$

where the weight is given in kilograms and the result is rounded to the nearest whole milligram. The calculator accepts weights between 30 and 200 kg. At a weight of 100 kg or more the ceiling of 25 mg is reached, and no further dose is given.

The dose of 0.25 mg/kg derives from EXTEND-IA TNK Part 1, an Australian multicentre study published in 2018 [1]. In this phase 2 trial, 202 patients with ischaemic stroke and angiographically confirmed occlusion of the internal carotid artery, the middle cerebral artery or the basilar artery, who were candidates for endovascular thrombectomy, were randomised to tenecteplase 0.25 mg/kg (max 25 mg) or alteplase 0.9 mg/kg (max 90 mg) within 4.5 hours of symptom onset. The primary outcome was reperfusion of more than 50 per cent of the ischaemic territory or the absence of retrievable thrombus at initial angiography. Tenecteplase was superior to alteplase both for reperfusion (22 per cent versus 10 per cent, P = 0.002 for non-inferiority, P = 0.03 for superiority) and for 90-day functional outcome (median mRS 2 versus 3, common OR 1.7, P = 0.04). Symptomatic intracerebral haemorrhage occurred in 1 per cent of both groups [1].

The choice of 0.25 mg/kg rather than a higher dose rests on several earlier dose-comparison studies. In the initial dose-escalation study by Haley and co-workers, 0.5 mg/kg was stopped after symptomatic intracranial haemorrhage in 2 of 13 patients [2]. In the TNK-S2B study, 0.4 mg/kg was eliminated as inferior because of a higher rate of sICH (3 of 19 patients) [2]. In the TAAIS study (Parsons 2012), 0.25 mg/kg was superior to 0.1 mg/kg for early recanalisation and 90-day outcome [2]. EXTEND-IA TNK Part 2 subsequently randomised 300 patients with large-vessel occlusion to 0.25 mg/kg or 0.4 mg/kg before thrombectomy and found identical reperfusion rates (19.3 per cent in both groups) but more sICH in the higher-dose group (7 versus 2), leading the authors to conclude that the higher dose confers no clinical advantage [2].

Interpretation in practice

The calculator gives a single dose administered as an intravenous bolus over 5 to 10 seconds, with no subsequent infusion. This is the central practical difference from alteplase, which requires a bolus of 10 per cent of the total dose followed by an hour-long infusion.

The ceiling dose of 25 mg applies at any weight above 100 kg. There is no reason to exceed it, since higher doses have not shown better efficacy and may increase the risk of bleeding [2].

Validation and performance

The largest and most representative validation of the 0.25 mg/kg dose to date is ATTEST-2, a UK multicentre study published in 2024 [3]. In this open, pragmatic trial with masked outcome assessment, 1,777 thrombolysis-eligible patients (modified intention-to-treat population) were randomised to tenecteplase 0.25 mg/kg or alteplase 0.9 mg/kg within 4.5 hours. The median baseline NIHSS was 7 (IQR 5 to 13) and the mean age 70.4 years, reflecting a broad stroke population not restricted to large-vessel occlusion. Tenecteplase was non-inferior to alteplase for the 90-day mRS distribution (OR 1.07, 95 per cent CI 0.90 to 1.27, P < 0.0001 for non-inferiority) but not superior (P = 0.43). Mortality was 8 per cent in both groups and sICH occurred in 2 per cent of both groups [3].

A meta-analysis from 2025 including 13 randomised trials with a total of 9,053 patients found that tenecteplase 0.25 mg/kg was significantly better than alteplase for an excellent functional outcome (mRS 0 to 1 at 90 days; RR 1.06, 95 per cent CI 1.01 to 1.10, P = 0.01) with no difference in mortality [4]. Subgroup analyses showed that neither 0.1 mg/kg nor 0.4 mg/kg conferred any advantage over alteplase, leading the authors to conclude that 0.25 mg/kg is the optimal dose [4].

An earlier qualitative synthesis of the first five randomised trials (1,585 patients) found tenecteplase superior for recanalisation in large-vessel occlusion and non-inferior for functional outcome at 3 months, with no increase in sICH or mortality [2].

Limitations

The calculator applies to adult patients with acute ischaemic stroke within 4.5 hours of symptom onset or of the time last known well. It should not be used in children, and dosing at weights below 30 kg has not been studied in stroke.

EXTEND-IA TNK Part 1, the primary derivation study, included only patients with angiographically confirmed large-vessel occlusion who were candidates for thrombectomy [1]. ATTEST-2, by contrast, included a broader population of thrombolysis-eligible patients regardless of vessel status and confirmed non-inferiority in this more representative cohort [3]. The dose can therefore be applied both in patients with and without confirmed large-vessel occlusion.

Tenecteplase in stroke remains off-label in many countries, including the USA, where the FDA has not approved the indication. The 2021 ESO guidelines recommend alteplase as first-line treatment and state that the evidence for tenecteplase was at that time insufficient for a strong recommendation, but note that ongoing trials were expected to clarify its role [5]. With ATTEST-2 and later meta-analyses the evidence has strengthened considerably, and several national guidelines have since been updated to recommend tenecteplase as an alternative to alteplase [3,4].

The commonest contraindications are the same as for alteplase: active bleeding, a history of intracranial haemorrhage, recent major surgery, and coagulation disorders. The calculator does not handle these contraindications and presupposes that the clinician has already assessed eligibility for thrombolysis.

References

1. Campbell BCV, Mitchell PJ, Churilov L, et al. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med 2018;378(17):1573-1582. PMID: 29694815
2. Warach SJ, Dula AN, Milling TJ Jr. Tenecteplase Thrombolysis for Acute Ischemic Stroke. Stroke 2020;51(11):3440-3451. PMID: 33045929
3. Muir KW, Ford GA, Ford I, et al. Tenecteplase versus alteplase for acute stroke within 4·5 h of onset (ATTEST-2): a randomised, parallel group, open-label trial. Lancet Neurol 2024;23(11):1087-1096. PMID: 39424558
4. Hagag AM, Kormod ME, Ads ME, et al. Tenecteplase versus alteplase in patients with acute ischemic stroke: an updated systematic review and meta-analysis. Eur J Med Res 2025;30:726. PMID: 40775658
5. Berge E, Whiteley W, Audebert H, et al. European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke. Eur Stroke J 2021;6(1):I-LXII. PMID: 33817340