ACTIVASE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ACTIVASE (ACTIVASE).
Tissue plasminogen activator that converts plasminogen to plasmin, degrading fibrin clots.
| Metabolism | Primarily hepatic metabolism via unknown enzymes; rapid clearance. |
| Excretion | Primarily hepatic clearance; renal excretion negligible, <1% unchanged in urine. Fecal elimination unknown as endogenous enzyme. |
| Half-life | 4-6 minutes initially (alpha phase), then terminal half-life of 20-40 minutes for fibrin-bound alteplase; clinical context: requires continuous infusion. |
| Protein binding | ~80% bound to fibrin and fibronectin; minimal binding to albumin. |
| Volume of Distribution | Approximately 0.5-0.7 L/kg; distributes into extracellular fluid. |
| Bioavailability | Only IV/IC route; not administered orally; 100% bioavailability IV. |
| Onset of Action | IV: immediate thrombolytic effect within 1-2 minutes; intracoronary: recanalization within 15-30 minutes. |
| Duration of Action | Thrombolytic effect persists for 1-2 hours after IV infusion cessation; fibrinogen depletion lasts up to 24 hours. |
Acute ischemic stroke: 0.9 mg/kg IV (max 90 mg) infused over 60 minutes, with 10% of total dose given as IV bolus over 1 minute. Acute myocardial infarction: Total dose of 100 mg administered IV as a 15 mg bolus, then 50 mg infused over 30 minutes, then 35 mg infused over 60 minutes. Pulmonary embolism: 100 mg IV infused over 2 hours.
| Dosage form | VIAL |
| Renal impairment | No dose adjustment required based on GFR. Use caution in patients with severe renal impairment (CrCl <30 mL/min) due to increased bleeding risk, but no specific dose modification. |
| Liver impairment | No formal dose adjustment guidelines for hepatic impairment. Use caution in patients with significant hepatic disease (Child-Pugh Class B or C) due to potential coagulopathy; contraindicated in patients with active bleeding or bleeding diathesis. |
| Pediatric use | Not FDA-approved for pediatric use. Limited data: For acute ischemic stroke in children, a suggested dose is 0.9 mg/kg IV (max 90 mg) based on adult protocols, but use is not standard. For other indications, consult expert guidelines. |
| Geriatric use | Consider increased risk of bleeding, especially in patients >75 years. Dose same as adults for acute ischemic stroke (0.9 mg/kg, max 90 mg). No dose adjustment required based on age alone, but careful patient selection and monitoring are essential. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ACTIVASE (ACTIVASE).
| Breastfeeding | No data on excretion into human milk. M/P ratio unknown. Alteplase is a large protein; likely minimal transfer. Use with caution in nursing mothers only if clearly needed. |
| Teratogenic Risk | Pregnancy Category C. Alteplase crosses the placenta; risk of hemorrhage in fetus. First trimester: theoretical risk of placental abruption; avoid unless life-threatening. Second/third trimesters: increased risk of premature labor, placental abruption, fetal hemorrhage. Use only if maternal benefit outweighs fetal risk. |
■ FDA Black Box Warning
Increases risk of intracranial hemorrhage; not indicated for minor or rapidly improving stroke symptoms.
| Serious Effects |
Active internal bleeding, recent intracranial or intraspinal surgery or trauma, intracranial neoplasm, arteriovenous malformation or aneurysm, known bleeding diathesis, severe uncontrolled hypertension.
| Precautions | Risk of bleeding (intracranial, gastrointestinal, genitourinary); monitor for signs of hemorrhage; avoid in patients with active internal bleeding or recent major surgery. |
| Food/Dietary | No known food interactions. Maintain adequate hydration. Avoid alcohol consumption during treatment due to increased bleeding risk. |
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| Fetal Monitoring |
| Monitor for signs of bleeding (gums, nose, injection sites, urine, stool, vaginal bleeding). Assess uterine activity and fetal heart rate during and after infusion. Coagulation parameters (PT, aPTT, fibrinogen) not routinely required but may be checked if bleeding suspected. |
| Fertility Effects | No human data on fertility effects. Animal studies not conducted. Alteplase is not expected to impair fertility based on its mechanism (fibrinolytic) and short half-life. |
| Clinical Pearls |
| Administer within 3 hours (up to 4.5 hours in selected patients) of ischemic stroke onset. Use alteplase with caution in patients with recent major surgery, active internal bleeding, or severe uncontrolled hypertension. Do not mix with other medications; administer via dedicated IV line. Monitor for signs of intracranial hemorrhage; discontinue if bleeding occurs. Weight-based dosing: 0.9 mg/kg (max 90 mg) for stroke; 100 mg for acute myocardial infarction. |
| Patient Advice | This medication is a clot buster and increases bleeding risk. Report any sudden headache, nausea, vomiting, or neurological changes immediately. · You may experience bruising or bleeding at injection sites. Avoid shaving or brushing teeth vigorously during treatment. · Inform all healthcare providers you are taking this drug. Do not take aspirin or other blood thinners unless prescribed. · For stroke treatment, you must receive this drug within a few hours of symptom onset. Call 911 immediately if you suspect a stroke. |