Alteplase

• Acute Ischemic Stroke: Treatment to restore blood flow by thrombolysis within a specified time window (generally within 4.5 hours of symptom onset).
• Acute Myocardial Infarction (STEMI): For reperfusion therapy to dissolve thrombi occluding coronary arteries.
• Pulmonary Embolism (PE): Treatment of massive PE with hemodynamic instability.
• Acute Occlusion of Central Venous Access Devices: To restore patency of catheters and cannulas.
• Off-label Uses: Occasionally used for peripheral arterial or venous thrombosis, but less common.

• Acute Ischemic Stroke:
• Dose: 0.9 mg/kg (maximum 90 mg), with 10% of total dose given as an initial IV bolus over 1 minute, and remainder infused over 60 minutes.
• Acute Myocardial Infarction:
• Dose varies by protocol, often 100 mg over 1.5 to 2 hours.
• Pulmonary Embolism:
• Dose: 100 mg infused over 2 hours; alternative regimens may be used based on clinical judgment.
• Central Venous Catheter Occlusion:
• Dose: 2 mg instilled into the catheter lumen and allowed to dwell for 30 minutes.
• Special Populations:
• Use with caution in elderly patients and those with hepatic or renal impairment; dose adjustments usually not established but careful monitoring advised.
• Route: Intravenous administration or catheter-directed infusion depending on indication.
• Duration: Single treatment dose per episode; repeated dosing only under specialist guidance.

Alteplase is a recombinant tissue plasminogen activator (rt-PA) that binds to fibrin in a thrombus and converts the entrapped plasminogen to plasmin. Plasmin is a proteolytic enzyme that degrades fibrin clots, leading to clot dissolution (fibrinolysis). By selectively activating plasminogen in the presence of fibrin, alteplase promotes targeted thrombolysis, restoring blood flow in occluded vessels, thereby improving tissue perfusion and reducing ischemic injury.

• Absorption: Administered intravenously; immediate systemic availability.
• Distribution: Rapidly distributed in plasma; volume of distribution approximately 0.05 L/kg.
• Metabolism: Primarily hepatic metabolism by proteolytic cleavage and clearance.
• Half-life: Biphasic elimination with initial half-life ~5 minutes and terminal half-life approximately 40 minutes.
• Elimination: Cleared mainly by the liver via receptor-mediated endocytosis; inactive metabolites excreted in urine.

• Pregnancy: Category C. Limited data in pregnant women; use only if potential benefit justifies potential risk. Risks include bleeding complications.
• Lactation: Unknown if excreted in human milk; caution advised. Risk of bleeding in infant theoretically low but data insufficient.

• Primary Class: Thrombolytic agent (Fibrinolytic)
• Subclass: Recombinant tissue plasminogen activator (rt-PA)

• Active internal bleeding or bleeding diathesis
• Recent intracranial or intraspinal surgery or trauma (within 3 months)
• History of hemorrhagic stroke or intracranial hemorrhage
• Severe uncontrolled hypertension (e.g., systolic >185 mmHg or diastolic >110 mmHg before treatment)
• Known intracranial neoplasm, arteriovenous malformation, or aneurysm
• Suspected aortic dissection
• Recent gastrointestinal or urinary tract bleeding (within 21 days)
• Platelet count <100,000/mm³ or other coagulation disorders

• Risk of serious and sometimes fatal bleeding including intracranial hemorrhage.
• Monitor closely for signs of bleeding during and after administration.
• Avoid invasive procedures during and shortly after therapy unless absolutely necessary.
• Use with caution in elderly patients and those with recent major surgery or trauma.
• Careful blood pressure control essential before and during therapy.
• Hypersensitivity reactions possible; discontinue if signs occur.
• Not recommended outside approved time windows for ischemic stroke to avoid increased hemorrhagic risk.

• Common:
• Bleeding at catheter sites or minor mucosal bleeding
• Hypotension
• Fever
• Serious:
• Intracranial hemorrhage
• Gastrointestinal bleeding
• Allergic reactions including anaphylaxis (rare)
• Reperfusion arrhythmias (e.g., ventricular tachycardia)
• Timing: Most bleeding events occur during or shortly after infusion.

• Increased bleeding risk with anticoagulants (e.g., heparin, warfarin) or antiplatelet agents (e.g., aspirin, clopidogrel).
• Concomitant use with other fibrinolytic or thrombolytic agents contraindicated.
• Use caution with nonsteroidal anti-inflammatory drugs (NSAIDs) due to additive bleeding risk.
• No significant CYP450 enzyme involvement.

• Updated stroke guidelines recommend alteplase administration within 4.5 hours of ischemic stroke onset.
• Emphasis on blood pressure control and exclusion of contraindications prior to administration.
• Recent studies explore extended time windows and combined thrombectomy plus alteplase therapy in select patients.
• Regulatory authorities reinforce strict criteria for patient selection to minimize hemorrhagic complications.

• Store lyophilized powder at 2°C to 8°C (36°F to 46°F).
• Protect from light and moisture; keep in original packaging until use.
• After reconstitution, use immediately or store at room temperature (20°C to 25°C) and use within 8 hours if diluted.
• Do not freeze reconstituted solutions.