Alteplase Dosing
For acute ischemic stroke, administer alteplase at 0.9 mg/kg (maximum 90 mg) over 60 minutes with 10% given as an initial bolus over 1 minute, within 3-4.5 hours of symptom onset. 1
Acute Ischemic Stroke Dosing
The standard dosing regimen is clearly defined by the 2018 AHA/ASA guidelines:
- Total dose: 0.9 mg/kg (maximum 90 mg)
- Administration: 60-minute infusion
- Bolus: 10% of total dose given over 1 minute initially
- Remaining 90%: Infused over the subsequent 59 minutes 1
Time Windows and Eligibility
Within 3 hours of symptom onset:
- Use the standard 0.9 mg/kg dose for all eligible patients ≥18 years
- No age restrictions—equally recommended for patients <80 and >80 years
- Indicated even for severe stroke symptoms despite increased hemorrhagic risk 1
3-4.5 hour window:
- Same dosing (0.9 mg/kg, max 90 mg)
- More restrictive eligibility: patients must be ≤80 years, without both diabetes AND prior stroke, NIHSS ≤25, not on oral anticoagulants, and without imaging showing >1/3 MCA territory involvement 1
Critical Pre-Treatment Requirements
Before administering alteplase, ensure:
- Blood pressure <185/110 mm Hg (can use antihypertensives to achieve this) 1
- Glucose >50 mg/dL 1
- No intracranial hemorrhage on CT 1
- Time last known well is documented and within the appropriate window 1
Post-Treatment Blood Pressure Management
Maintain BP <180/105 mm Hg for at least 24 hours after alteplase administration 1. This is critical for reducing hemorrhagic transformation risk.
Central Venous Catheter Occlusion Dosing
For restoring function to occluded central venous access devices, the FDA-approved dosing differs substantially:
Adults and children ≥30 kg:
- 2 mg in 2 mL instilled into the catheter lumen 2
Children <30 kg:
- 110% of internal lumen volume, not to exceed 2 mg in 2 mL 2
Administration Protocol for Catheter Occlusion
- Instill appropriate dose into occluded catheter
- Assess function at 30 minutes by attempting to aspirate blood
- If unsuccessful, reassess at 120 minutes
- Second dose may be given if first dose fails (same amount as initial dose)
- Maximum total dose: 4 mg (two 2-mg doses) 2
The efficacy for catheter restoration is approximately 85% after up to two doses, with 52% responding within 30 minutes of the first dose 2. In pediatric patients (ages 2-18), efficacy was 87% with similar safety profile 3.
Important Dosing Considerations and Pitfalls
Dose Variations by Geography
While 0.9 mg/kg is the international standard, Japan uses 0.6 mg/kg based on their clinical trials showing comparable efficacy/safety in Asian populations 4. However, this lower dose is not recommended outside of Japan and should not be used in standard practice elsewhere.
Extended Window Treatment
Recent evidence suggests alteplase beyond 4.5 hours may benefit imaging-selected patients, but this remains off-label and should use the same 0.9 mg/kg dosing when employed 5. The ATLANTIS trial demonstrated no benefit and increased hemorrhagic risk when treating 3-5 hours without advanced selection criteria 6.
Common Pitfalls to Avoid
Do not:
- Exceed 90 mg total dose for stroke (even in patients >100 kg)
- Apply vigorous suction or excessive pressure when dealing with catheter occlusions—this can rupture the catheter or dislodge clot 2
- Administer antithrombotic therapy within 24 hours post-alteplase unless compelling indication exists 1
- Use if time last known well exceeds the treatment window, even if current symptoms are within window 1
Critical safety note: Symptomatic intracranial hemorrhage risk increases significantly with alteplase (approximately 7% vs 1% with placebo in extended windows) 6. The orolingual angioedema that can occur is bradykinin-mediated, not histamine-mediated, and should be treated accordingly—not with antihistamines alone 7.
Reconstitution for Catheter Use
When using Cathflo Activase for catheters, reconstitute with 2.2 mL Sterile Water for Injection to achieve 1 mg/mL concentration. Do not use Bacteriostatic Water. Use within 8 hours of reconstitution when stored at 2-30°C 2.