BLACK BOX WARNING
- intracranial hemorrhage risk; careful patient selection essential
alteplase
Brand: Activase, Cathflo Activase
⚠ BBW ISMP High Alert Prototype Drug
Drug Class: thrombolytic agent
Drug Family: thrombolytic
Subclass: recombinant tissue plasminogen activator (tPA)
Organ Systems: cardiovascularhematology-oncology
Mechanism of Action
Recombinant human tPA that preferentially binds fibrin within a thrombus and converts plasminogen to plasmin, causing clot dissolution; fibrin binding concentrates thrombolytic activity at the clot site, minimizing systemic plasminogen activation.
plasminogen (fibrin-bound)fibrin clot
Indications
- acute ischemic stroke (within 3-4.5 hours of symptom onset)
- acute STEMI
- massive pulmonary embolism
- occluded central venous access devices (Cathflo)
Contraindications
- active internal bleeding
- recent (within 3 months) intracranial or intraspinal surgery or trauma
- history of intracranial hemorrhage
- intracranial neoplasm
- AV malformation
- severe uncontrolled hypertension
- suspected aortic dissection
Adverse Effects
Common
- bleeding at puncture sites
- ecchymosis
- epistaxis
Serious
- intracranial hemorrhage
- major systemic bleeding
- angioedema (with ACE inhibitor use)
- embolic events (cholesterol embolism)
Pharmacokinetics (ADME)
| Absorption | IV administration only |
| Distribution | rapidly distributed; Vd approximately 4-8 L (blood volume) |
| Metabolism | rapidly cleared by the liver; endocytosis via LRP1 receptor |
| Excretion | hepatic metabolism; minimal renal excretion |
| Half-life | approximately 5 minutes (initial); approximately 26 minutes (terminal) |
| Onset | immediate (IV) |
| Peak | end of infusion |
| Duration | fibrinolysis continues for up to 1 hour after infusion |
| Protein Binding | low |
| Vd | 4-8 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| anticoagulants (heparin, warfarin, DOACs) | increased bleeding risk when used concurrently or before/after thrombolysis | major |
| antiplatelet agents (aspirin, clopidogrel) | additive risk of intracranial and systemic hemorrhage | major |
| ACE inhibitors | angioedema risk increased with alteplase; mechanism involves bradykinin | moderate |
Nursing Considerations
- Obtain IV access in non-compressible sites before alteplase administration; avoid arterial punctures during and for 24 hours after infusion; apply pressure for at least 30 minutes to any compressible bleeding site.
- Monitor neurological status every 15 minutes during infusion and every 30 minutes for 6 hours post-infusion; any decline in neurological status, new headache, nausea, or vomiting suggests intracranial hemorrhage — STOP infusion and notify physician immediately.
- Hold heparin during alteplase infusion for STEMI; do not administer aspirin or anticoagulants for 24 hours post-infusion in stroke patients without imaging confirmation of no hemorrhage.
- Strict blood pressure management is essential in stroke: maintain BP below 185/110 mmHg before and during alteplase infusion; use IV labetalol or nicardipine per protocol.
Clinical Pearls
- For acute ischemic stroke, the therapeutic window extends to 4.5 hours from symptom onset in eligible patients; time is brain — every 30-minute delay to treatment reduces the number of patients who regain independent function.
- Alteplase doses differ significantly by indication: 0.9 mg/kg (max 90 mg) for stroke, 100 mg over 2 hours for massive PE — nursing staff must confirm the indication and correct dosing regimen before administration.
Safety Profile
Pregnancy use-with-caution
Lactation insufficient-data
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.