Intravenous Alteplase (recombinant tissue plasminogen activator, or rtPA) remains a cornerstone of hyperacute stroke management. Accurate dosing is critical, as both under-dosing (reduced efficacy) and over-dosing (increased risk of hemorrhage) can significantly impact patient outcomes.

The following guide reflects current standards from the 2026 AHA/ASA Guidelines for the early management of acute ischemic stroke.

1. The Standard Dosing Regimen

The dose of Alteplase for acute ischemic stroke is strictly weight-based.

• Standard Dose: 0.9 mg/kg of actual body weight.
• Maximum Total Dose: 90 mg (for patients weighing $\ge$ 100 kg).

Administration Protocol

Alteplase must be administered using a “Bolus-then-Infusion” method:

1. Initial Bolus (10% of total dose): Administered as an intravenous manual push or rapid infusion over 1 minute.
2. Continuous Infusion (90% of total dose): Administered intravenously via an infusion pump over the following 60 minutes.

2. Preparation and Reconstitution

Alteplase is typically supplied as a lyophilized powder (usually 50 mg or 100 mg vials) that must be reconstituted before use.

• Diluent: Use only the provided Sterile Water for Injection (SWFI).
• Concentration: Reconstitute to a final concentration of 1 mg/mL.
• Mixing: Gently swirl or roll the vial. Do not shake, as this creates excessive foam and can denature the protein.
• Visual Check: The solution should be colorless to pale yellow. If it is cloudy or contains large particles, discard it.

3. Important Safety Thresholds

To ensure safe administration, certain clinical targets must be met before and during the dose:

Blood Pressure (BP) Targets

• Pre-administration: BP must be lowered to < 185/110 mmHg before the bolus starts.
• Post-administration: BP must be maintained $\le$ 180/105 mmHg for at least 24 hours following the infusion to prevent hemorrhagic transformation.

Weight Estimation

While actual weight is preferred, the 2026 guidelines acknowledge that in emergency settings, estimated weight can be used to avoid treatment delays, as “time is brain.”

4. Post-Infusion Monitoring

Once the 60-minute infusion is complete, the “tPA waste” (any remaining fluid in the tubing) must be flushed through with a 0.9% Sodium Chloride flush at the same rate to ensure the patient receives the full calculated dose.

• Neurological Checks: Perform NIH Stroke Scale (NIHSS) or equivalent checks every 15 minutes during the infusion and for 2 hours after.
• Antithrombotics: Do not administer aspirin, heparin, or other antiplatelet/anticoagulant drugs for 24 hours after Alteplase. A follow-up CT or MRI must be performed at 24 hours to rule out hemorrhage before starting these medications.

5. Alteplase vs. Tenecteplase (2026 Update)

The 2026 guidelines now recognize Tenecteplase (TNK) as a preferred alternative to Alteplase in many settings due to its simplified dosing:

• Tenecteplase Dose: 0.25 mg/kg (Max 25 mg) as a single 5-second bolus.
• Advantage: Eliminates the need for a 60-minute infusion pump, making it ideal for mobile stroke units and inter-facility transfers.

6. References and Clinical Links

Official Guidelines

• AHA/ASA 2026 Stroke Guidelines: 2026 Guideline for the Early Management of Acute Ischemic Stroke
• FDA Professional Label: Activase (Alteplase) Prescribing Information

Decision Tools

• MDCalc Alteplase Dosing: Alteplase Stroke Dosing Calculator
• StatPearls (NIH): Alteplase Pharmacology and Administration