Generic
Alteplase
1 brands available in the market
At a glance
Alteplase is a thrombolytic medication that dissolves harmful blood clots in blood vessels. It is used for the treatment of stroke, heart attack and pulmonary embolism.
Description
Alteplase is a recombinant human tissue-type plasminogen activator (t-PA) that produces local fibrinolysis. It promotes thrombolysis by converting plasminogen to plasmin; plasmin degrades fibrin and fibrinogen. It binds to fibrin in a thrombus and initiates local fibrinolysis with limited systemic proteolysis. Treatment should be given as soon as possible but within 3-4.5 hours of stroke symptom onset and within 12 hours of heart attack onset. It is administered intravenously by a doctor. The most common and serious side effect is bleeding (hemorrhage), which can lead to cerebral hemorrhage.
Indications
Acute ischemic stroke (within 3-4.5 hours of symptom onset), acute myocardial infarction (heart attack), pulmonary embolism, central venous catheter occlusion.
Therapeutic class
Fibrinolytic (Thrombolytic)
Pharmacological class
Tissue Plasminogen Activator (t-PA)
Pharmacology
Alteplase is a serine protease responsible for fibrin-enhanced conversion of plasminogen to plasmin. It produces limited conversion of plasminogen in the absence of fibrin. When introduced into the systemic circulation at pharmacologic concentration, alteplase binds to fibrin in a thrombus and converts the entrapped plasminogen to plasmin. This initiates local fibrinolysis with limited systemic proteolysis.
Mechanism of action
Alteplase binds to fibrin in the thrombus and converts plasminogen to plasmin. Plasmin degrades fibrin, dissolving the blood clot and restoring blood flow, which prevents tissue damage and improves patient outcomes.
Dosage
Acute Ischemic Stroke:
- 0.9 mg/kg IV (max 90 mg total dose)
- 10% of total dose as IV bolus over 1 minute, remainder infused over 60 minutes
- Initiate within 3-4.5 hours of symptom onset
- Discontinue if INR >1.7 or aPTT is elevated
Acute Myocardial Infarction (Heart Attack):
- Weight-based dose (max 100 mg)
- Accelerated regimen (1.5 hr): 15 mg IV bolus (1-2 min), then 50 mg over 30 min, remaining 35 mg over 60 min
- 3-hour regimen: 6-10 mg IV bolus, then 50-54 mg in 1st hour, then 20 mg/hour for next 2 hours
Pulmonary Embolism:
- 100 mg IV infusion over 2 hours
Central Venous Catheter Occlusion:
- 2 mg (2 mL) instilled into occluded catheter
- Attempt to aspirate after 30 minutes; 2nd dose may be given after 120 minutes
Administration
For intravenous administration only. Given by a doctor or nurse in a hospital setting.
Reconstitution: Reconstitute with sterile water for injection provided. Use within 8 hours of reconstitution.
Remove excess drug if needed. Extravasation may cause ecchymosis or inflammation; terminate infusion and apply local therapy.
Missed dose
Missed dose is not applicable as it is administered by a doctor in a hospital setting.
Side effects
Most common and serious side effect: Bleeding (hemorrhage) - internal bleeding, cerebral hemorrhage, injection site bleeding, nosebleeds, gum bleeding, black or tarry stools.
Other side effects: Decreased blood pressure, nausea, vomiting, fever, allergic reactions, orolingual angioedema (swelling of tongue and throat), cholesterol embolization, reembolization.
Precautions & warnings
- Bleeding risk: Most serious side effect. Avoid intramuscular injections. Monitor for bleeding. Discontinue alteplase if serious bleeding occurs.
- Angioedema: Monitor during and for several hours after infusion. Discontinue if angioedema develops.
- Cholesterol embolization: Rarely reported with thrombolytic agents.
- Reembolization: Consider risk of reembolization from lysis of underlying DVT in PE patients.
- Pregnancy: Animal studies have shown harmful effects on the fetus; use only if clearly needed.
Contraindications
Acute Ischemic Stroke:
- Current intracranial hemorrhage
- Subarachnoid hemorrhage
- Active internal bleeding
- Recent (within 3 months) intracranial or intraspinal surgery or serious head trauma
- Intracranial conditions that may increase bleeding risk (neoplasms, AVMs, aneurysms)
- Bleeding diathesis
- Current severe uncontrolled hypertension
AMI or PE:
- Active internal bleeding
- History of recent stroke
- Recent (within 3 months) intracranial or intraspinal surgery or serious head trauma
- Bleeding diathesis
- Current severe uncontrolled hypertension
Drug interactions
- Anticoagulants (warfarin, heparin, LMWH): Increased bleeding risk
- Antiplatelet drugs (aspirin, clopidogrel): Increased bleeding risk
- GPIIb/IIIa antagonists: Increased bleeding risk
- ACE inhibitors: May increase risk of anaphylactoid reactions
Food interactions
Information on alcohol consumption is not available; consult your doctor.
Use in pregnancy
Pregnancy Category: C. Animal studies have shown harmful effects on the fetus (embryocidal in rabbits at 3 mg/kg). Use only if clearly needed with medical advice.
Pregnancy Category: C — always consult a doctor before taking during pregnancy.
Use in lactation
It is not known whether alteplase is excreted in human milk. Use with caution.
Pediatric use
Safety and effectiveness in pediatric patients have not been established.
Geriatric use
Elderly patients (over 77 years) have higher risk of intracranial hemorrhage. Efficacy results suggest favorable outcomes. In AMI, patients over 75 years had higher stroke rates (4.0%).
Renal / hepatic impairment
Limited information is available on use in patients with renal or hepatic impairment; consult your doctor.
Overdose effects
Overdose symptoms: bleeding (hemorrhage). Treatment: discontinue alteplase, control bleeding, blood transfusion if needed.
Storage conditions
Store lyophilized alteplase below 30°C or at 2-8°C. Use within 8 hours of reconstitution.
Chemical structure
Recombinant Tissue Plasminogen Activator (rt-PA)