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Alteplase: Drug information

Alteplase: Drug information
2024© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Alteplase: Patient drug information" and "Alteplase: Pediatric drug information"

For abbreviations, symbols, and age group definitions 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 (Ref). In patients with impending cardiac arrest, some experts administer a 50 mg bolus over 2 minutes, followed by a 50 mg infusion over the next 2 hours (Ref). 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

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

IV, intra-arterial, intraosseous, intrapleural:

Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction (rapid plasma clearance mediated by the liver (Ref).

Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzed (large molecular weight): No supplemental dose or dosage adjustment necessary (Ref).

Peritoneal dialysis: Unlikely to be dialyzed (large molecular weight): No dosage adjustment necessary (Ref).

CRRT: No dosage adjustment necessary (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (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

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (thrombolytic agent) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care Settings).

Other safety concerns:

TPA, tPA are error-prone abbreviations (mistaken as TNK [TNKase, tenecteplase], TXA [tranexamic acid], another tissue plasmogen activator Retavase [retaplase])

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 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: Alteplase may enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination

Aprotinin: May diminish the therapeutic effect of Thrombolytic Agents. 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

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 | Cathflo;
  • (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
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