What is the current dosing of TNK (tenecteplase) for acute ischemic stroke?

Current Dosing of Tenecteplase (TNK) for Acute Ischemic Stroke

The recommended dose of tenecteplase for acute ischemic stroke is 0.25 mg/kg (maximum 25 mg) administered as a single intravenous bolus. 1

Dosing Guidelines

The American Heart Association provides weight-based dosing recommendations:

• Weight < 60 kg: 30 mg
• Weight 60-69 kg: 35 mg
• Weight 70-79 kg: 40 mg
• Weight 80-89 kg: 45 mg
• Weight ≥ 90 kg: 50 mg

Alternatively, a single bolus intravenous injection with a dose of 0.25 mg/kg (maximum 25 mg) can be administered 1.

Evidence Supporting Current Dosing

The 0.25 mg/kg dose has emerged as the preferred dosing regimen based on recent evidence:

• Network meta-analyses have demonstrated that tenecteplase at 0.25 mg/kg provides superior efficacy compared to alteplase 0.9 mg/kg for excellent functional outcomes (OR, 1.16; 95% CrI, 1.01-1.33) 2
• The 0.25 mg/kg dose ranked first in efficacy outcomes in SUCRA analyses, while the 0.4 mg/kg dose ranked last 2
• Clinical trials comparing different doses (0.25 mg/kg vs. 0.4 mg/kg) have not demonstrated advantages of the higher dose 3

Clinical Context and Indications

Tenecteplase is particularly beneficial in specific clinical scenarios:

1. Patients requiring urgent transport to comprehensive stroke centers for endovascular therapy
2. Patients evaluated at comprehensive stroke centers who are eligible for endovascular intervention
3. Patients with mild neurological deficit and no significant intracranial occlusion 1

Administration Considerations

• Tenecteplase should be administered as quickly as possible after the decision to perform thrombolysis
• Unlike alteplase (which requires a 60-minute infusion), tenecteplase is given as a single IV bolus, making it more convenient in emergency settings 1, 3
• Patients should be transferred immediately to a center with percutaneous intervention capability after thrombolysis if endovascular therapy is indicated 1

Contraindications

Absolute contraindications include:

• Previous intracranial hemorrhage
• Known structural vascular cerebral lesion
• Known malignant intracranial neoplasm
• Ischemic stroke in the last 3 months
• Suspected aortic dissection
• Active bleeding or hemorrhagic diathesis
• Significant head or facial trauma in the last 3 months
• Intracranial or intra-spinal surgery in the last 2 months
• Uncontrolled severe hypertension (SBP >180 mmHg or DBP >110 mmHg) 1

Current Guideline Recommendations

The 2018 AHA/ASA guidelines state that tenecteplase at 0.4 mg/kg has not been proven superior or non-inferior to alteplase but might be considered as an alternative in patients with minor neurological impairment and no major intracranial occlusion (Class IIb, Level B-R) 4. However, more recent evidence and guidelines now favor the 0.25 mg/kg dose 1, 2.

Safety Profile

• Tenecteplase has a safety profile similar to alteplase with comparable rates of symptomatic intracranial hemorrhage 5, 3
• Recent large trials have shown symptomatic intracerebral hemorrhage rates of approximately 1.2% with tenecteplase, similar to alteplase 5

Clinical Pearls

• Tenecteplase offers several advantages over alteplase: higher fibrin specificity, longer half-life, and single-bolus administration 1, 3
• The convenience of bolus administration makes tenecteplase particularly valuable in "drip and ship" scenarios where patients need to be transferred for endovascular therapy 6
• While tenecteplase is increasingly used in clinical practice for stroke, it's important to note that regulatory approval specifically for stroke indication varies by country 6