What is the recommended dose of injectable tissue‑type plasminogen activator (alteplase) for an adult with an acute ischemic event (stroke, myocardial infarction, or pulmonary embolism)?

Injectable Alteplase Dosing

Acute Ischemic Stroke

For acute ischemic stroke, administer alteplase at 0.9 mg/kg (maximum 90 mg total) with 10% given as an IV bolus over 1 minute, followed by 90% infused over 60 minutes. 1, 2

Dosing Calculation

• Total dose: 0.9 mg/kg body weight (absolute maximum 90 mg regardless of weight) 1, 2
• Initial bolus: 10% of total dose (0.09 mg/kg) administered IV push over exactly 1 minute 1, 2
• Continuous infusion: 90% of total dose (0.81 mg/kg) administered over 60 minutes 1, 2

Time Window Considerations

• 0-3 hours: Standard dosing applies with NINDS inclusion/exclusion criteria 1
• 3-4.5 hours: Same 0.9 mg/kg dosing, but with additional exclusion criteria (age >80 years, oral anticoagulant use regardless of INR, NIHSS >25, or history of both stroke and diabetes) 1, 2
• Beyond 4.5 hours: Not recommended based on current evidence 3

Critical Safety Points

• Blood pressure must be reduced below 185/110 mmHg before initiating thrombolysis 2
• Only blood glucose assessment is required before administration—do not delay for other laboratory results 2
• Target door-to-needle time <60 minutes in 90% of patients, with optimal median of 30 minutes 2

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Acute Myocardial Infarction

For acute MI, use the accelerated regimen: 15 mg IV bolus, followed by 0.75 mg/kg over 30 minutes (maximum 50 mg), then 0.5 mg/kg over 60 minutes (maximum 35 mg). 4

Dosing Protocol

• Initial bolus: 15 mg IV push 4
• First infusion: 0.75 mg/kg over 30 minutes (maximum 50 mg) 4
• Second infusion: 0.5 mg/kg over 60 minutes (maximum 35 mg) 4
• Total maximum dose: 100 mg 4

Required Adjunctive Therapy

• Aspirin 150-300 mg orally or 80-150 mg IV must be given concurrently 4
• Clopidogrel 600 mg loading dose orally 4
• Anticoagulation with enoxaparin IV followed by subcutaneous dosing or weight-adjusted unfractionated heparin 4

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Acute Massive Pulmonary Embolism

For massive PE with hemodynamic instability, administer 50 mg alteplase IV in cardiac arrest or deteriorating patients, or 100 mg over 90 minutes in stable patients with confirmed massive PE. 1

Dosing by Clinical Scenario

• Cardiac arrest: 50 mg IV bolus, reassess at 30 minutes 1
• Deteriorating patient: 50 mg IV bolus 1
• Stable but confirmed massive PE: 100 mg over 90 minutes (accelerated MI regimen) 1

Follow-up Anticoagulation

• Unfractionated heparin initiated 3 hours after thrombolysis, preferably weight-adjusted 1

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Critical Pitfall to Avoid

Never confuse stroke and MI dosing protocols—this is a potentially fatal error. 2, 4, 5 The stroke protocol (0.9 mg/kg, max 90 mg) and MI protocol (15 mg bolus + tiered infusions totaling 100 mg) are completely different and must never be interchanged. 2, 4 Use full generic or brand names in orders rather than abbreviations like "TPA" or "tPA" to prevent accidental substitution with tenecteplase or reteplase. 5

Weight-Based Dosing Considerations

• The 90 mg maximum dose for stroke is appropriate even for patients >100 kg, as higher per-kilogram dosing in heavier patients is associated with increased symptomatic intracerebral hemorrhage risk. 6