Can tenecteplase be given at the pulmonary embolism dose (0.5 mg/kg) for treatment of both pulmonary embolism and acute ischemic stroke?

No, Tenecteplase Cannot Be Given at the PE Dose for Stroke

The dosing of tenecteplase differs critically between pulmonary embolism and acute ischemic stroke, and using the PE dose (0.5 mg/kg) for stroke would result in dangerous overdosing that doubles the recommended stroke dose and significantly increases hemorrhagic risk. 1, 2

Critical Dosing Differences

Stroke Dosing

• Tenecteplase for acute ischemic stroke is administered at 0.25 mg/kg (maximum 25 mg) as a single IV bolus 1, 3
• This dose has been validated in multiple trials and meta-analyses showing optimal efficacy and safety 4, 5
• The American Heart Association/American Stroke Association suggests tenecteplase at this dose as an alternative to alteplase (Class IIb, Level of Evidence B-R) 1, 2

PE Dosing

• Tenecteplase for myocardial infarction (and by extension PE in some protocols) uses 0.5 mg/kg dosing 5
• For PE, intraprocedural pulse delivery uses much lower absolute doses (5-10 mg) when combined with catheter-directed therapy 6
• The PEITHO trial used tenecteplase for intermediate-risk PE but did not specify using the 0.5 mg/kg MI dose 6

Why This Distinction Matters

Safety Concerns with Higher Dosing

• Using 0.5 mg/kg (PE dose) instead of 0.25 mg/kg (stroke dose) would double the thrombolytic exposure in stroke patients 1, 5
• Studies comparing different tenecteplase doses in stroke found no advantage to the higher 0.4 mg/kg dose over 0.25 mg/kg, and the 0.4 mg/kg dose ranked last in efficacy outcomes 4
• The absolute increase in symptomatic intracranial hemorrhage with thrombolysis is already approximately 6% at the correct stroke dose 3
• Real-world data shows tenecteplase 0.25 mg/kg has lower odds of symptomatic ICH compared to alteplase (aOR 0.42,95% CI 0.30-0.58) 7

Evidence Supporting 0.25 mg/kg for Stroke

• Network meta-analysis demonstrated tenecteplase 0.25 mg/kg was superior to alteplase 0.9 mg/kg for excellent functional outcomes (OR 1.16,95% CI 1.01-1.33) 4
• The 0.25 mg/kg dose ranked first in SUCRA analysis for efficacy outcomes 4
• This dose shows superior recanalization rates (22% vs 10% substantial reperfusion compared to alteplase) in large vessel occlusions 2

Common Pitfall to Avoid

Clinicians must be extremely careful not to confuse the myocardial infarction dosing protocol (0.5 mg/kg) with the stroke dosing protocol (0.25 mg/kg) 2. This is a critical medication safety issue, as:

• Both conditions may present in emergency settings where rapid decision-making is required
• The same drug name is used for different indications with different doses
• Doubling the dose would expose stroke patients to unnecessary hemorrhagic risk without demonstrated benefit
• The single-bolus administration makes dose correction impossible once given 1, 3

Administration Specifics for Stroke

• Treatment should be initiated within 4.5 hours of symptom onset 3, 8
• Administer as a single IV bolus at 0.25 mg/kg with a maximum dose of 25 mg 1, 3
• Target door-to-needle time of less than 60 minutes 2
• Both tenecteplase and alteplase share similar contraindications including intracranial hemorrhage, recent significant trauma or surgery, and uncontrolled hypertension 1, 3