Acute Ischemic Stroke: Alteplase is indicated for the treatment of acute ischemic stroke. Intracranial hemorrhage must be excluded as the cause of symptoms before starting therapy. Treatment 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 management of acute massive pulmonary embolism, defined as:

• Pulmonary emboli obstructing blood flow to one or more lobes or multiple lung segments.
• Pulmonary embolism associated with unstable hemodynamics, such as inability to maintain blood pressure without supportive interventions.

Alteplase is a serine protease that facilitates the conversion of plasminogen to plasmin in the presence of fibrin. In the absence of fibrin, only minimal activation of plasminogen occurs. At therapeutic concentrations in systemic circulation, alteplase selectively binds to fibrin within a thrombus and converts the entrapped plasminogen into plasmin, initiating localized fibrinolysis with minimal systemic proteolytic activity.

Pharmacodynamics: After administration of 100 mg alteplase, circulating fibrinogen levels decrease by approximately 16%–36%. In a controlled study, 8 out of 73 patients (11%) treated with alteplase (1.25 mg/kg over 3 hours) showed a reduction in fibrinogen levels to 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. The initial plasma half-life is similar for both 3-hour and accelerated dosing regimens. Plasma clearance ranges from 380–570 mL/min and is mainly dependent on hepatic metabolism. The initial volume of distribution is approximately equal to plasma volume.

Acute Ischemic Stroke: Administer Alteplase as soon as possible but within 3 hours after onset of symptoms. The recommended dose is 0.9 mg/kg (not to exceed 90 mg total dose), with 10% of the total dose administered as an initial intravenous bolus over 1 minute and the remainder infused over 60 minutes. During and following Alteplase administration for the treatment of acute ischemic stroke, frequently monitor and control blood pressure. In patients without recent use of oral anticoagulants or heparin, Alteplase treatment can be initiated prior to the availability of coagulation study results. Discontinue Alteplase if the pretreatment International Normalized Ratio (INR) is greater than 1.7 or the activated partial thromboplastin time (aPTT) is elevated.

Acute Myocardial Infarction: Administer Alteplase as soon as possible after the onset of symptoms. The recommended total doses for acute myocardial infarction (AMI) is based on patient weight, not to exceed 100 mg, regardless of the selected administration regimen (accelerated or 3 hour). There are two Alteplase dose regimens (accelerated and 3-hour) for use in the management of AMI; there are no controlled studies to compare clinical outcomes with these regimens

Pulmonary Embolism (PE): The recommended dose is 100 mg administered by IV infusion over 2 hours. Institute parenteral anticoagulation near the end of or immediately following the Alteplase infusion when the partial thromboplastin time or thrombin time returns to twice normal or less.

The interaction of alteplase with other cardioactive or cerebroactive medications has not been fully evaluated. The use of anticoagulants or antiplatelet agents before, during, or after alteplase therapy may increase the risk of bleeding. Post-marketing reports have also described cases of orolingual angioedema, particularly in patients with acute ischemic stroke receiving concomitant angiotensin-converting enzyme (ACE) inhibitors.

For Acute Ischemic Stroke (AIS): Do not use Alteplase in the following situations, where the risk of bleeding outweighs any potential benefit:

• Current intracranial hemorrhage (bleeding inside the skull)
• Subarachnoid hemorrhage
• Active internal bleeding
• Recent (within 3 months) intracranial or intraspinal surgery or serious head trauma
• Presence of intracranial conditions that increase bleeding risk (e.g., certain tumors, arteriovenous malformations, or aneurysms)
• Bleeding diathesis (a tendency to bleed)
• Current severe uncontrolled hypertension

For Acute Myocardial Infarction (AMI) or Pulmonary Embolism (PE): Do not use Alteplase in the following situations, where the risk of bleeding outweighs any potential benefit:

• Active internal bleeding
• History of recent stroke
• Recent (within 3 months) intracranial or intraspinal surgery or serious head trauma
• Presence of intracranial conditions that increase bleeding risk (e.g., certain tumors, arteriovenous malformations, or aneurysms)
• Bleeding diathesis
• Current severe uncontrolled hypertension

The following adverse reactions have been reported with the use of Alteplase:

• Bleeding (hemorrhage) – the most common and significant side effect
• Orolingual Angioedema – swelling of the mouth, tongue, and lips
• Cholesterol Embolization – release of cholesterol particles that can block small blood vessels
• Re-embolization of Deep Venous Thrombi – recurrence or movement of blood clots during treatment for acute massive pulmonary embolism

Pregnancy Category C. Alteplase has been shown to be embryocidal in animal studies (rabbits) when administered intravenously at doses approximately twice (3 mg/kg) the human dose used for AMI. No evidence of maternal or fetal toxicity was observed at lower doses (0.65 times; 1 mg/kg) in pregnant rats and rabbits during organogenesis. There are no adequate and well-controlled studies in pregnant women. It is not known whether alteplase is excreted in human breast milk, although many drugs are known to be excreted in milk.

• Bleeding Risk: Alteplase increases the risk of bleeding. Monitor patients closely for any signs of bleeding. If serious bleeding occurs, discontinue Alteplase immediately. Avoid intramuscular injections during treatment.
• Orolingual Angioedema: Monitor patients during and for several hours after the infusion for signs of orolingual angioedema (swelling of the mouth, tongue, or lips). If angioedema develops, discontinue Alteplase.
• Cholesterol Embolism: Rare cases of cholesterol embolism have been reported in patients receiving thrombolytic agents. This can lead to complications in the kidneys, feet, and other organs.
• Re-embolization Risk: In patients being treated for pulmonary embolism, consider the risk of re-embolization due to the lysis (dissolving) of underlying deep venous thrombi.

Pediatric Use: The safety and effectiveness of alteplase in pediatric patients have not been established.

Geriatric Use:

• Acute Ischemic Stroke: Exploratory multivariate analyses from Studies 1 and 2 indicate that age above 77 years is associated with a higher risk of intracranial hemorrhage. However, efficacy data suggest that although outcomes may be reduced, they remain generally favorable in elderly patients treated with alteplase.
• Acute Myocardial Infarction: In a large clinical trial involving 41,021 patients receiving accelerated-infusion alteplase or other thrombolytic regimens, patients older than 75 years accounted for 12% of the study population. Among these patients, the incidence of stroke was 4.0% in the alteplase group, compared with 2.8% for intravenous streptokinase and 3.2% for subcutaneous streptokinase. The combined rate of 30-day mortality or nonfatal stroke was 20.6% with alteplase, 21.5% with IV streptokinase, and 22.0% with subcutaneous streptokinase.

Antiplatelet agents and fibrinolytics (thrombolytic agents).

Store lyophilized alteplase at controlled room temperature not exceeding 30°C or under refrigeration (2–8°C). Protect the lyophilized product from prolonged exposure to light during storage. If stored between 2–30°C, the reconstituted solution should be used within 8 hours. Discard any unused portion after administration. Do not use beyond the expiry date indicated on the vial.