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# Alteplase (tPA) ## Overview Alteplase is a thrombolytic agent that activates plasminogen to form plasmin, which degrades fibrin clots. It is a recombinant tissue plasminogen activator (tPA). ## Primary Indications * **Acute Ischemic Stroke:** To improve neurological outcome by dissolving the blood clot causing the stroke. * **Acute Myocardial Infarction (STEMI):** For lysis of thrombus in patients with ST-elevation myocardial infarction, typically in settings where percutaneous coronary intervention (PCI) is not available within a recommended timeframe. * **Acute Massive Pulmonary Embolism (PE):** To lyse acute pulmonary emboli in hemodynamically unstable patients. ## Adult Dosing * **Acute Ischemic Stroke:** * **Standard Dose:** 0.9 mg/kg IV infusion over 60 minutes. * **Bolus:** Give 0.09 mg/kg (10% of the total dose) as a rapid IV bolus over 1 minute. * **Infusion:** Infuse the remaining 0.81 mg/kg (90% of the total dose) IV over 60 minutes. * **Maximum Dose:** 90 mg. * **Acute Myocardial Infarction (STEMI):** * **Dose:** 100 mg IV infusion over 3 hours. * **Alternative:** 60 mg IV infusion over 3 hours for patients weighing less than 65 kg. * **Bolus:** The first 10 mg should be given as a rapid IV bolus over 1 minute. * **Infusion:** The remaining 90 mg (or 50 mg for lighter patients) is infused over the next 2-3 hours. * **Maximum Dose:** 100 mg. * **Acute Massive Pulmonary Embolism (PE):** * **Dose:** 100 mg IV infusion over 2 hours. * **Maximum Dose:** 100 mg. ## Pediatric Dosing Dosing for pediatric patients is not well established and should be determined by experienced pediatric centers, often based on adult protocols with adjustments for weight and specific condition. ## Dose Adjustments * **Renal Impairment:** No specific dose adjustment is typically recommended due to the acute nature of administration and lack of significant renal excretion. Risk assessment for bleeding is paramount. * **Hepatic Impairment:** No specific dose adjustment is typically recommended. Risk assessment for bleeding is paramount. * **Body Weight:** Dosing is weight-based for ischemic stroke. Maximum doses are capped. ## Contraindications * Active internal bleeding. * History of intracranial hemorrhage. * Recent stroke (ischemic stroke within 3 months, intracranial surgery or severe head trauma within 3 months). * Arteriovenous malformation or neoplasm. * Significant bleeding diathesis (e.g., platelet count < 100,000/mm³, prolonged PTT > 40 sec, INR > 1.7, or current use of therapeutic warfarin). * Severe uncontrolled hypertension (systolic BP > 185 mmHg or diastolic BP > 110 mmHg) or a history of hypertension that makes it difficult to control blood pressure. * Recent major surgery or trauma. * Hypersensitivity to alteplase or any component of the formulation. ## Adverse Effects * **Hemorrhage:** The most significant risk, including intracranial hemorrhage (ICH), gastrointestinal bleeding, genitourinary bleeding, and bleeding at puncture sites. * Hypersensitivity reactions (anaphylaxis, urticaria, angioedema). * Hypotension. * Nausea and vomiting. * Fever. ## Key Drug Interactions * **Anticoagulants (e.g., Heparin, Warfarin, Direct Oral Anticoagulants):** Increased risk of bleeding. Concurrent use is generally avoided or requires extreme caution and careful monitoring. * **Antiplatelet Agents (e.g., Aspirin, Clopidogrel):** Increased risk of bleeding. Concurrent use is often necessary in stroke and MI, but monitoring is crucial. * **Other Thrombolytics:** Concurrent administration is contraindicated. * **ACE Inhibitors:** Cases of angioedema have been reported when used concurrently with ACE inhibitors. ## Monitoring * **Neurological Status:** Frequent assessment (e.g., every 15 minutes during infusion, every 30 minutes for 6 hours post-infusion, then hourly) for stroke patients. * **Vital Signs:** Blood pressure, heart rate, respiratory rate. * **Bleeding:** Monitor for any signs of bleeding (hematuria, epistaxis, melena, bruising, bleeding from IV sites). * **Laboratory Tests:** * **Platelet Count:** Baseline and as needed. * **PT/INR, PTT:** Baseline and as needed to assess coagulation status and rule out other causes of bleeding. * **Hemoglobin/Hematocrit:** Baseline and as needed. * **Cardiac Monitoring:** For MI patients. * **Imaging:** CT or MRI of the brain may be indicated for evaluation of stroke or intracranial hemorrhage. ## Clinical Pearls * **Time is Brain:** Prompt administration in acute ischemic stroke is critical. Initiate treatment as soon as possible after symptom onset and after ruling out contraindications. * **Blood Pressure Management:** Strict blood pressure control is essential before and during alteplase infusion in stroke patients to minimize the risk of hemorrhagic transformation. Target SBP < 185 mmHg and DBP < 110 mmHg for treatment initiation and maintenance of SBP < 180 mmHg during and for 24 hours after treatment. * **Bleeding Precautions:** Minimize invasive procedures (e.g., arterial punctures, bladder catheterization) during and immediately after alteplase therapy. Use radial artery approach for cardiac catheterization if necessary. * **Recombinant Source:** Alteplase is a recombinant product and is not derived from human plasma. * **Reconstitution and Administration:** Follow manufacturer's instructions for reconstitution and administration carefully. Do not administer other medications in the same IV line as alteplase. *** **Disclaimer:** This information is intended for clinical use and is a summary. Always consult the most current prescribing information, institutional protocols, and patient-specific factors before making any treatment decisions.