Acute Ischemic Stroke: Alteplase is indicated for the management of acute ischemic stroke. Intracranial hemorrhage must be ruled out as the main cause of symptoms before starting treatment. Therapy should be initiated as early as possible, preferably within 3 hours of symptom onset.

Acute Myocardial Infarction: Alteplase is indicated for use in acute myocardial infarction (AMI) to reduce mortality and decrease the risk of heart failure.

Pulmonary Embolism: Alteplase is indicated for the treatment of acute massive pulmonary embolism, defined as:

• Acute emboli blocking blood flow to one or more lobes of the lungs.
• Pulmonary embolism associated with unstable hemodynamics, such as inability to maintain blood pressure without supportive therapy.

Alteplase is a serine protease that promotes the conversion of plasminogen to plasmin in the presence of fibrin. In the absence of fibrin, only minimal conversion occurs. At therapeutic levels in the bloodstream, it binds to fibrin within a clot and activates plasminogen trapped in the thrombus, leading to localized clot breakdown (fibrinolysis) with minimal systemic effects.

Pharmacodynamics: After administration of 100 mg Alteplase, circulating fibrinogen levels decrease by approximately 16%–36%. In controlled studies, about 11% of patients (8 out of 73) receiving Alteplase (1.25 mg/kg over 3 hours) showed fibrinogen levels dropping below 100 mg/dL.

Pharmacokinetics: In patients with acute myocardial infarction (AMI), Alteplase is rapidly cleared from plasma, with an initial half-life of less than 5 minutes. There is no significant difference in this initial half-life between 3-hour and accelerated dosing regimens. Plasma clearance ranges from 380–570 mL/min and is mainly mediated by the liver. The initial distribution volume is similar to plasma volume.

Acute Ischemic Stroke: Administer Alteplase as early as possible, preferably within 3 hours of symptom onset. The recommended dose is 0.9 mg/kg (maximum 90 mg), with 10% given as an initial IV bolus over 1 minute and the remaining dose infused over 60 minutes. Blood pressure should be closely monitored during and after administration. In patients without recent use of oral anticoagulants or heparin, treatment may begin before coagulation test results are available. Discontinue Alteplase if the pretreatment INR is greater than 1.7 or if aPTT is elevated.

Acute Myocardial Infarction: Administer Alteplase as soon as possible after symptom onset. The total dose for AMI is weight-based and should not exceed 100 mg, regardless of whether an accelerated or 3-hour regimen is used. Both dosing regimens are used in clinical practice, though comparative outcome data are limited.

Pulmonary Embolism (PE): The recommended dose is 100 mg administered by IV infusion over 2 hours. Parenteral anticoagulation should be started near the end of or immediately after Alteplase infusion when clotting parameters return to acceptable levels.

Following bolus dose, if indicated:

• 50 mg vials: administer using a polyvinyl chloride bag or glass vial with an infusion set.
• 100 mg vials: remove any excess drug not required for dosing. Insert the infusion set spike through the same puncture site used for transfer. Remove the plastic hanger from the vial label and hang the vial appropriately.

Alteplase is intended for intravenous use only. Extravasation may cause bruising or inflammation; if it occurs, stop the infusion and manage locally. Do not mix Alteplase with other drugs in the same infusion solution.

The interaction of Alteplase with other cardioactive or cerebroactive medications has not been well established. Use of anticoagulants and antiplatelet agents before, during, or after Alteplase therapy may increase the risk of bleeding. Post-marketing reports have also noted cases of orolingual angioedema, especially in patients (mainly those with AIS) receiving concomitant angiotensin-converting enzyme (ACE) inhibitors.

Acute Ischemic Stroke: Alteplase should not be used in acute ischemic stroke when the risk of bleeding outweighs the potential benefit, including the following conditions:

• Ongoing intracranial hemorrhage
• Subarachnoid hemorrhage
• Active internal bleeding
• Recent (within 3 months) intracranial or intraspinal surgery or significant head injury
• Presence of intracranial disorders that increase bleeding risk (e.g., certain tumors, arteriovenous malformations, or aneurysms)
• Bleeding disorders (diathesis)
• Severe uncontrolled hypertension

Acute Myocardial Infarction or Pulmonary Embolism: Alteplase should not be used for AMI or PE when bleeding risk exceeds the expected benefit, including:

• Active internal bleeding
• Previous stroke history
• Recent (within 3 months) intracranial or intraspinal surgery or serious head trauma
• Intracranial conditions associated with increased bleeding risk (e.g., tumors, AV malformations, aneurysms)
• Bleeding disorders
• Severe uncontrolled hypertension

The following adverse reactions may occur:

• Bleeding
• Orolingual angioedema
• Cholesterol embolization
• Re-embolization of deep venous thrombi during treatment of acute massive pulmonary embolism

Pregnancy Category C. In animal studies, Alteplase showed embryocidal effects in rabbits when given intravenously at doses about twice (3 mg/kg) the human dose for AMI. No maternal or fetal toxicity was observed at approximately 0.65 times (1 mg/kg) the human dose in rats and rabbits during organ formation. Adequate and well-controlled studies in pregnant women are lacking. It is not known whether Alteplase is excreted in human breast milk, although many drugs are known to be present in breast milk.

• May increase the risk of bleeding. Avoid intramuscular injections and monitor for signs of bleeding. If significant bleeding occurs, discontinue Alteplase.
• Observe patients during and for several hours after infusion for signs of orolingual angioedema. If it develops, stop Alteplase.
• Cholesterol embolism has been rarely reported in patients receiving thrombolytic therapy.
• Consider the possibility of re-embolization due to breakdown of underlying deep venous thrombi in patients with pulmonary embolism.

Pediatric Use: The safety and efficacy of Alteplase in pediatric patients have not been established.

Geriatric Use:

• Acute Ischemic Stroke: Exploratory analyses of clinical studies indicate that patients older than 77 years have a higher risk of intracranial hemorrhage. However, outcomes suggest a reduced yet still beneficial clinical effect in elderly patients treated with Alteplase.
• Acute Myocardial Infarction: In a large clinical trial involving patients with AMI, those aged over 75 years showed varying stroke incidence across treatment regimens. The combined rate of mortality or nonfatal stroke was comparable among different thrombolytic therapies.

Anti-platelet drugs, Fibrinolytics (Thrombolytics)

Store lyophilized Alteplase at controlled room temperature not exceeding 30°C or under refrigeration (2–8°C). Protect from excessive light exposure during storage. If stored at 2–30°C after reconstitution, use within 8 hours. Discard any unused solution after administration. Do not use beyond the expiry date mentioned on the vial.