Alteplase, sold under the brand name Activase among others, is a biosynthetic form of human tissue-type plasminogen activator (t-PA). It is a thrombolytic medication used to treat acute ischemic stroke, acute ST-elevation myocardial infarction (a type of heart attack), pulmonary embolism associated with low blood pressure, and blocked central venous catheter. Alteplase is given by injection into a vein or artery. Alteplase is the same as the normal human plasminogen activator produced in vascular endothelial cells and is synthesized via recombinant DNA technology in Chinese hamster ovary cells (CHO). Alteplase causes the breakdown of a clot by inducing fibrinolysis.

It is on the World Health Organization's List of Essential Medicines.

Alteplase is indicated for the treatment of acute ischemic stroke, acute myocardial infarction, acute massive pulmonary embolism, and blocked catheters. Similar to other thrombolytic drugs, alteplase is used to dissolve clots to restore tissue perfusion, but this can vary depending on the pathology. Generally, alteplase is delivered intravenously into the body. To treat blocked catheters, alteplase is administered directly into the catheter.

In adults diagnosed with acute ischemic stroke, thrombolytic treatment with alteplase is the standard of care. Administration of alteplase is associated with improved functional outcomes and reduced incidence of disability. Alteplase used in conjunction with mechanical thrombectomy is associated with better outcomes.

As of 2019, alteplase is the most commonly used medication to treat pulmonary embolism. Alteplase has a short infusion time of 2 hours and a half-life of 4–6 minutes. Alteplase has been approved by the US Food and Drug Administration, and treatment can be done via systemic thrombolysis or catheter-directed thrombolysis.

Systemic thrombolysis can quickly restore right ventricular function, heart rate, and blood pressure in patients with acute PE. However, standard doses of alteplase used in systemic thrombolysis may lead to massive bleeding, such as intracranial hemorrhage, particularly in older patients. A systematic review has shown that low-dose alteplase is safer than and as effective as the standard amount.

Alteplase can be used in small doses to clear blood clots that obstruct a catheter, reopening the catheter so it can continue to be used. Catheter obstruction is commonly observed with a central venous catheter. Currently, the standard treatment for catheter obstructions in the United States is alteplase administration. Alteplase is effective and low risk for treating blocked catheters in adults and children. Overall, adverse effects of alteplase for clearing blood clots are rare. Novel alternatives to treat catheter occlusion, such as tenecteplase, reteplase, and recombinant urokinase, offer the advantage of shorter dwell times than alteplase.

A person should not receive alteplase treatment if testing shows they are not suffering from an acute ischemic stroke or if the risks of treatment outweigh the likely benefits. Alteplase is contraindicated in those with bleeding disorders that increase a person's tendency to bleed and in those with an abnormally low platelet count. Active internal bleeding and high blood pressure are additional contraindications for alteplase. The safety of alteplase in the pediatric population has not been determined definitively. Additional contraindications for alteplase when used specifically for acute ischemic stroke include current intracranial hemorrhage and subarachnoid hemorrhage. Contraindications for use of alteplase in people with a STEMI are similar to those of acute ischemic stroke. People with an acute ischemic stroke may also receive other therapies including mechanical thrombectomy.