Activase is indicated for use in acute myocardial infarction (AMI) for the reduction of mortality and reduction of the incidence of heart failure.

Limitation of Use: The risk of stroke may outweigh the benefit produced by thrombolytic therapy in patients whose AMI puts them at low risk for death or heart failure.

Activase is indicated for the lysis of acute massive pulmonary embolism (PE), defined as:

• Acute pulmonary emboli obstructing blood flow to a lobe or multiple lung segments.
• Acute pulmonary emboli accompanied by unstable hemodynamics, e.g., failure to maintain blood pressure without supportive measures.
  

Contraindications
Do not administer Activase to treat acute ischemic stroke in the following situations in which the risk of bleeding is greater than the potential benefit: current intracranial hemorrhage (ICH); subarachnoid hemorrhage; active internal bleeding; recent (within 3 months) intracranial or intraspinal surgery or serious head trauma; presence of intracranial conditions that may increase the risk of bleeding; bleeding diathesis; and current severe uncontrolled hypertension.

Do not administer Activase to treat acute myocardial infarction or pulmonary embolism in the following situations in which the risk of bleeding is greater than the 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 may increase the risk of bleeding; bleeding diathesis; and current severe uncontrolled hypertension.

Warnings and Precautions

Bleeding
Activase can cause significant, sometimes fatal, internal or external bleeding, especially at arterial and venous puncture sites. Avoid intramuscular injections and trauma to the patient. Fatal cases of hemorrhage associated with traumatic intubation in patients administered Activase have been reported. The concomitant administration of heparin and aspirin with and following infusions of Activase during the first 24 hours after symptom onset has not been investigated. Because heparin, aspirin, or Activase may cause bleeding complications, carefully monitor for bleeding, especially at arterial puncture sites. Hemorrhage can occur 1 or more days after administration of Activase, while patients are still receiving anticoagulant therapy. If serious bleeding occurs, terminate the Activase infusion.

In the following conditions, the risks of bleeding with Activase are increased and should be weighed against the anticipated benefits: recent major surgery or procedure; cerebrovascular disease; recent intracranial hemorrhage; recent gastrointestinal or genitourinary bleeding; recent trauma; hypertension; high likelihood of left heart thrombus; acute pericarditis; subacute bacterial endocarditis; hemostatic defects including those secondary to severe hepatic or renal disease; significant hepatic dysfunction; pregnancy; diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions; septic thrombophlebitis or occluded AV cannula at seriously infected site; advanced age; and patients currently receiving oral anticoagulants, or any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location.

Orolingual Angioedema
Orolingual angioedema has been observed during and up to 2 hours after infusion. In many cases, patients received concomitant angiotensin‑converting enzyme inhibitors. Monitor patients treated with Activase during and for several hours after Activase infusion for orolingual angioedema. If angioedema develops, discontinue the Activase infusion and promptly institute appropriate therapy.

Cholesterol Embolization
Cholesterol embolism, sometimes fatal, has been reported rarely in patients treated with thrombolytic agents; the true incidence is unknown. It is associated with invasive vascular procedures and/or anticoagulant therapy.

Reembolization of Deep Venous Thrombi during Treatment for Acute Massive Pulmonary Embolism
Activase has not been shown to treat adequately underlying deep vein thrombosis in patients with PE. Consider the possible risk of reembolization due to the lysis of underlying deep venous thrombi in this setting.

Coagulation Tests May be Unreliable during Activase Therapy
Coagulation tests and/or measures of fibrinolytic activity may be unreliable during Activase therapy unless specific precautions are taken to prevent in vitro artifacts.

Adverse Reactions
The most frequent adverse reaction associated with Activase therapy is bleeding.

Although exploratory analyses of the AIS clinical studies suggest that severe neurological deficit (National Institutes of Health Stroke Scale [NIHSS > 22]) at presentation was associated with an increased risk of intracranial hemorrhage, efficacy results suggest a reduced but still favorable clinical outcome for these patients.

Allergic‑type reactions, e.g., anaphylactoid reaction, laryngeal edema, orolingual angioedema, rash, and urticaria have been reported.

Please see full Prescribing Information for additional Important Safety Information.