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Alteplase: Drug information

Alteplase: Drug information
(For additional information see "Alteplase: Patient drug information" and see "Alteplase: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Activase;
  • Cathflo Activase
Brand Names: Canada
  • Activase RT-PA;
  • Alteplase RT-PA;
  • Cathflo
Pharmacologic Category
  • Thrombolytic Agent
Dosing: Adult
Acute ischemic stroke

Acute ischemic stroke: Note: Perform non–contrast-enhanced CT or MRI and blood glucose check prior to administration. After ensuring eligibility criteria are met, administer as soon as possible within 3 hours (labeled use) or 3 to 4.5 hours (off-label use) of symptom onset (Ref). Symptom onset is usually defined as the time last seen normal or at baseline; however, some stroke centers use imaging-based criteria for select patients who have unknown time of symptom onset (eg, wake-up or unwitnessed stroke) (Ref). Before starting antiplatelet agents or anticoagulation, wait 24 hours after alteplase administration and confirm stroke is stable with no evidence of hemorrhage via a follow-up non-contrast CT (or MRI). The risk of administering antiplatelet or anticoagulant therapy within 24 hours after alteplase is uncertain (Ref).

IV:

Recommended total dose: 0.9 mg/kg (maximum total dose: 90 mg).

Patient weight <100 kg: 0.09 mg/kg (10% of 0.9 mg/kg dose) as an IV bolus over 1 minute, followed by 0.81 mg/kg (90% of 0.9 mg/kg dose) as a continuous infusion over 60 minutes.

Patient weight ≥100 kg: 9 mg (10% of 90 mg) as an IV bolus over 1 minute, followed by 81 mg (90% of 90 mg) as a continuous infusion over 60 minutes.

Catheter occlusion

Catheter occlusion:

Central venous catheter occlusion, clearance:

Intra-catheter:

Patient weight ≥30 kg: 1 or 2 mg; allow to dwell in catheter for 30 minutes to 2 hours; may instill a second dose if catheter remains occluded after 2 hours (Ref).

Hemodialysis catheter occlusion, clearance (off-label use): Note: May use after failure of a forceful saline flush. Total volume (alteplase and saline) for instillation is dependent on hemodialysis catheter lumen volume. Optimal regimens and dwell times have not been identified; refer to institutional protocols.

Intra-hemodialysis catheter:

Short dwell (pre-hemodialysis): Instill 1 to 2 mg per lumen, then instill saline to fill the internal volume; allow to dwell in hemodialysis catheter for 30 minutes to 2 hours, then withdraw; attempt a forceful saline flush; if one or both lumens are still occluded, may instill a second dose (Ref).

Long dwell (post-hemodialysis): Instill 1 to 2 mg per lumen, then instill saline to fill the internal volume; allow to dwell in hemodialysis catheter until next hemodialysis session (Ref).

Peritoneal dialysis catheter occlusion, clearance (off-label use): Note: Total volume (alteplase and sterile water) for instillation is dependent on peritoneal catheter lumen volume and transfer set lumen volume. Optimal regimens and dwell times have not been identified; refer to institutional protocols.

Intra-peritoneal dialysis catheter: Instill 4 to 8 mg into transfer set and peritoneal catheter; allow to dwell for 1 to 2 hours or until next peritoneal dialysis session; aspirate alteplase from catheter lumen using a large syringe or attempt to drain using a dialysate twin bag; then perform a full in-and-out flush (manual exchange) of dialysate to remove any residual alteplase in catheter. May instill a second dose if catheter remains obstructed. When lysis is successful, heparin may be added to dialysate for next several exchanges to help maintain patency (Ref).

Frostbite

Frostbite (off-label use): Note: Patients should be transferred to a facility that is familiar with managing patients with frostbite. May consider in patients with deep frostbite injury who are at high risk for life-altering amputation. Initiate therapy as soon as possible but at least within 24 hours of tissue rewarming. Prior to use, evaluate alteplase contraindications. Anticoagulation may be used in conjunction with thrombolytic therapy, either concurrently or following administration of the thrombolytic, but not as monotherapy (Ref). Optimal regimens, administration routes, and doses, including the use of therapeutic or low-dose anticoagulation after thrombolytic therapy, have not been identified; refer to institutional protocols. Some experts prefer IV administration of thrombolytic since it is effective and more easily administered (Ref).

Example regimens include:

IV: 0.15 mg/kg bolus over 15 minutes, followed by a continuous IV infusion of 0.15 mg/kg/hour for up to 6 hours (total time of infusion duration may be <6 hours if maximum total dose is reached; maximum total dose: 100 mg) (Ref).

Intra-arterial: 2 to 4 mg bolus, followed by a continuous intra-arterial infusion of 0.5 to 1 mg/hour via femoral or brachial artery; if multiple extremity involvement, divide dose between affected extremities. Discontinue if reperfusion is complete (ie, as evidenced by angiography or other imaging) or after infusion duration of 72 hours (Ref).

Mechanical prosthetic valve or bioprosthetic valve thrombosis

Mechanical prosthetic valve or bioprosthetic valve thrombosis (off-label use): Note: Management (ie, thrombolysis, surgery, and/or therapeutic anticoagulation) is individualized based on patient presentation and comorbidities, thrombus location (left- or right-sided valve) and size, clinical expertise, patient preference, and contraindications to thrombolytic therapy (Ref). Optimal regimen and doses have not been identified; refer to institutional protocols.

IV: Hold anticoagulation and when INR <2.5 or aPTT <50 seconds, administer 1 mg/hour continuous infusion for 25 hours (25 mg total); may repeat this dose up to 8 times if there is not adequate resolution of thrombus based on transesophageal echocardiogram (maximum total dose: 200 mg). Between each alteplase dose, administer a 6-hour infusion of heparin titrated to aPTT 1.5 to 2 times control; aPTT should be <50 seconds prior to starting the next dose of alteplase (if necessary) and heparin should not be given during alteplase infusions. Most patients require ≤3 infusions of alteplase (Ref).

Note: After complete thrombus resolution, stop alteplase infusion and initiate heparin infusion or other therapeutic parenteral anticoagulation until warfarin achieves therapeutic INR for 2 consecutive days. If thrombosis occurred while at goal INR, increasing goal INR may be necessary (eg, to goal INR of 3 if prior goal INR was 2.5) (Ref).

Parapneumonic effusions, complicated and empyema

Parapneumonic effusions, complicated and empyema (off-label use): Note: Consider use in patients who do not sufficiently respond to conventional therapy (eg, chest tube drainage and antibiotics) and/or who are not surgical candidates (Ref). Optimal regimen and doses have not been identified; refer to institutional protocols.

Intrapleural: 10 mg once or twice daily for 3 days; used sequentially or concurrently with intrapleural dornase alfa. For sequential dosing, administer alteplase, dwell for ~1 hour and drain for ~1 hour, then administer dornase alfa using the same dwell and drain sequence (Ref). For concurrent dosing, administer alteplase and dornase alfa via 2 separate syringes, followed by a 10 to 60 mL saline flush, dwell for ~1 to 2 hours then drain (Ref).

Peripheral arterial occlusion, acute

Peripheral arterial occlusion, acute (off-label use): Note: Consider thrombolytic use as an alternative to surgery at centers experienced with interventional radiology (Ref). Optimal doses and regimen (including with use of systemic anticoagulation vs localized, low-dose anticoagulation) have not been identified; refer to institutional protocols.

Examples of regimens include:

Intra-arterial: 4 to 10 mg as an initial bolus (administered during intervention), followed by a continuous infusion with a usual dosage range of 0.25 to 2 mg/hour; continue for 2 to 48 hours or until clot resolution (Ref). Some experts follow the initial bolus with a continuous infusion of 1 mg/hour and a simultaneous infusion of localized, low-dose heparin through the side port of the sheath for up to 2 to 3 days (Ref).

Note: Some experts use fibrinogen to guide therapy. If fibrinogen is <150 mg/dL or a drop in fibrinogen is greater than one-half of the previous level, reduce infusion rate by half. If fibrinogen falls to <100 mg/dL, stop infusion for 1 hour, then recheck fibrinogen level and consult with prescribing physician (Ref).

Pulmonary embolism, acute hemodynamically stable

Pulmonary embolism, acute hemodynamically stable (intermediate to high risk [submassive]) (off-label use): Note: For most patients without hypotension, parenteral or oral anticoagulation alone is preferred over thrombolysis and anticoagulation. Systemic thrombolysis may be considered for select, younger patients with low risk of bleeding who deteriorate (eg, progressive increase in heart rate, decrease in blood pressure, signs of shock, worsening gas exchange, progressive right heart dysfunction on echocardiography, increase in cardiac biomarkers) despite parenteral anticoagulation (Ref). Some experts prefer catheter-directed therapy (CDT), when procedural expertise is available, and the patient has a low risk of bleeding; may also consider CDT over systemic thrombolysis in patients with an increased risk of bleeding or with contraindications to systemic thrombolytic therapy (Ref).

IV: 100 mg infused over 2 hours. Institute or resume parenteral anticoagulation near the end of or immediately following the alteplase infusion when aPTT or thrombin time returns to twice normal or less.

Catheter-directed thrombolysis (off-label use): Note: For use at experienced centers; may be performed with ultrasound and catheter-assisted thrombus removal (Ref). Optimal regimens and doses have not been identified; refer to institutional protocols and individualize dose.

Summary of dosing based on prospective clinical trials: Intra-catheter: Low-dose infusion range: 0.5 to 2 mg/hour, continued for 2 to 15 hours; total dose range: 4 to 24 mg depending on whether PE is unilateral or bilateral; resume postprocedural anticoagulation at discretion of clinician (Ref).

Pulmonary embolism, acute hemodynamically unstable

Pulmonary embolism, acute hemodynamically unstable (high risk [massive]): Note: Consider systemic thrombolytic therapy followed by anticoagulation over anticoagulation alone (Ref). Systemic thrombolysis is generally preferred over catheter-directed therapy (CDT) since systemic treatment can be completed more rapidly (Ref). Some experts prefer CDT, when procedural expertise is available, if systemic thrombolysis is contraindicated or in patients with an increased bleeding risk or persistent hemodynamic instability despite systemic thrombolysis (Ref).

IV: 100 mg infused over 2 hours.

Note: Institute or resume parenteral anticoagulation near the end of or immediately following alteplase infusion when aPTT or thrombin time returns to twice normal or less (Ref).

Catheter-directed thrombolysis: (off-label use): Note: For use at experienced centers; may be performed with ultrasound and catheter-assisted thrombus removal (Ref). Optimal regimens and doses have not been identified; refer to institutional protocols and individualize dose.

Summary of dosing based on prospective clinical trials: Intra-catheter: Low-dose infusion range: 0.5 to 2 mg/hour, continued for 2 to 15 hours; total dose range: 4 to 24 mg depending on whether PE is unilateral or bilateral; resume postprocedural anticoagulation at discretion of clinician (Ref).

Pulmonary embolism, associated with cardiac arrest

Pulmonary embolism, associated with cardiac arrest (off-label use): Note: Thrombolytic therapy is not recommended for routine use during cardiopulmonary arrest. May consider on a case-by-case basis (eg, suspected PE-induced cardiac arrest) (Ref).

IV, Intraosseous (if IV access cannot be obtained): Initial: 50 mg bolus over 2 minutes and continue CPR; after 15 minutes, if return of spontaneous circulation is not achieved and medical team decides to continue CPR, repeat 50 mg bolus. In patients with impending cardiac arrest, 50 mg bolus over 2 minutes, followed by a 50 mg infusion over the next 2 hours. Use therapeutic IV anticoagulation in addition to thrombolytic therapy (Ref). Note: When administered via intraosseous catheter, monitor for extravasation and subcutaneous bleeding at the intraosseous catheter insertion site (Ref).

ST-elevation myocardial infarction

ST-elevation myocardial infarction (alternative agent): Note: Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy. Thrombolytic therapy is an option in centers without PCI capability, followed by transfer to a PCI-capable center. Administer thrombolytic therapy within 30 minutes of first medical contact (in ambulance or emergency department) if primary PCI cannot be performed within 120 minutes; if primary PCI is not available, may still consider thrombolysis in patients who present late (within 12 to 24 hours of symptom onset) and have ongoing ischemia or extensive ST elevation. Administer aspirin, clopidogrel, and anticoagulant therapy (ie, unfractionated heparin, enoxaparin, or fondaparinux) in combination with thrombolytic therapy (Ref).

IV:

Patient weight >67 kg: Infuse 15 mg IV bolus over 1 to 2 minutes, followed by infusions of 50 mg over 30 minutes, then 35 mg over 1 hour; maximum total dose: 100 mg.

Patient weight ≤67 kg: Infuse 15 mg IV bolus over 1 to 2 minutes, followed by infusions of 0.75 mg/kg (not to exceed 50 mg) over 30 minutes, then 0.5 mg/kg (not to exceed 35 mg) over 1 hour; maximum total dose: 100 mg.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

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 (Ref)

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling. Plasma clearance is rapid and mediated primarily by the liver. Significant hepatic impairment and hemostatic defects due to severe hepatic disease may increase the risk for bleeding.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Alteplase: Pediatric drug information")

Occluded IV catheter

Occluded IV catheter: Infants, Children, Adolescents: Intracatheter: Dose listed is per lumen; for multilumen catheters, treat one lumen at a time; do not infuse into patient; dose should always be aspirated out of catheter after dwell.

Manufacturer's labeling: Cathflo Activase: Central venous catheter:

Patients <30 kg: Use a 1 mg/mL concentration; instill a volume equal to 110% of the internal lumen volume of the catheter; do not exceed 2 mg in 2 mL; may instill a second dose if catheter remains occluded after 2-hour dwell time.

Patients ≥30 kg: 2 mg in 2 mL; may instill second dose if catheter remains occluded after 2-hour dwell time.

Chest guidelines (Ref): Note: The most recent guidelines (2012) continue to recommend alteplase as a treatment option but specific dosage recommendation is not provided (Ref).

Central venous catheter: Note: Some institutions use lower doses (eg, 0.25 mg/0.5 mL) in infants 1 to <3 months.

Patients ≤10 kg: 0.5 mg diluted in NS to a volume equal to the internal volume of the lumen; instill in lumen over 1 to 2 minutes; leave in lumen for 1 to 2 hours, then aspirate out of catheter, do not infuse into patient; flush catheter with NS.

Patients >10 kg: 1 mg in 1 mL of NS; use a volume equal to the internal volume of the lumen; maximum: 2 mg in 2 mL per lumen; instill in each lumen over 1 to 2 minutes; leave in lumen for 1 to 2 hours; then aspirate out of catheter, do not infuse into patient; flush catheter with NS.

SubQ port:

Patients ≤10 kg: 0.5 mg diluted with NS to 3 mL.

Patients >10 kg: 2 mg diluted with NS to 3 mL.

Systemic thrombosis

Systemic thrombosis: Note: Dose must be titrated to effect. No pediatric studies have compared local to systemic thrombolytic therapy; therefore, there is no evidence to suggest that local infusions are superior. The pediatric patients' small vessel size may increase the chance of local damage to blood vessels and formation of a new thrombus; however, local infusion may be appropriate for catheter-related thromboses if the catheter is already in place (Ref).

Standard dose infusion: Limited data available; optimal dose not established; most published papers consist of case reports; few prospective pediatric studies have been conducted; several studies have used the following doses (Ref): Infants, Children, and Adolescents: Chest 2012 and AHA 2013 recommendations: IV: Usual dose: 0.5 mg/kg/hour for 6 hours; range: 0.1 to 0.6 mg/kg/hour; some patients may require longer or shorter duration of therapy; higher doses may be associated with an increased incidence of serious bleeding (Ref).

Low-dose infusion: Limited data available. Various “low-dose” regimens have been used: Infants, Children, and Adolescents:

AHA 2013 recommendations: IV: 0.03 to 0.06 mg/kg/hour for 12 to 48 hours; maximum hourly dose: 2 mg/hour (Ref).

Additional reported regimens: IV:

Wang 2003: Initial: 0.01 to 0.03 mg/kg/hour; usual effective range: 0.015 to 0.03 mg/kg/hour; duration of therapy based on clinical response; in this study of 17 pediatric patients (1.5 to 18 years) with acute and chronic thrombus, dosing was titrated to effect up to 0.06 mg/kg/hour in children and adolescents; final effective range: 0.007 to 0.06 mg/kg/hour; administration included systemic therapy as well as local infusions directly at site of thrombus (n=4); duration of therapy ranged from 4 to 96 hours. A similar dosing range has been reported in pediatric case reports (Ref).

Leary 2010: Initial: 0.03 to 0.06 mg/kg/hour for 12 to 48 hours; doses were titrated as necessary up to 0.12 mg/kg/hour; dosing from a retrospective study of 23 patients (median age: 12 years, range: 6 months to 21.5 years) diagnosed with DVT; eight patients required a dose increase to 0.12 mg/kg/hour; overall response rate: 59%, with complete clot resolution in 18% and partial resolution in 41%.

Bratincsák 2013: Initial: 0.05 mg/kg/hour for 30 minutes, if no signs of bleeding, rate increased to 0.1 mg/kg/hour; therapy used in 12 children with arterial or femoral vascular occlusions following cardiac catheterization.

Catheter-directed infusion: Limited data available: Children and Adolescents: Intra-arterial, IV (administered through catheter or via catheter with tip placed at anatomic site of clot): 0.025 mg/kg/hour or 0.5 to 2 mg/hour for 12 to 24 hours (Ref).

Parapneumonic effusion

Parapneumonic effusion: Limited data available: Infants >3 months, Children, and Adolescents: Intrapleural:

Fixed dose: 4 mg in 40 mL NS, first dose at time of chest tube placement with 1-hour dwell time, repeat every 24 hours for 3 days (total of 3 doses) (Ref).

Weight-directed: 0.1 mg/kg (maximum: 3 mg) in 10 to 30 mL NS, first dose after chest tube placement, 0.75- to 1-hour dwell time, repeat every 8 hours for 3 days (total of 9 doses) (Ref).

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%: Cardiovascular: Intracranial hemorrhage (CVA: Within 90 days: 15%, within 36 hours: 6%; AMI: <1%)

1% to 10%:

Cerebrovascular accident (new ischemic stroke in CVA: 6%)

Dermatologic: Ecchymosis (AMI: 1%)

Gastrointestinal: Gastrointestinal hemorrhage (AMI: 5%)

Genitourinary: Genitourinary tract hemorrhage (AMI: 4%)

Frequency not defined:

Hematologic & oncologic: Arterial embolism, major hemorrhage, pulmonary embolism

Infection: Sepsis

1%, postmarketing, and/or case reports: Anaphylaxis, angioedema, atrioventricular block, atrioventricular dissociation, cardiac arrhythmia, cardiac failure, cardiac tamponade, cardiogenic shock, cerebral edema, cerebral herniation, deep vein thrombosis, embolism, epistaxis, fever, gingival hemorrhage, hypersensitivity reaction, hypotension, ischemia (recurrent), laryngeal edema, mitral valve insufficiency, myocardial reinfarction, myocardial rupture, nausea, pericardial effusion, pericarditis, pleural effusion, pulmonary edema, retroperitoneal hemorrhage, seizure, skin rash, thromboembolism, urticaria, vomiting

Contraindications

Hypersensitivity to alteplase or any component of the formulation.

Indication-specific contraindications

a Alteplase may be administered to patients whose BP can be safely lowered with antihypertensives to <185/110 mm Hg, with the treating physician assessing for stability of BP prior to administration.

b Alteplase may be administered to patients presenting <3 hours after initial symptoms with mild but disabling stroke symptoms in the opinion of the treating physician. Alteplase is also reasonable in patients presenting <3 hours after initial symptoms with moderate to severe ischemic stroke who demonstrate early improvement but remain moderately impaired and potentially disabled in the examiner's judgment (AHA/ASA [Powers 2019]).

c Alteplase may be administered to patients presenting with initial blood glucose concentrations <50 or >400 mg/dL that are subsequently normalized and are otherwise eligible to receive alteplase (AHA/ASA [Powers 2019]).

d Patients without a history of thrombocytopenia, recent use of oral anticoagulants, or recent use of heparin may receive IV alteplase prior to availability of these laboratory results, but IV alteplase should be discontinued if platelets <100,000/mm3, INR >1.7, aPTT >40 seconds, or PT abnormally elevated according to laboratory standards (AHA/ASA [Powers 2019]).

e Alteplase may be administered to patients taking direct factor Xa inhibitors (eg, rivaroxaban) or direct thrombin inhibitors (eg, dabigatran) when appropriate laboratory tests (eg, aPTT, INR, platelet count, ecarin clotting time, thrombin time, drug-specific direct anti-factor Xa assay) are normal or the patient has not received a dose of these agents for >48 hours (assuming normal renal function) (AHA/ASA [Powers 2019]).

Treatment of ST-elevation myocardial infarction (STEMI) or pulmonary embolism (PE)

Active internal bleeding; history of recent stroke; recent (within 3 months [ACCF/AHA: Within 2 months]) intracranial or intraspinal surgery or serious head trauma; presence of intracranial conditions that may increase the risk of bleeding (eg, intracranial neoplasm, arteriovenous malformation, aneurysm); known bleeding diathesis; severe uncontrolled hypertension (ACCF/AHA: Unresponsive to emergency therapy).

Additional absolute contraindications (ACCF/AHA [O'Gara 2013]; Kearon 2012; Kearon 2016): Active bleeding (excluding menses); any prior intracranial hemorrhage; suspected aortic dissection; ischemic stroke within 3 months except when within 4.5 hours; significant closed head or facial trauma within 3 months with radiographic evidence of bony fracture or brain injury.

Treatment of acute ischemic stroke (AIS)

Current intracranial hemorrhage; subarachnoid hemorrhage; active internal bleeding; recent (within 3 months) intracranial or intraspinal surgery or severe head trauma; presence of intracranial conditions that may increase the risk of bleeding (eg, intracranial neoplasm, arteriovenous malformation, aneurysm); known bleeding diathesis; severe uncontrolled hypertension.a

Additional contraindications (AHA/ASA [Jauch 2013]; AHA/ASA [Powers 2019]): Mild nondisabling stroke (NIH stroke scale score 0 to 5)b; history of intracranial hemorrhage; suspicion of subarachnoid hemorrhage; ischemic stroke within previous 3 months; GI malignancy or bleed within previous 21 days; BP >185 mm Hg systolic or >110 mm Hg diastolica; CT scan showing extensive regions of obvious hypodensity consistent with irreversible injury; symptoms consistent with infective endocarditis; known or suspected aortic arch dissection; intra-axial intracranial neoplasm; blood glucose concentration <50 mg/dLc; coagulopathy (platelets <100,000/mm3, INR >1.7, aPTT >40 seconds, or PT >15 seconds)d; current use of oral anticoagulants with an INR >1.7 or PT >15 seconds, current use of direct factor Xa or thrombin inhibitors with elevated laboratory test results (eg, aPTT, INR, platelets, ecarin clotting time, thrombin time, appropriate anti-factor Xa assay)e; administration of full treatment dose low molecular weight heparin (LMWH) within previous 24 hours; concurrent use with IV aspirin (within 90 minutes) or abciximab.

Note: The AHA/ASA 2019 guidelines have provided updated evidence and recommendations on certain previously ineligible patient groups. For patients presenting in the 3- to 4.5-hour window after initial symptoms, including: Patients >80 years of age (alteplase use in the 3- to 4.5-hour window can be safe and as effective as in younger patients); patients taking warfarin with an INR ≤1.7 (alteplase use appears safe and may be beneficial); patients with a history of both stroke and diabetes (alteplase use may be as effective as treatment in the 0- to 3-hour window, and may be a reasonable option); patients with severe stroke (NIH stroke scale score >25) (benefit is uncertain). For patients with unknown time of symptom onset or who wake up with stroke symptoms, alteplase may be beneficial in those with a diffusion-weighted MRI lesion smaller than one-third of the middle cerebral artery territory and no visible signal change on fluid-attenuated inversion recovery (FLAIR) (AHA/ASA [Powers 2019]).

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Warnings/Precautions

Concerns related to adverse effects:

• Bleeding: Internal bleeding (intracranial, retroperitoneal, gastrointestinal, genitourinary, respiratory) or external bleeding, especially at arterial and venous puncture, sites may occur (may be fatal). The total dose should not exceed 90 mg for acute ischemic stroke or 100 mg for acute myocardial infarction or pulmonary embolism. Doses ≥150 mg associated with significantly increased risk of intracranial hemorrhage compared to doses ≤100 mg. Bleeding risk is low. Monitor all potential bleeding sites; if serious bleeding occurs, the infusion of alteplase and any other concurrent anticoagulants (eg, heparin) should be stopped and the patient should be treated appropriately.

• Cholesterol embolization: Has been reported rarely in patients treated with thrombolytic agents; may present with livedo reticularis, “purple toe” syndrome, acute renal failure, gangrenous digits, hypertension, pancreatitis, myocardial infarction, cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction, or rhabdomyolysis and can be fatal.

• Extravasation: Alteplase may be an irritant; avoid extravasation. Extravasation may result in inflammation or ecchymosis. If extravasation occurs, discontinue infusion at that IV site and apply local therapy.

• Hypersensitivity reactions: Hypersensitivity reactions (eg, anaphylaxis, urticaria, angioedema) have been reported; fatal outcome has been reported (rare). Although typically mild and transient, orolingual angioedema has occurred during and up to 2 hours after alteplase infusion in patients treated for acute ischemic stroke and acute myocardial infarction; the use of concomitant ACE inhibitors, female sex and strokes involving the insular and frontal cortex have been associated with an increased risk (Foster-Goldman 2013; Lin 2014; Pinho 2016). Monitor closely for hypersensitivity reactions during infusion and for several hours after; if signs of hypersensitivity occur or angioedema develops, discontinue the infusion and promptly institute appropriate therapy.

• Thromboembolic events: Use may increase risk of thromboembolic events in patients with high probability of left heart thrombus (eg, patients with mitral stenosis or atrial fibrillation).

Disease-related concerns:

• Conditions that increase bleeding risk: For the following conditions, the risk of bleeding is higher with use of thrombolytics and should be weighed against the benefits of therapy:

• PE: Systolic BP >180 mm Hg or diastolic BP >110 mm Hg; recent bleeding (nonintracranial); recent surgery or invasive procedure; ischemic stroke >3 months previously; anticoagulated (eg, VKA therapy); traumatic CPR; pericarditis or pericardial fluid; diabetic retinopathy; age >75 years of age; low body weight (<60 kg); female; black race (Kearon 2012; Kearon 2016); lumbar puncture within 10 days (ASRA [Horlocker 2012]).

• ST-elevation myocardial infarction (STEMI): History of chronic, severe, poorly controlled hypertension; significant hypertension on presentation (systolic BP >180 mm Hg or diastolic BP >110 mm Hg); history of prior ischemic stroke >3 months; dementia; traumatic or prolonged CPR (>10 minutes); major surgery (<3 weeks); recent internal bleeding (within 2 to 4 weeks); noncompressible vascular punctures; active peptic ulcer; oral anticoagulant therapy (ACCF/AHA [O’Gara 2013]); lumbar puncture within 10 days (ASRA [Horlocker 2012])

• End-stage renal disease: In the treatment of acute ischemic stroke (AIS), according to the American Heart Association/American Stroke Association (AHA/ASA) 2019 guidelines, alteplase use is recommended in patients with end-stage renal disease on hemodialysis who have a normal aPTT (very limited populations evaluated). Patients with an elevated aPTT may have an increased risk for hemorrhagic complications (AHA/ASA [Powers 2019]).

Concurrent drug therapy issues:

• Anticoagulants: Use with caution in patients receiving oral anticoagulants; increased risk of bleeding. In the treatment of STEMI, adjunctive use of parenteral anticoagulants (eg, enoxaparin, heparin, or fondaparinux) is recommended to improve vessel patency and prevent reocclusion and may also contribute to bleeding; monitor for bleeding (ACCF/AHA [O’Gara 2013]).

• Aspirin: In the treatment of acute ischemic stroke, avoid aspirin for 24 hours following administration of alteplase; administration within 24 hours increases the risk of hemorrhagic transformation. According to the AHA/ASA 2019 guidelines, alteplase is recommended for patients taking antiplatelet drug monotherapy or antiplatelet combination therapy (eg, aspirin and clopidogrel) before stroke on the basis that the benefit outweighs a possible small increased risk of symptomatic intracerebral hemorrhage (sICH) (AHA/AHA [Powers 2019]).

• Heparin or low molecular weight heparin: Concurrent heparin anticoagulation may contribute to bleeding. In the treatment of AIS, concurrent use of anticoagulants was not permitted during the initial 24 hours of the <3-hour window trial (NINDS 1995). The AHA/ASA does not recommend initiation of anticoagulant therapy within 24 hours of treatment with alteplase (AHA/ASA [Jauch 2013]). Initiation of SubQ heparin (≤10,000 units) or equivalent doses of low molecular weight heparin for prevention of DVT during the first 24 hours of the 3 to 4.5-hour window trial was permitted and did not increase the incidence of intracerebral hemorrhage (Hacke 2008). Alteplase use is not recommended for acute ischemic stroke in patients who have received a treatment dose of LMWH within the previous 24 hours (AHA/ASA [Powers 2019]). For acute PE, withhold heparin during the 2-hour infusion period.

Special populations:

• Older adult: Use with caution in patients with advanced age (eg, >75 years of age); increased risk of bleeding. In the treatment of pulmonary embolism, >75 years of age is considered a relative contraindication (Kearon 2012; Kearon 2016).

Dosage form specific issues:

• Cathflo Activase: When used to restore catheter function, use Cathflo cautiously in those patients with known or suspected catheter infections. Evaluate catheter for other causes of dysfunction before use. Avoid excessive pressure when instilling into catheter.

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Administration: IM injections should be avoided. Venipunctures should be performed carefully and only when necessary. Avoid internal jugular and subclavian venous punctures. If arterial puncture is necessary, use an upper extremity vessel that can be manually compressed.

• Appropriate use: Alteplase has not been shown to adequately treat underlying deep vein thrombosis in patients with PE. Consider the possible risk of re-embolization due to the lysis of underlying deep venous thrombi in this setting.

Warnings: Additional Pediatric Considerations

Significant bleeding complications including neonatal IVH and hemorrhage requiring PRBC transfusion have been reported in pediatric patients receiving systemic tPA therapy for thrombolysis (Monagle, 2012; Weiner, 1998). Failure of thrombolytic agents in newborns/neonates may occur due to the low plasminogen concentrations (∼50% to 70% of adult levels); supplementing plasminogen (via administration of fresh frozen plasma) may possibly help.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Injection [preservative free]:

Cathflo Activase: 2 mg (1 ea) [contains polysorbate 80]

Solution Reconstituted, Intravenous [preservative free]:

Activase: 50 mg (1 ea); 100 mg (1 ea) [contains polysorbate 80]

Generic Equivalent Available: US

No

Pricing: US

Solution (reconstituted) (Activase Intravenous)

50 mg (per each): $5,280.22

100 mg (per each): $10,560.43

Solution (reconstituted) (Cathflo Activase Injection)

2 mg (per each): $211.61

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Injection:

Cathflo: 2 mg (1 ea)

Solution Reconstituted, Intravenous:

Activase RT-PA: 50 mg (1 ea)

Alteplase RT-PA: 100 mg (1 ea)

Administration: Adult

IV: Activase:

ST-elevation MI or acute ischemic stroke: Administer bolus dose (prepared by one of three methods) over 1 minute followed by an infusion.

Infusion: Remaining dose for STEMI or AIS may be administered as follows: Any quantity of drug not to be administered to the patient must be removed from vial(s) prior to administration of remaining dose.

50 mg vial: Either PVC bag or glass vial and infusion set

100 mg vial: Insert spike end of the infusion set through the same puncture site created by transfer device and infuse from vial.

If further dilution is desired, may be diluted in equal volume of 0.9% sodium chloride or D5W to yield a final concentration of 0.5 mg/mL.

Pulmonary embolism (PE), acute:

Hemodynamically unstable, high-risk (massive) PE or hemodynamically stable, intermediate- to high-risk (submassive) PE (off-label use): Administer as an IV infusion using a peripheral vein (Ref).

PE with cardiac arrest (off-label use): During cardiopulmonary resuscitation, administer as a rapid IV bolus over 2 minutes (Ref). When IV access cannot be established, some experts have suggested administration via intraosseous catheter; must monitor for extravasation and subcutaneous bleeding at the intraosseous catheter insertion site (Ref).

Intracatheter: Cathflo Activase: Instill dose into occluded catheter. Do not force solution into catheter. After a 30-minute dwell time, assess catheter function by attempting to aspirate blood. If catheter is functional, aspirate 4 to 5 mL of blood to remove Cathflo Activase and residual clots. Gently irrigate the catheter with NS. If catheter remains nonfunctional, let Cathflo Activase dwell for another 90 minutes (total dwell time: 120 minutes) and reassess function. If catheter function is not restored, a second dose may be instilled. When used in this fashion, systemic plasma levels are not expected to reach pharmacologic concentrations. If a 2 mg dose was administered into the systemic circulation, the concentration of circulating alteplase would return to endogenous levels within 30 minutes.

Hemodialysis: Total volume (alteplase and saline) for instillation is dependent on hemodialysis catheter lumen volume (Ref).

Peritoneal dialysis: Total volume (alteplase and sterile water) for instillation is dependent on peritoneal catheter lumen volume and transfer set lumen volume; refer to institutional protocols for administration (Ref).

Intrapleural: Parapneumonic effusions, complicated and empyema (off-label use):

Sequential administration: For sequential administration of alteplase and dornase alfa, dilute each dose in 30 to 50 mL NS. Instill alteplase dose into chest tube, followed by a saline flush (eg, 10 to 25 mL), and clamp drain. After ~1 hour dwell time, release clamp and connect chest tube to continuous suction to drain for ~1 hour; then administer dornase alfa with the same flush, dwell, and drain sequence (Ref).

Concurrent administration: For concurrent administration of alteplase and dornase alfa, using separate syringes, dilute alteplase dose in 10 to 50 mL NS. Instill alteplase and dornase alfa into chest tube, one immediately after the other, followed by a 10 to 60 mL NS flush. Clamp drain for ~1 to 2 hours, then drain (Ref).

Administration: Pediatric

Parenteral:

Intracatheter: CathFlo Activase: Instill the appropriate dose into the occluded catheter; do not force solution into catheter; leave in lumen; evaluate catheter function (by attempting to aspirate blood) after 30 minutes; if catheter is functional, aspirate 4 to 5 mL of blood out of catheter in patients ≥10 kg or 3 mL in patients <10 kg to remove drug and residual clot, then gently flush catheter with NS; if catheter is still occluded, leave alteplase in lumen and evaluate catheter function after 120 minutes of dwell time; if catheter is functional, aspirate 4 to 5 mL of blood out of catheter in patients ≥10 kg or 3 mL in patients <10 kg and gently flush with NS; if catheter remains occluded after 120 minutes of dwell time, a second dose may be instilled by repeating the above administration procedure. Discard any unused solution (solution does not contain preservatives).

IV: Activase:

Bolus: Bolus dose may be readied using one of the following methods: 1) Remove bolus dose from reconstituted vial using syringe and needle; for 50 mg vial: Do not prime syringe with air, insert needle into vial stopper; for 100 mg vial, insert needle away from puncture mark created by transfer device; 2) Remove bolus dose from a port on the infusion line after priming; 3) Program an infusion pump to deliver the bolus at the beginning of the infusion. Administer over 1 minute followed by infusion.

Infusion: Total dose for acute pulmonary embolism may be administered as follows: Any quantity of drug not to be administered to the patient must be removed from vial(s) prior to administration of remaining dose.

50 mg vial: Use polyvinyl chloride IV bag or glass vial and infusion set

100 mg vial: Use same puncture site made by transfer device to insert spike end of infusion set and infuse from vial

May also be further diluted in NS or D5W if desired.

Intrapleural: Instill dose into chest tube at time of chest tube placement and clamp drain. Although the optimum dwell time has not been determined, clinical trials more often have used either a 45 minute (Ref) or 1 hour (Ref) dwell time; after dwell period, release clamp and connect chest tube to continuous suction

Usual Infusion Concentrations: Adult

IV infusion: 1 mg/mL

Note: Concentrations for some indications (eg, peripheral arterial occlusion) may require further dilution (eg, 0.1 to 0.2 mg/mL [Chan 2001; Semba 2000]) and a usual concentration may not be established.

Usual Infusion Concentrations: Pediatric

IV infusion: 0.5 mg/mL or 1 mg/mL

Use: Labeled Indications

Activase:

Acute ischemic stroke: Treatment of acute ischemic stroke as soon as possible but within 3 hours of symptom onset.

Pulmonary embolism: Management of acute massive pulmonary embolism.

ST-elevation myocardial infarction: Management of ST-elevation myocardial infarction (STEMI) for the lysis of thrombi in coronary arteries. Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy. Thrombolytic therapy is an option in centers without PCI capability, followed by transfer to a PCI-capable center.

Cathflo Activase:

Central venous catheter occlusion, clearance: Restoration of function to central venous access device.

Use: Off-Label: Adult

Acute ischemic stroke presenting 3 to 4.5 hours after symptom onset; Frostbite; Hemodialysis catheter occlusion, clearance; Mechanical prosthetic valve or bioprosthetic valve thrombosis; Parapneumonic effusions, complicated and empyema; Peripheral arterial occlusion, acute; Peritoneal dialysis catheter occlusion, clearance; Pulmonary embolism, acute (hemodynamically stable, intermediate to high risk [submassive]); Pulmonary embolism associated with cardiac arrest

Medication Safety Issues
Sound-alike/look-alike issues:

Activase may be confused with Cathflo Activase, TNKase

Alteplase may be confused with Altace

“tPA” abbreviation should not be used when ordering this medication; has been mistaken as TNKase (tenecteplase), TPN (total parenteral nutrition), TXA (error-prone abbreviation for tranexamic acid)

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication (IV) among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: May enhance the adverse/toxic effect of Alteplase. Specifically, the risk for angioedema may be increased. Risk C: Monitor therapy

Anticoagulants: Thrombolytic Agents may enhance the anticoagulant effect of Anticoagulants. Management: Monitor for signs and symptoms of bleeding if these agents are combined. For the treatment of acute ischemic stroke, avoidance with anticoagulants is often recommended, see full drug interaction monograph for details. Risk C: Monitor therapy

Aprotinin: May diminish the therapeutic effect of Thrombolytic Agents. Risk C: Monitor therapy

Dabigatran Etexilate: Thrombolytic Agents may enhance the anticoagulant effect of Dabigatran Etexilate. Management: Carefully monitor for bleeding. Dabigatran Canadian labeling recommends avoiding use with thrombolytic agents. Consider avoiding alteplase treatment of acute ischemic stroke in patients receiving dabigatran (see full drug monograph for details). Risk C: Monitor therapy

Defibrotide: May enhance the adverse/toxic effect of Thrombolytic Agents. Specifically, the risk of hemorrhage may be increased. Risk X: Avoid combination

Desirudin: Thrombolytic Agents may enhance the anticoagulant effect of Desirudin. Management: Discontinue treatment with thrombolytic agents prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Risk D: Consider therapy modification

Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Thrombolytic Agents. Bleeding may occur. Risk C: Monitor therapy

Lecanemab: May enhance the adverse/toxic effect of Thrombolytic Agents. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor therapy

Limaprost: May enhance the adverse/toxic effect of Thrombolytic Agents. The risk for bleeding may be increased. Risk C: Monitor therapy

Nitroglycerin: May decrease the serum concentration of Alteplase. Risk C: Monitor therapy

Prostacyclin Analogues: Thrombolytic Agents may enhance the adverse/toxic effect of Prostacyclin Analogues. Specifically, the antiplatelet effects of prostacyclin analogues may lead to an increased risk of bleeding when combined with thrombolytic agents. Risk C: Monitor therapy

Protein C Concentrate (Human): May enhance the adverse/toxic effect of Thrombolytic Agents. Specifically, the risk of bleeding may be increased. Risk C: Monitor therapy

Salicylates: May enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur. Risk C: Monitor therapy

Tranexamic Acid: May diminish the therapeutic effect of Thrombolytic Agents. Thrombolytic Agents may diminish the therapeutic effect of Tranexamic Acid. Risk X: Avoid combination

Pregnancy Considerations

Based on the molecular weight, alteplase is not expected to cross the placenta (Pacheco 2019).

Bleeding may occur with alteplase therapy, and the risk of bleeding complications may be increased in pregnant patients (Alameh 2021; ESC [Regitz-Zagrosek 2018]; Ismail 2017; Merlo 2022).

Case reports describe the use of alteplase in pregnant patients primarily for acute ischemic stroke (Khan 2017; Landais 2018; Rodrigues 2019; Ryman 2019; Sousa Gomes 2019; Watanabe 2019). Use of alteplase may be appropriate for the treatment of moderate or severe acute stroke in pregnant patients. Close monitoring for uterine bleeding is recommended (AHA/ASA [Powers 2019]; Leffert 2016; Pacheco 2019).

Use of alteplase in pregnant patients with pulmonary embolism (ESC [Konstantinides 2020]; Rodriguez 2020) and mechanical prosthetic valve thrombosis (Sousa Gomes 2019) has also been reported. Outcome data related to early postpartum use are limited (Akazawa 2017).

Breastfeeding Considerations

It is not known if alteplase is present in breast milk.

Monitoring Parameters

Acute ischemic stroke (AIS): Baseline: Neurologic examination, head CT (without contrast), blood pressure, CBC, aPTT, PT/INR, glucose. During and after initiation: In addition to monitoring for bleeding complications, the 2019 AHA/ASA guidelines for the early management of AIS recommends the following (AHA/ASA [Powers 2019]):

If severe headache, acute hypertension, nausea, vomiting, or worsening neurological exam occurs, discontinue the infusion and obtain emergency CT scan.

Measure BP and perform neurological assessments every 15 minutes for the first 2 hours of initiation then every 30 minutes for the next 6 hours, then hourly until 24 hours after initiation of alteplase. Increase frequency if a systolic BP is ≥180 mm Hg or if a diastolic BP is ≥105 mm Hg; administer antihypertensive medications to maintain BP at or below these levels.

Obtain a follow-up CT scan at 24 hours before starting anticoagulants or antiplatelet agents.

Central venous catheter clearance: Assess catheter function by attempting to aspirate blood.

Pulmonary embolism: Monitor BP and HR continually and for at least 24 hours after administration; assess invasive catheters hourly for bleeding (Smithburger 2013).

ST-elevation MI: Baseline: Blood pressure, serum cardiac biomarkers, CBC, PT/INR, aPTT. During and after initiation: Assess for evidence of cardiac reperfusion through resolution of chest pain, resolution of baseline ECG changes, preserved left ventricular function, cardiac enzyme washout phenomenon, and/or the appearance of reperfusion arrhythmias; assess for bleeding potential through clinical evidence of GI bleeding, hematuria, gingival bleeding, fibrinogen levels, fibrinogen degradation products, PT and aPTT.

Mechanism of Action

Initiates local fibrinolysis by binding to fibrin in a thrombus (clot) and converts entrapped plasminogen to plasmin

Pharmacokinetics (Adult Data Unless Noted)

Duration: >50% present in plasma cleared ~5 minutes after infusion terminated, ~80% cleared within 10 minutes; fibrinolytic activity persists for up to 1 hour after infusion terminated (Semba 2000)

Distribution: Vd (initial): Approximates plasma volume

Half-life elimination: Initial: 5 minutes

Excretion: Clearance (in patients with acute MI receiving accelerated regimen): Rapidly from circulating plasma (572 ± 132 mL/minute) (Tanswell 1992), primarily hepatic; >50% present in plasma is cleared within 5 minutes after the infusion is terminated, ~80% cleared within 10 minutes (Semba 2000)

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Actilyse;
  • (AR) Argentina: Actilyse;
  • (AT) Austria: Actilyse;
  • (AU) Australia: Actilyse;
  • (BE) Belgium: Actilyse;
  • (BG) Bulgaria: Actilyse;
  • (BR) Brazil: Actilyse;
  • (CH) Switzerland: Actilyse;
  • (CN) China: Actilyse;
  • (CO) Colombia: Actilyse;
  • (CZ) Czech Republic: Actilyse;
  • (DE) Germany: Actilyse | Actilyse cathflo;
  • (EC) Ecuador: Actilyse;
  • (EE) Estonia: Actilyse;
  • (EG) Egypt: Actilyse;
  • (ES) Spain: Actilyse;
  • (FI) Finland: Actilyse;
  • (FR) France: Actilyse;
  • (GB) United Kingdom: Actilyse | Actilyse cathflo;
  • (GR) Greece: Actilyse | Actilyse cathflo;
  • (HK) Hong Kong: Actilyse;
  • (HR) Croatia: Actilyse;
  • (HU) Hungary: Actilyse;
  • (ID) Indonesia: Actilyse;
  • (IE) Ireland: Actilyse | Actilyse cathflo;
  • (IN) India: Actilyse;
  • (IT) Italy: Actilyse | Actiplas;
  • (JO) Jordan: Actilyse;
  • (JP) Japan: Activacin | Grtpa | Grtpa tanabe;
  • (KE) Kenya: Actilyse;
  • (KR) Korea, Republic of: Actilyse;
  • (KW) Kuwait: Actilyse;
  • (LB) Lebanon: Actilyse;
  • (LT) Lithuania: Actilyse | Actilyse cathflo;
  • (LU) Luxembourg: Actilyse;
  • (LV) Latvia: Actilyse | Actilyse cathflo;
  • (MX) Mexico: Actilyse;
  • (MY) Malaysia: Actilyse;
  • (NL) Netherlands: Actilyse;
  • (NO) Norway: Actilyse;
  • (NZ) New Zealand: Actilyse | Actilyse cathflo;
  • (PE) Peru: Actilyse;
  • (PH) Philippines: Actilyse;
  • (PL) Poland: Actilyse;
  • (PR) Puerto Rico: Activase | Cathflo activase;
  • (PT) Portugal: Actilyse;
  • (PY) Paraguay: Actilyse;
  • (QA) Qatar: Actilyse;
  • (RO) Romania: Actilyse;
  • (RU) Russian Federation: Actilyse | Aktilize | Reveliza;
  • (SA) Saudi Arabia: Actilyse;
  • (SE) Sweden: Actilyse;
  • (SG) Singapore: Actilyse;
  • (SI) Slovenia: Actilyse;
  • (SK) Slovakia: Actilyse;
  • (TH) Thailand: Actilyse;
  • (TN) Tunisia: Actilyse;
  • (TR) Turkey: Actilyse;
  • (TW) Taiwan: Actilyse;
  • (UA) Ukraine: Actilyse;
  • (ZA) South Africa: Actilyse
  1. A Comparison of Reteplase With Alteplase for Acute Myocardial Infarction. The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO III) Investigators. N Engl J Med. 1997;337(16):1118-1123. [PubMed 9340503]
  2. Abu-Laban RB, Christenson JM, Innes GD, et al. Tissue plasminogen activator in cardiac arrest with pulseless electrical activity. N Engl J Med. 2002;346(20):1522-1528. [PubMed 12015391]
  3. Activase (alteplase) [prescribing information] South San Francisco, CA: Genentech Inc; September 2022.
  4. Akazawa M, Nishida M. Thrombolysis with intravenous recombinant tissue plasminogen activator during early postpartum period: a review of the literature. Acta Obstet Gynecol Scand. 2017;96(5):529-535. doi:10.1111/aogs.13116 [PubMed 28222238]
  5. Alade SL, Brown RE, Paquet A. Polysorbate 80 and E-Ferol toxicity. Pediatrics. 1986;77(4):593-597. [PubMed 3960626]
  6. Alameh A, Jabri A, Aleyadeh W, et al. Pregnancy-associated myocardial infarction: a review of current practices and guidelines. Curr Cardiol Rep. 2021;23(10):142. doi:10.1007/s11886-021-01579-z [PubMed 34410528]
  7. Alonso-Coello P, Bellmunt S, McGorrian C, et al. Antithrombotic therapy in peripheral artery disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2)(suppl):e669S-e690S. doi:10.1378/chest.11-2307 [PubMed 22315275]
  8. American College of Emergency Physicians Clinical Policies Subcommittee (Writing Committee) on Use of Intravenous tPA for Ischemic Stroke; Brown MD, Burton JH, Nazarian DJ, Promes SB. Clinical policy: use of intravenous tissue plasminogen activator for the management of acute ischemic stroke in the emergency department. Ann Emerg Med. 2015;66(3):322-333.e31. doi:10.1016/j.annemergmed.2015.06.031 [PubMed 26304253]
  9. Anderson B, Urs P, Tudehope D, et al. The Use of Recombinant Tissue Plasminogen Activator in the Management of Infective Intracardiac Thrombi in Pre-term Infants With Thrombocytopaenia. J Paediatr Child Health. 2009;45(10):598-601. [PubMed 19825023]
  10. Anderson BJ, Keeley SR, Johnson ND. Caval Thrombolysis in Neonates Using Low Doses of Recombinant Human Tissue-Type Plasminogen Activator. Anaesth Intensive Care. 1991;19(1):22-27. [PubMed 1901463]
  11. BC Provincial Renal Agency (BCPRA). Alteplase (Cathflo) administration for occluded peritoneal dialysis catheter. http://www.bcrenalagency.ca/resource-gallery/Documents/Alteplase%20(Cathflo%C2%AE)%20Administration%20for%20Occluded%20Peritoneal%20Dialysis%20Catheter.pdf. Published November 2018.
  12. BC Provincial Renal Agency (BCPRA). Provincial standards and guidelines: alteplase use for occluded hemodialysis catheters. http://www.bcrenal.ca/resource-gallery/Documents/Alteplase%20Use%20for%20Occluded%20Hemodialysis%20Catheters.pdf. Published May 2017.
  13. Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, Schonewille WJ; MR CLEAN Investigators, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372(1):11-20. doi:10.1056/NEJMoa1411587 [PubMed 25517348]
  14. Böttiger BW, Bode C, Kern S, et al. Efficacy and safety of thrombolytic therapy after initially unsuccessful cardiopulmonary resuscitation: a prospective clinical trial. Lancet. 2001;357(9268):1583-1585. doi:10.1016/S0140-6736(00)04726-7 [PubMed 11377646]
  15. Bradley JS, Byington CL, Shah SS, et al. The Management of Community-Acquired Pneumonia in Infants and Children Older Than 3 Months of Age: Clinical Practice Guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):e25-e76. [PubMed 21880587]
  16. Bratincsák A, Moore JW, El-Said HG. Low dose tissue plasminogen activator treatment for vascular thrombosis following cardiac catheterization in children: a single center experience. Catheter Cardiovasc Interv. 2013;82(5):782-785.
  17. Bruen KJ, Ballard JR, Morris SE, Cochran A, Edelman LS, Saffle JR. Reduction of the incidence of amputation in frostbite injury with thrombolytic therapy. Arch Surg. 2007;142(6):546-551 [PubMed 17576891]
  18. Cathflo Activase (alteplase) [prescribing information] South San Francisco, CA: Genentech Inc; February 2019.
  19. Cauchy E, Cheguillaume B, Chetaille E. A controlled trial of a prostacyclin and rt-PA in the treatment of severe frostbite. N Engl J Med. 2011;364(2):189-190. [PubMed 21226604]
  20. Centers for Disease Control (CDC). Unusual syndrome with fatalities among premature infants: association with a new intravenous vitamin E product. MMWR Morb Mortal Wkly Rep. 1984;33(14):198-199. http://www.cdc.gov/mmwr/preview/mmwrhtml/00000319.htm [PubMed 6423951]
  21. Chan J, Rees CR, Song AK, et al. Usefulness of Catheter-Directed Thrombolysis Using Alteplase in Peripheral Vascular Occlusion. Proc (Bayl Univ Med Cent). 2001;14(1):3-7. [PubMed 16369579]
  22. Christoforidis GA, Slivka A, Mohammad Y, Karakasis C, Kontzialis M, Khadir M. Reperfusion rates following intra-arterial thrombolysis for acute ischemic stroke: the influence of the method for alteplase delivery. AJNR Am J Neuroradiol. 2012;33(7):1292-1298. [PubMed 22345500]
  23. Colice GL, Curtis A, Deslauriers J, et al. Medical and surgical treatment of parapneumonic effusions: an evidence-based guideline. Chest. 2000;118(4):1158-1171. doi:10.1378/chest.118.4.1158 [PubMed 11035692]
  24. Comerota AJ, Schmieder FA. Intraoperative Lytic Therapy: Agents and Methods of Administration. Semin Vasc Surg. 2001;14(2):132-142. [PubMed 11400089]
  25. Davis SN, Vermeulen L, Banton J, et al. Activity and Dosage of Alteplase Dilution for Clearing Occlusions of Venous-Access Devices. Am J Health Syst Pharm. 2000;57(11):1039-1045. [PubMed 10876745]
  26. Demaerschalk BM, Kleindorfer DO, Adeoye OM, Demchuk AM, Fugate JE, Grotta JC, Khalessi AA, Levy EI, Palesch YY, Prabhakaran S, Saposnik G, Saver JL, Smith EE; American Heart Association Stroke Council and Council on Epidemiology and Prevention. Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke: A Statement for Healthcare Professionals from the American Heart Association/American Stroke Association [published correction appears in Stroke. 2016;47(11):e262]. Stroke. 2016;47(2): 581-641. doi: 10.1161/STR.0000000000000086. [PubMed 26696642]
  27. Disini L, Wilson P, Cockburn JF. Successful intra-arterial alteplase infusion is a predictor of 12-month limb survival in patients with lower limb arterial occlusion. Clin Radiol. 2008;63(6):636-641. [PubMed 18455554]
  28. Doyle E, Britto J, Freeman J, et al. Thrombolysis With Low Dose Tissue Plasminogen Activator. Arch Dis Child. 1992;67(12):1483-1484. [PubMed 1489229]
  29. Er F, Nia AM, Gassanov N, Caglayan E, Erdmann E, Hoppe UC. Impact of rescue-thrombolysis during cardiopulmonary resuscitation in patients with pulmonary embolism. PLoS One. 2009;4(12):e8323. doi:10.1371/journal.pone.0008323 [PubMed 20016808]
  30. Farnoux C, Camard O, Pinquier D, et al. Recombinant Tissue-Type Plasminogen Activator Therapy of Thrombosis in 16 Neonates. J Pediatr. 1998;133(1):137-140. [PubMed 9672527]
  31. Field JM, Hazinski MF, Sayre MR, et al. Part 1: Executive Summary: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122(18)(suppl 3):640-656. [PubMed 20956217]
  32. Fink JM, Capozzi DL, Shermock KM, et al. Alteplase for central catheter clearance: 1 mg/mL versus 2 mg/2 mL. Ann Pharmacother. 2004;38(2):351-352. doi:10.1345/aph.1D004 [PubMed 14742778]
  33. Foster-Goldman A, McCarthy D. Angioedema from recombinant TPA administration: case report and pathophysiology review. Am J Ther. 2013;20(6):691-693. [PubMed 24247033]
  34. Frazin BS. Maximal Dilution of Activase. Am J Hosp Pharm. 1990;47(5):1016. [PubMed 2110773]
  35. Frontera JA, Lewin JJ 3rd, Rabinstein AA, et al; Guideline for reversal of antithrombotics in intracranial hemorrhage: a statement for healthcare professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care. 2016;24(1):6-46. [PubMed 26714677]
  36. Generali J, Cada DJ. Alteplase (t-PA) Bolus: Occluded Catheters. Hospital Pharmacy. 2001;36(1):93-103.
  37. Giglia TM, Massicotte MP, Tweddell JS, et al. Prevention and treatment of thrombosis in pediatric and congenital heart disease: a scientific statement from the American Heart Association. Circulation. 2013;128(24):2622-2703. [PubMed 24226806]
  38. Golper TA, Ponce T. Use of peritoneal dialysis (PD) for the treatment of acute kidney injury (AKI) in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 18, 2020.
  39. Gonzaga T, Jenabzadeh K, Anderson CP, Mohr WJ, Endorf FW, Ahrenholz DH. Use of intra-arterial thrombolytic therapy for acute treatment of frostbite in 62 patients with review of thrombolytic therapy in frostbite. J Burn Care Res. 2016;37(4):e323-e334. doi:10.1097/BCR.0000000000000245 [PubMed 25950290]
  40. Grip O, Kuoppala M, Acosta S, Wanhainen A, Åkeson J, Björck M. Outcome and complications after intra-arterial thrombolysis for lower limb ischaemia with or without continuous heparin infusion. Br J Surg. 2014;101(9):1105-1112. doi:10.1002/bjs.9579 [PubMed 24965149]
  41. Hacke W, Kaste M, Bluhmki E, et al; ECASS Investigators. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317-1329. [PubMed 18815396]
  42. Hartmann J, Hussein A, Trowitzsch E, et al. Treatment of Neonatal Thrombus Formation With Recombinant Tissue Plasminogen Activator: Six Years Experience and Review of the Literature. Arch Dis Child Fetal Neonatal Ed. 2001;85(1):F18-F22. [PubMed 11420316]
  43. Hawkins JA, Scaife ES, Hillman ND, et al. Current Treatment of Pediatric Empyema. Semin Thorac Cardiovasc Surg. 2004;16(3):196-200. [PubMed 15619185]
  44. Hickey S, Whitson A, Jones L, et al. Guidelines for thrombolytic therapy for frostbite. J Burn Care Res. 2020;41(1):176-183. doi:10.1093/jbcr/irz148 [PubMed 31899512]
  45. Horlocker TT, Wedel DJ, Rowlingson JC, et al. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Third Edition). Reg Anesth Pain Med. 2010;35(1):64-101. [PubMed 20052816]
  46. Ibanez B, James S, Agewall S, et al; ESC Scientific Document Group. 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the Management of Acute Myocardial Infarction in Patients Presenting With ST-segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39(2):119-177. doi:10.1093/eurheartj/ehx393 [PubMed 28886621]
  47. Ibrahim AE, Goverman J, Sarhane KA, Donofrio J, Walker TG, Fagan SP. The emerging role of tissue plasminogen activator in the management of severe frostbite. J Burn Care Res. 2015;36(2):e62-e66. doi:10.1097/BCR.0000000000000135 [PubMed 25687362]
  48. Isaksson M, Jansson L. Contact allergy to Tween 80 in an inhalation suspension. Contact Dermatitis. 2002;47(5):312-313. [PubMed 12534540]
  49. Ismail S, Wong C, Rajan P, Vidovich MI. ST-elevation acute myocardial infarction in pregnancy: 2016 update. Clin Cardiol. 2017;40(6):399-406. doi:10.1002/clc.22655 [PubMed 28191905]
  50. Janata K, Holzer M, Kürkciyan I, et al. Major bleeding complications in cardiopulmonary resuscitation: the place of thrombolytic therapy in cardiac arrest due to massive pulmonary embolism. Resuscitation. 2003;57(1):49-55. [PubMed 12668299]
  51. Jauch EC, Saver JL, Adams HP Jr, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2013;44(3):870-947. [PubMed 23370205]
  52. Jiang C, Xie M, Cervellione K, Thurm C. Clinical efficacy and bleeding outcomes of tissue plasminogen activator and dornase alfa in pleural space infection with once daily concurrent administration: a retrospective cohort study. BMC Res Notes. 2020;13(1):368. doi:10.1186/s13104-020-05210-2 [PubMed 32746902]
  53. Johnson AR, Jensen HL, Peltier G, DelaCruz E. Efficacy of intravenous tissue plasminogen activator in frostbite patients and presentation of a treatment protocol for frostbite patients. Foot Ankle Spec. 2011;4(6):344-348. doi:10.1177/1938640011422596 [PubMed 21965579]
  54. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2)(suppl):e419S-e496S. doi:10.1378/chest.11-2301 [PubMed 22315268]
  55. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149(2):315-352. doi:10.1016/j.chest.2015.11.026 [PubMed 26867832]
  56. Khan A, Hosseini P, Nevajda B, Khan S. Lesson of the month 2: use of thrombolysis for ischaemic stroke in pregnancy - a case report and review of literature. Clin Med (Lond). 2017;17(6):581-583. doi:10.7861/clinmedicine.17-6-581 [PubMed 29196364]
  57. Konstantinides S, Geibel A, Heusel G, et al. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med. 2002;347(15):1143-1150. [PubMed 12374874]
  58. Konstantinides SV, Meyer G, Becattini C, et al; ESC Scientific Document Group. 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41(4):543-603. doi:10.1093/eurheartj/ehz405 [PubMed 31504429]
  59. Kucher N, Boekstegers P, Müller OJ, et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation. 2014;129(4):479-486. doi:10.1161/CIRCULATIONAHA.113.005544 [PubMed 24226805]
  60. Kuo WT, Banerjee A, Kim PS, et al. Pulmonary Embolism Response to Fragmentation, Embolectomy, and Catheter Thrombolysis (PERFECT): Initial results from a prospective multicenter registry. Chest. 2015;148(3):667-673. doi:10.1378/chest.15-0119 [PubMed 25856269]
  61. Kürkciyan I, Meron G, Sterz F, et al. Pulmonary embolism as a cause of cardiac arrest: presentation and outcome. Arch Intern Med. 2000;160(10):1529-1535. [PubMed 10826469]
  62. Landais A, Chaumont H, Dellis R. Thrombolytic therapy of acute ischemic stroke during early pregnancy. J Stroke Cerebrovasc Dis. 2018;27(2):e20-e23. doi:10.1016/j.jstrokecerebrovasdis.2016.12.010 [PubMed 29191741]
  63. Landy C, Plancade D, Gagnon N, Schaeffer E, Nadaud J, Favier JC. Complication of intraosseous administration of systemic fibrinolysis for a massive pulmonary embolism with cardiac arrest. Resuscitation. 2012;83(6):e149-e150. doi:10.1016/j.resuscitation.2012.01.044 [PubMed 22394696]
  64. Lavonas EJ, Drennan IR, Gabrielli A, et al. Part 10: Special circumstances of resuscitation: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015;132(18)(suppl 2):S501-S518. doi:10.1161/CIR.0000000000000264 [PubMed 26472998]
  65. Leary SE, Harrod VL, de Alarcon PA, Reiss UM. Low-dose systemic thrombolytic therapy for deep vein thrombosis in pediatric patients. J Pediatr Hematol Oncol. 2010;32(2):97-102. [PubMed 20118811]
  66. Lederer W, Lichtenberger C, Pechlaner C, Kroesen G, Baubin M. Recombinant tissue plasminogen activator during cardiopulmonary resuscitation in 108 patients with out-of-hospital cardiac arrest. Resuscitation. 2001;50(1):71-76. [PubMed 11719132]
  67. Leffert LR, Clancy CR, Bateman BT, et al. Treatment patterns and short-term outcomes in ischemic stroke in pregnancy or postpartum period. Am J Obstet Gynecol. 2016;214(6):723.e1-723.e11. doi:10.1016/j.ajog.2015.12.016 [PubMed 26709084]
  68. Levy M, Benson LN, Burrows PE, et al. Tissue Plasminogen Activator for the Treatment of Thromboembolism in Infants and Children. J Pediatr. 1991;118(3):467-472. [PubMed 1900334]
  69. Lin SY, Tang SC, Tsai LK, et al. Orolingual angioedema after alteplase therapy of acute ischaemic stroke: incidence and risk of prior angiotensin-converting enzyme inhibitor use. Eur J Neurol. 2014;21(10):1285-1291. doi:10.1111/ene.12472 [PubMed 24909847]
  70. Logan JK, Pantle H, Huiras P, Bessman E, Bright L. Evidence-based diagnosis and thrombolytic treatment of cardiac arrest or periarrest due to suspected pulmonary embolism. Am J Emerg Med. 2014;32(7):789-796. doi:10.1016/j.ajem.2014.04.032 [PubMed 24856738]
  71. Lok CE, Huber TS, Lee T, et al; National Kidney Foundation. KDOQI clinical practice guideline for vascular access: 2019 update. Am J Kidney Dis. 2020;75(4)(suppl 2):S1-S164. doi:10.1053/j.ajkd.2019.12.001 [PubMed 32778223]
  72. Lucente P, Iorizzo M, Pazzaglia M. Contact sensitivity to Tween 80 in a child. Contact Dermatitis. 2000;43(3):172. [PubMed 10985636]
  73. Majid A, Kheir F, Folch A, et al. Concurrent intrapleural instillation of tissue plasminogen activator and DNase for pleural infection. A single-center experience. Ann Am Thorac Soc. 2016;13(9):1512-1518. doi:10.1513/AnnalsATS.201602-127OC [PubMed 27333122]
  74. McFarland GE, Aucoin VJ. Intra-arterial thrombolytic therapy for the management of acute limb ischemia. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 8, 2022.
  75. McIntosh SE, Freer L, Grissom CK, et al. Wilderness Medical Society clinical practice guidelines for the prevention and treatment of frostbite: 2019 update. Wilderness Environ Med. 2019;30(4S):S19-S32. [PubMed 31326282]
  76. Merlo AC, Rosa GM, Porto I. Pregnancy-related acute myocardial infarction: a review of the recent literature. Clin Res Cardiol. 2022;111(7):723-731. doi:10.1007/s00392-021-01937-5 [PubMed 34510263]
  77. Meyerovitz MF, Goldhaber SZ, Reagan K, et al. Recombinant tissue-type plasminogen activator versus urokinase in peripheral arterial and graft occlusions: a randomized trial. Radiology. 1990;175(1):75-78. doi:10.1148/radiology.175.1.2107563 [PubMed 2107563]
  78. Monagle P, Chalmers E, Chan A, et al. Antithrombotic Therapy in Neonates and Children: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest, 2008;133(6)(suppl):887S-968S. [PubMed 18574281]
  79. Monagle P, Chan A, Goldenberg NA, et al. Antithrombotic therapy in neonates and children: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, 9th Edition. Chest. 2012;141(2)(suppl):e737-e801. [PubMed 22315277]
  80. Nowak-Gottl U, Auberger K, Halimeh S, et al. Thrombolysis in Newborns and Infants. Thromb Haemost. 1999;82(suppl 1):112-116. [PubMed 10695499]
  81. Nygaard RM, Lacey AM, Lemere A, et al. Time matters in severe frostbite: assessment of limb/digit salvage on the individual patient level. J Burn Care Res. 2017;38(1):53-59. doi:10.1097/BCR.0000000000000426 [PubMed 27606554]
  82. O'Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127(4):e362-e425. [PubMed 23247304]
  83. Oliveira-Filho J, Mullen MT. Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 10, 2022.
  84. Ortel TL, Neumann I, Ageno W, et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Adv. 2020;4(19):4693-4738. doi:10.1182/bloodadvances.2020001830 [PubMed 33007077]
  85. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines. Circulation. 2021;143(5):e72-e227. doi:10.1161/CIR.0000000000000923 [PubMed 33332150]
  86. Özkan M, Çakal B, Karakoyun S, et al. Thrombolytic therapy for the treatment of prosthetic heart valve thrombosis in pregnancy with low-dose, slow infusion of tissue-type plasminogen activator. Circulation. 2013a;128(5):532-540. doi:10.1161/CIRCULATIONAHA.113.001145 [PubMed 23812180]
  87. Özkan M, Gündüz S, Biteker M, et al. Comparison of different TEE-guided thrombolytic regimens for prosthetic valve thrombosis: the TROIA trial. JACC Cardiovasc Imaging. 2013b;6(2):206-216. doi:10.1016/j.jcmg.2012.10.016 [PubMed 23489534]
  88. Özkan M, Gündüz S, Gürsoy OM, et al. Ultraslow thrombolytic therapy: A novel strategy in the management of PROsthetic MEchanical valve Thrombosis and the prEdictors of outcomE: The Ultra-slow PROMETEE trial. Am Heart J. 2015;170(2):409-418. doi:10.1016/j.ahj.2015.04.025 [PubMed 26299240]
  89. Pacheco LD, Hankins GDV, Saad AF, Saade GR. Acute management of ischemic stroke during pregnancy. Obstet Gynecol. 2019;133(5):933-939. doi:10.1097/AOG.0000000000003220 [PubMed 30969218]
  90. Paine RE, Turner EN, Kloda D, Falank C, Chung B, Carter DW. Protocoled thrombolytic therapy for frostbite improves phalangeal salvage rates. Burns Trauma. 2020;8:tkaa008. doi:10.1093/burnst/tkaa008 [PubMed 32341921]
  91. Panchal AR, Bartos JA, Cabañas JG, et al; Adult Basic and Advanced Life Support Writing Group. Part 3: Adult basic and advanced life support: 2020 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2020;142(16)(suppl_2):S366-S468. doi:10.1161/CIR.0000000000000916 [PubMed 33081529]
  92. Piazza G, Hohlfelder B, Jaff MR, et al; SEATTLE II Investigators. A prospective, single-arm, multicenter trial of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis for acute massive and submassive pulmonary embolism: the SEATTLE II Study. JACC Cardiovasc Interv. 2015;8(10):1382-1392. doi:10.1016/j.jcin.2015.04.020 [PubMed 26315743]
  93. Piccolo F, Pitman N, Bhatnagar R, et al. Intrapleural tissue plasminogen activator and deoxyribonuclease for pleural infection. An effective and safe alternative to surgery. Ann Am Thorac Soc. 2014;11(9):1419-1425. [PubMed 25296241]
  94. Pinho J, Alves JN, Oliveira L, et al. Orolingual angioedema after thrombolysis is not associated with insular cortex ischemia on pre-thrombolysis CT. J Neurol Sci. 2016;369:48-50. doi:10.1016/j.jns.2016.07.043 [PubMed 27653864]
  95. Pislaru S, Connolly HM. Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Management. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 5, 2022b.
  96. Pislaru S, Connolly HM. Management of mechanical prosthetic valve thrombosis and obstruction. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 5, 2022a.
  97. Poncyljusz W, Falkowski A, Kojder I, et al. Treatment of acute ischemic brain infarction with the assistance of local intraarterial thrombolysis with recombinant tissue-type plasminogen activator. Acta Radiol. 2007;48(7):774-780. [PubMed 17729010]
  98. Powers WJ, Derdeyn CP, Biller J, Coffey CS, Hoh BL, Jauch EC, Johnston KC; American Heart Association Stroke Council, et al. 2015 American Heart Association/American Stroke Association Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2015;46(10):3020-35. doi:10.1161/STR.0000000000000074 [PubMed 29367334]
  99. Powers WJ, Rabinstein AA, Ackerson T, et al; American Heart Association Stroke Council. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46-e110. doi:10.1161/STR.0000000000000158 [PubMed 26123479]
  100. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019;50(12):e344-e418. doi:10.1161/STR.0000000000000211 [PubMed 31662037]
  101. Rahman NM, Maskell NA, West A, et al. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med. 2011;365(6):518-526. doi:10.1056/NEJMoa1012740 [PubMed 21830966]
  102. Refer to manufacturer's labeling.
  103. Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, et al; ESC Scientific Document Group. 2018 ESC guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J. 2018;39(34):3165-3241. doi:10.1093/eurheartj/ehy340 [PubMed 30165544]
  104. Rivera-Lebron B, Weinberg AS. Approach to thrombolytic (fibrinolytic) therapy in acute pulmonary embolism: patient selection and administration. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 11, 2023.
  105. Rodriguez D, Jerjes-Sanchez C, Fonseca S, et al. Thrombolysis in massive and submassive pulmonary embolism during pregnancy and the puerperium: a systematic review. J Thromb Thrombolysis. 2020;50(4):929-941. doi:10.1007/s11239-020-02122-7 [PubMed 32347509]
  106. Rodrigues R, Silva R, Fontão L, Ruano L, Roriz JM. Acute ischemic stroke in pregnancy. Case Rep Neurol. 2019;11(1):37-40. doi:10.1159/000496386 [PubMed 31543784]
  107. Roudaut R, Lafitte S, Roudaut MF, et al. Fibrinolysis of mechanical prosthetic valve thrombosis: a single-center study of 127 cases. J Am Coll Cardiol. 2003;41(4):653-658. [PubMed 12598078]
  108. Ryman KM, Pace WD, Smith S, Fontaine GV. Alteplase therapy for acute ischemic stroke in pregnancy: two case reports and a systematic review of the literature. Pharmacotherapy. 2019;39(7):767-774. doi:10.1002/phar.2278 [PubMed 31077601]
  109. Schweizer J, Altmann E, Stösslein F, Florek HJ, Kaulen R. Comparison of tissue plasminogen activator and urokinase in the local infiltration thrombolysis of peripheral arterial occlusions. Eur J Radiol. 1996;22(2):129-132. doi:10.1016/0720-048x(96)00742-5 [PubMed 8793432]
  110. Semba CP, Bakal CW, Calis KA, et al. Alteplase as an alternative to urokinase. Advisory Panel on Catheter-Directed Thrombolytic Therapy. J Vasc Interv Radiol. 2000;11(3):279-287. [PubMed 10735420]
  111. Sharifi M, Berger J, Beeston P, Bay C, Vajo Z, Javadpoor S; "PEAPETT" investigators. Pulseless electrical activity in pulmonary embolism treated with thrombolysis (from the "PEAPETT" study). Am J Emerg Med. 2016;34(10):1963-1967. doi:10.1016/j.ajem.2016.06.094 [PubMed 27422214]
  112. Shelley WB, Talanin N, Shelley ED. Polysorbate 80 hypersensitivity. Lancet. 1995;345(8980):1312-1313. [PubMed 7746084]
  113. Smithburger PL, Campbell S, Kane-Gill SL. Alteplase treatment of acute pulmonary embolism in the intensive care unit. Crit Care Nurse. 2013;33(2):17-27. [PubMed 23547122]
  114. Sousa Gomes M, Guimarães M, Montenegro N. Thrombolysis in pregnancy: a literature review. J Matern Fetal Neonatal Med. 2019;32(14):2418-2428. doi:10.1080/14767058.2018.1434141 [PubMed 29378443]
  115. Soylu H, Brandão LR, Lee KS. Efficacy of Local Instillation of Recombinant Tissue Plasminogen Activator for Restoring Occluded Central Venous Catheters in Neonates. J Pediatr. 2010;156(2):197-201. [PubMed 19969306]
  116. St Peter SD, Tsao, K, Harrison C, et al. Thorascopic Decortication vs Tube Thoracostomy With Fibrinolysis for Empyema in Children: A Prospective, Randomized Trial. J Pediatr Surg. 2009;44(1):106-111. [PubMed 19159726]
  117. Stevens SM, Woller SC, Kreuziger LB, et al. Antithrombotic therapy for VTE disease: second update of the CHEST guideline and expert panel report. Chest. 2021;160(6):e545-e608. doi:10.1016/j.chest.2021.07.055 [PubMed 34352278]
  118. Tanswell P, Tebbe U, Neuhaus K, et al. Pharmacokinetics and fibrin specificity of alteplase during accelerated infusions in acute myocardial infarction. J Am Coll Cardiol. 1992;19(5):1071-1075. [PubMed 1372625]
  119. Tapson VF, Sterling K, Jones N, et al. A randomized trial of the optimum duration of acoustic pulse thrombolysis procedure in acute intermediate-risk pulmonary embolism: the OPTALYSE PE trial. JACC Cardiovasc Interv. 2018;11(14):1401-1410. doi:10.1016/j.jcin.2018.04.008 [PubMed 30025734]
  120. The Gusto Angiographic Investigators. The Effects of Tissue Plasminogen Activator, Streptokinase, or Both on Coronary-Artery Patency, Ventricular Function, and Survival After Acute Myocardial Infarction. N Engl J Med. 1993;329(22):1615-1622. [PubMed 8232430]
  121. Thomalla G, Simonsen CZ, Boutitie F, et al; WAKE-UP Investigators. MRI-guided thrombolysis for stroke with unknown time of onset. N Engl J Med. 2018;379(7):611-622. doi:10.1056/NEJMoa1804355 [PubMed 29766770]
  122. Thrombolysis in the Management of Lower Limb Peripheral Arterial Occlusion - A Consensus Document. Working Party on Thrombolysis in the Management of Limb Ischemia. J Vasc Interv Radiol. 2003;14(9, pt 2):337-349. [PubMed 14514841]
  123. Tissue Plasminogen Activator for Acute Ischemic Stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995;333(24):1581-1587. [PubMed 7477192]
  124. Tountopoulou A, Ahl B, Weissenborn K, Becker H, Goetz F. Intra-arterial thrombolysis using rt-PA in patients with acute stroke due to vessel occlusion of anterior and/or posterior cerebral circulation. Neuroradiology. 2008;50(1):75-83. [PubMed 17917723]
  125. Tsivgoulis G, Katsanos AH, Malhotra K, et al. Thrombolysis for acute ischemic stroke in the unwitnessed or extended therapeutic time window. Neurology. 2020;94(12):e1241-e1248. doi:10.1212/WNL.0000000000008904 [PubMed 31892636]
  126. Vanden Hoek TL, Morrison LJ, Shuster M, et al. Part 12: Cardiac Arrest in Special Situations: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122(18)(suppl 3):829-861. [PubMed 20956228]
  127. Vedantham S, Goldhaber SZ, Julian JA, et al; ATTRACT Trial Investigators. Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis. N Engl J Med. 2017;377(23):2240-2252. doi:10.1056/NEJMoa1615066 [PubMed 29211671]
  128. Wang M, Hays T, Balasa V, et al. Low-dose tissue plasminogen activator thrombolysis in children. J Pediatr Hematol Oncol. 2003;25(5):379-386. [PubMed 12759624]
  129. Watanabe TT, Ichijo M, Kamata T. Uneventful pregnancy and delivery after thrombolysis plus thrombectomy for acute ischemic stroke: case study and literature review. J Stroke Cerebrovasc Dis. 2019;28(1):70-75. doi:10.1016/j.jstrokecerebrovasdis.2018.09.002 [PubMed 30268366]
  130. Weiner GM, Castle VP, DiPietro MA, et al. Successful Treatment of Neonatal Arterial Thromboses With Recombinant Tissue Plasminogen Activator. J Pediatr. 1998;133(1):133-136. [PubMed 9672526]
  131. Whigham CJ, Lindsey JI, Goodman CJ, Fisher RG. Venous port salvage utilizing low dose tPA. Cardiovasc Intervent Radiol. 2002;25(6):513-516. doi:10.1007/s00270-002-2615-4 [PubMed 12391517]
  132. You JJ, Singer DE, Howard PA, et al. Antithrombotic therapy for atrial fibrillation: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2)(suppl):e531S-e575S. doi:10.1378/chest.11-2304 [PubMed 22315271]
  133. Zafren K, Mechem CC. Frostbite: emergency care and prevention. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 15, 2022.
  134. Zorzanello MM, Fleming WJ, Prowant BE. Use of tissue plasminogen activator in peritoneal dialysis catheters: a literature review and one center's experience. Nephrol Nurs J. 2004;31(5):534-537. [PubMed 15518255]
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