Alteplase

TPA, Activase, and Cathflo Activase are brand names available for alteplase.

Alteplase is part of the drug class:

• Antithrombotic Enzymes

Serious side effects have been reported with alteplase including the following:

• Bleeding. Tell your healthcare provider right away if you have some or all of the following symptoms of bleeding.
  • bruising
  • bloody or black, tarry stools
  • bloody vomit
  • vomiting blood or brown material that resembles coffee grounds

Do not take alteplase if you:

• are allergic to alteplase or any of its ingredients
• have an active bleed
• have a history of a brain injury
• have had recent major surgery or trauma especially in the head
• serevely uncontrolled high blood pressure
• have or have had any problems managing bleeding conditions in the past

Before taking alteplase, tell your doctor about all of your medical conditions. Especially tell your doctor is you:

• are allergic to alteplase or any of its ingredients
• are over 75 years old
• are pregnant or breastfeeding
• are taking oral anticoagulants (blood thinners), see the “Alteplase Drug Interactions” section.
• have had recent major surgery or trauma
• have had a previous stroke or heart attack
• have had black, tarry stools or blood in the urine recently
• have hypertension (high blood pressure): systolic BP ≥175 mm Hg and/or diastolic BP ≥110 mm Hg
• have had a recent infection
• have heart problems
• have eye problems 
• have kidney problems
• have liver problems
• have or have had any problems managing bleeding conditions in the past

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Ask your doctor before taking aspirin or ibuprofen (Motrin, Advil) shortly after you have received alteplase. These medications can increase your risk of bleeding.

Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.

Contraindications

Acute MI or PE

• Active internal bleeding.1 2 310 311 352

• History of cerebrovascular accident or intracranial hemorrhage.1 2 310 311 352

• Intracranial neoplasm.1 2 310 311 352

• Aneurysm.1 2 310 311 352

• Recent intracranial or intraspinal surgery or trauma.1 2 310 311 352

• Known bleeding diathesis.1 2 154 310 311 352

• Arteriovenous malformation.1 2 154 310 311 352

• Severe uncontrolled hypertension.1 2 154 310 311 352

• Suspected aortic dissection.1 2 154 310 311 352

Acute Ischemic Stroke

• Evidence of active internal bleeding, intracranial hemorrhage on pretreatment evaluation, suspicion of subarachnoid hemorrhage, history of intracranial hemorrhage, or recent (within 3 weeks) GI or urinary tract hemorrhage.1 322 358 360

• Known bleeding diathesis.1 322 358 360

• Recent (within 3 months) intracranial or intraspinal surgery, serious head trauma, or recent previous stroke.1 322 358 360

• Uncontrolled hypertension at time of treatment (e.g., SBP or DBP >185 or 110 mm Hg, respectively) or hypertension requiring aggressive treatment.1 322 358 360

• Arteriovenous malformation or aneurysm.1 322 358 360

• Seizure at onset of stroke.1 322 358 360

• Intracranial neoplasm.1 322 358 360

Warnings/Precautions

Warnings

Routine monitoring of hemostatic indices (e.g., fibrinogen concentrations, thrombin times) generally not recommended during therapy for acute MI.15 221 222 However, such monitoring is recommended for patients who exhibit bleeding.222

Possible bleeding and hemorrhagic complications,1 14 43 44 62 145 146 154 155 156 including intracranial hemorrhage and other major bleeding complications.141 222 May be more common in geriatric patients62 154 156 and those with a history of cerebrovascular accident or severe or poorly controlled hypertension.141 222

Weigh increased risks of therapy against anticipated benefits in patients with recent major surgery (e.g., coronary artery bypass), cerebrovascular disease, obstetric delivery, organ biopsy, previous puncture of noncompressible vessels, hypertension (SBP ≥175 mm Hg and/or DBP ≥110 mm Hg);1 2 310 311 322 high likelihood of hemostatic defects (e.g., secondary to severe hepatic or renal disease), internal (e.g., GI or GU) bleeding, or recent (within 2–4 weeks) trauma.1 2 222 310 311 Also, weigh risks against benefits of therapy in patients with diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions.1 2 310 311 Weigh risks against benefits in patients receiving concurrent oral anticoagulant therapy (e.g., warfarin).1 2 310 311 Weigh risks against benefits in patients with any condition in which bleeding constitutes a substantial hazard or would be particularly difficult to manage because of its location.1 2 310 311

Initiate therapy only after careful screening for contraindications (e.g., previous neurologic events, severe hypertension, and potential bleeding sites).142 244

Minimize risk of bleeding by carefully selecting patients and monitoring all potential bleeding sites (e.g., sites of all venous cutdowns, arterial and venous punctures, needle punctures).1 14 15 44 46 154 Avoid IM injections and nonessential handling of patient.1 46 Perform invasive venous procedures carefully and as infrequently as possible.1 46 If bleeding from the site of an invasive procedure or other trauma is not serious, continue therapy and closely observe the patient;221 222 initiate local measures (e.g., application of pressure) immediately.1 Avoid arterial and venous invasive procedures in areas inaccessible to manual compression (e.g., internal jugular or subclavian punctures) before and during therapy.1 221 222 Use of an artery in an upper extremity (e.g., radial or brachial) is preferable if arterial puncture is essential.1 46 222 Apply pressure to the puncture site for ≥30 minutes, followed by a pressure dressing and frequent inspection of the puncture site for bleeding.1 155

Possible severe and fatal spontaneous bleeding (e.g., cerebral,1 34 37 42 43 47 48 retroperitoneal,1 37 44 47 GU,1 31 41 44 47 respiratory tract,1 GI bleeding).1 33 36 39 41 43 44 47 48 154 Less severe spontaneous bleeding (e.g., superficial hematoma or ecchymoses,1 40 41 48 hematuria,41 43 hemoptysis,41 43 epistaxis,1 and gingival bleeding)1 41 43 also may occur.40 41

If serious spontaneous bleeding occurs, immediately discontinue alteplase therapy1 14 and initiate appropriate hemostatic therapy as needed.14 15 221 222 If serious bleeding at a critical location (e.g., intracranial, GI, retroperitoneal, pericardial) occurs with intracatheter instillation of alteplase, discontinue therapy immediately and withdraw the drug from the catheter.325

Extravasation during IV infusion may cause ecchymosis and/or inflammation.1 Terminate infusion at that IV site and apply local therapy.1

Possible fatal cardiogenic shock, heart failure, myocardial rupture, electromechanical dissociation, pericardial effusion, pericarditis, mitral regurgitation, cardiac tamponade, hypotension, pulmonary edema, thromboembolism, or recurrent thromboembolic events.1

Weigh risks against anticipated benefits of therapy in patients with a high likelihood of left heart thrombus (e.g., mitral stenosis with atrial fibrillation, profound left ventricular dyskinesia),1 2 196 acute pericarditis,1 2 198 subacute bacterial endocarditis, septic thrombophlebitis, or an occluded arteriovenous cannula at a seriously infected site.1 2 222 310 311

Possible coronary artery reocclusion.4 14 31 34 35 37 39 40 41 60 74 208 Reocclusion rate greater with standard than with accelerated infusion.316 Reduce incidence of reocclusion through concomitant anticoagulation (e.g., heparin and/or oral anticoagulants)1 2 30 31 32 33 34 35 36 37 38 39 40 41 42 47 and/or platelet-aggregation inhibitor (e.g., aspirin, dipyridamole) therapy,1 37 38 39 40 41 43 193 prolonged infusion of the thrombolytic agent, or mechanical or surgical revascularization procedures.4 14 35 37 38 62 63 177

Possible thromboembolism or recurrent thromboembolic events, pleural effusion, hypotension, pulmonary edema, or fever.1 Confirm diagnosis objectively using pulmonary angiography or a noninvasive procedure (e.g., lung scanning).1 277 Potential risk of re-embolization resulting from lysis of deep venous thrombi.1 May not be adequate therapy for underlying DVT.1

Potential new embolic episodes, including those involving cerebral vessels.196 221 222 Avoid therapy in patients with arterial emboli originating from the left side of the heart (e.g., mitral stenosis accompanied by atrial fibrillation, left ventricular thrombi).196 221 222

Possible risk of stroke or intracranial hemorrhage in patients with acute MI who are at low risk for cardiovascular death (e.g., no previous MI, Killip class I) and who have high BP (SBP ≥175 mm Hg and/or DBP ≥110 mm Hg); risk may offset the survival benefit of thrombolytic therapy.1 311

Weigh increased risks of therapy associated with cerebrovascular disease against anticipated benefits of therapy.1 2 222 310 311 322

Manufacturer suggests weighing risks of intracranial hemorrhage against anticipated benefits of therapy in patients with severe neurologic deficit (e.g., NIHSS score >22) on pretreatment evaluation of acute ischemic stroke1 357 and in patients with major early infarct signs on CT scan (e.g., substantial edema, mass effect, midline shift).1 However, AHA and ASA state that thrombolytic therapy almost always should not be administered to patients with major early infarct signs.358

In patients with acute ischemic stroke, administer in facilities that can provide appropriate evaluation and management of intracranial hemorrhage.1 360 Incidence of intracranial hemorrhage and benefits of therapy unknown in patients treated >3 hours after the onset of symptoms; use not recommended in such patients and in patients with symptoms of unknown duration.1 322 358 Frequently monitor and control BP during and following administration.1 357 Safety of administration without careful BP management not established.1 2 322

Possibly fatal cholesterol crystal embolization associated with invasive vascular procedures (e.g., cardiac catheterization, angiography, vascular surgery) and/or anticoagulant therapy.1 Clinical features of cholesterol embolism include livedo reticularis, “purple toe” syndrome, acute renal failure, gangrenous digits,1 267 hypertension, pancreatitis, MI, cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction, and rhabdomyolysis.1 267

Possible reperfusion-related atrial1 32 162 163 164 166 and/or ventricular1 67 162 163 164 165 187 arrhythmias (e.g., accelerated idioventricular rhythm,67 155 162 163 187 VPCs,67 162 atrial fibrillation,163 165 atrial premature complexes,166 junctional rhythm,163 VT,162 sinus bradycardia).32 67 155 162 163 164 Such arrhythmias are usually transient.187

Careful monitoring recommended.1 164 Have appropriate antiarrhythmic therapy available during and immediately after administration.1 164

Weigh anticipated benefits of therapy against increased risks associated with substantial liver dysfunction.1 2 222 310 311

Sensitivity Reactions

Allergic-type reactions (e.g., anaphylactoid reaction, laryngeal edema, orolingual edema, rash, urticaria) occur rarely.1 2 145 Many of the patients experiencing orolingual edema were receiving concomitant ACE inhibitors.1

Monitor patients during and several hours following infusion for signs of orolingual angioedema.1 Administer appropriate therapy (e.g., antihistamines, epinephrine, IV corticosteroids).1 Consider discontinuance of the drug.1

Cautious use recommended in patients who previously received the drug.1 Unknown risk of increased immunologic reaction with repeated administration.1 Immediately discontinue infusion and institute appropriate therapy if an anaphylactoid reaction occurs.1

Specific Populations

Category C.1

Weigh risks against benefits of therapy in pregnant women.1 2 310 311 Some clinicians consider alteplase for ischemic stroke to be contraindicated in pregnant women.a

Not known if distributed in milk; cautious use recommended.1

Safety and efficacy not established with IV alteplase.1 221 However, used with some success in a few infants and children with thrombosis of the vena cava, aorta, or peripheral arteries.286 287 288

Safety and efficacy of intracatheter instillation in neonates, children, and adolescents (2 weeks to 17 years of age) with occluded central venous catheters similar to that in adults.325

Thrombolytic therapy generally not recommended for treatment of venous thromboembolism in neonates and children unless vessel occlusion is life-threatening and/or causes organ dysfunction.1013 If thrombolysis is required, ACCP states that alteplase is the drug of choice; alteplase exhibits greater fibrin specificity, lower immunogenicity, and more effective clot lysis in vitro compared with streptokinase or urokinase (both no longer commercially available in the US).1013

ACCP states that thrombolytic therapy generally not recommended in children with arterial ischemic stroke.1013

Assess risks against the anticipated benefits of therapy in patients >75 years of age.1 2 310 311 Intracranial hemorrhage and other major bleeding complications more common.62 154 156

Limited data in animals suggests possible prolonged elimination half-life of t-PA in patients with severely impaired hepatic function and/or hepatic blood flow.46 185 221 Weigh anticipated benefits against risks of possible hemostatic defects associated with severe hepatic disease.1

Common Adverse Effects

Hemorrhage.1 2 31 32 33 34 36 37 38 39 40 41 43 44 45 46 47 48 154 155 198

(AL te plase)

There are no dosage adjustments provided in the manufacturer’s labeling. Plasma clearance is rapid and mediated primarily by the liver; therefore, degree of renal impairment is unlikely to influence elimination of alteplase. Hemostatic defects due to severe renal disease may increase the risk for bleeding.

Hemodialysis: Dialyzable: Unknown, but unlikely (NCS/SCCM [Frontera 2016])

Ask your doctor before taking aspirin or ibuprofen (Motrin, Advil) shortly after you have received alteplase. These medications can increase your risk of bleeding.

Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• any medication used to prevent blood clots;
• a blood thinner (heparin, warfarin, Coumadin, Jantoven); or
• NSAIDs (nonsteroidal anti-inflammatory drugs)--aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others.

This list is not complete. Other drugs may interact with alteplase, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

More frequently reported side effects include: gastrointestinal hemorrhage and genitourinary tract hemorrhage. See below for a comprehensive list of adverse effects.

0.9 mg/kg (up to 90 mg) IV over 60 minutes with 10% of the total dose administered as an initial IV bolus over the first minute.

Occluded central venous catheter:
Manufacturer's recommendations (CathFlo Activase): Patients 30 or more kg: 2 mg in 2 mL; may instill second dose if catheter remains occluded after 2 hour dwell time. A recent study using escalating doses of 0.5 mg, 1 mg, and 2 mg (60 minute dwell time) found that 86.2% of catheters were cleared with the 0.5 mg dose.

Data not available