Stroke tPA Dose
The recommended dose of tPA (alteplase) for acute ischemic stroke is 0.9 mg/kg with a maximum total dose of 90 mg, administered as 10% IV bolus over 1 minute followed by 90% infusion over 60 minutes. 1, 2
Standard Dosing Protocol
- Total dose: 0.9 mg/kg (maximum 90 mg) 1, 2
- Initial bolus: 10% of total calculated dose given IV over 1 minute 2, 3
- Remaining infusion: 90% of total dose infused over 60 minutes 2, 3
This dosing regimen is based on the landmark NINDS trial that demonstrated improved functional outcomes at 3 months when tPA was administered within 3 hours of symptom onset. 1
Time Window Considerations
The dosing remains the same regardless of time window, but eligibility criteria differ:
- 0-3 hours: Level A recommendation - Offer tPA to all patients meeting NINDS inclusion/exclusion criteria (absolute benefit: 12% more patients achieve minimal/no disability, NNT=8) 1, 3
- 3-4.5 hours: Level B recommendation - Consider tPA for carefully selected patients meeting ECASS III criteria (smaller benefit with NNT=14 for favorable outcome) 1, 3
- Beyond 4.5 hours: Contraindicated - Do not administer IV tPA (Grade 1B recommendation against use) 3, 4
Critical Dosing Considerations
Maximum dose cap is essential: The 90 mg maximum dose limit must be strictly observed. Patients weighing >100 kg receive a lower per-kilogram dose (0.82 mg/kg vs 0.90 mg/kg), but research supports maintaining this cap as patients >100 kg who received lower per-kilogram doses had higher rates of symptomatic ICH (2.6% vs 1.7%) and mortality despite similar functional outcomes. 5
Do not modify the dose: Lower doses (such as 0.6 mg/kg) studied in patients beyond 3 hours showed an 11% symptomatic hemorrhage rate with only 14% early major improvement, demonstrating that dose reduction does not improve the safety profile. 6
Safety Profile with Standard Dosing
- Baseline symptomatic ICH rate: 4-6% with proper dosing 2, 3
- NINDS trial data: 6.4% symptomatic ICH in tPA-treated patients versus 0.6% in placebo 2
- Patients on antiplatelet therapy: 3% absolute increased risk of symptomatic ICH but can still receive standard dosing 2, 3
Absolute Contraindications to Standard Dosing
Never administer tPA to patients on direct oral anticoagulants (DOACs) like apixaban due to substantially elevated bleeding risk. 2, 3
Administration Timing
Once the decision is made to administer tPA, treat as rapidly as possible within the appropriate time window, as earlier treatment results in greater proportional benefit. 1, 2, 3