Genentech has issued a communication to inform health care providers of a temporary supply shortage of Activase (alteplase) 100 mg kits and to provide instructions for preparing Activase doses exceeding 50 mg. Currently the co-packed transfer device in the Activase 100 mg kit is unavailable. Until availability is restored, Genentech recommends using two Activase 50 mg vials for doses exceeding 50 mg. Full instructions for preparation using Activase 50 mg vials are available at https://www.gene.com/download/pdf/activase_instructions_for_alternate_preparation.pdf.
Health care providers may need to assess, identify, and modify internal processes to ensure appropriate storage, preparation, and administration of alteplase doses exceeding 50 mg using two Activase 50 mg vials.
Additional information is available at https://www.gene.com/download/pdf/Activase_DHCP_Letter_October2021.pdf.
Occluded IV catheter: 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: Central venous catheter: 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; leave in lumen for up to 2 hours, then aspirate out of catheter; may instill a second dose if catheter remains occluded after 2-hour dwell time
Alternate dosing:
Chest guidelines (Monagle 2008): Limited data available: Central venous catheter: 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; flush catheter with NS. Note: The most recent guidelines (2012) continue to recommend alteplase as a treatment option but specific dosage recommendation is not provided (Monagle 2012).
Soylu, 2010: Limited data available: Central venous catheter: 0.25 to 0.5 mg/mL solution; instill a volume to fill the catheter; leave in lumen for up to 2 hours, then aspirate out of catheter; dosing described in trial of 18 neonates including four patients with GA ≤32 weeks
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 thrombosis if the catheter is already in place (Monagle 2012). Various "low-dose" regimens have been used, both with local (or regional) and systemic administration.
Standard dose infusion: IV: Note: The optimal dose for various thrombotic conditions is not established; most published papers consist of case reports and series; few prospective neonatal studies have been conducted; dose must be titrated to effect (eg, fibrinogen >100 to 150 mg/dL). Administration of FFP may be considered prior to dose infusion. Current Chest guidelines recommend use only when major vessel occlusion is causing critical compromise of organs or limbs in the neonate (Monagle, 2012).
Chest guidelines (Monagle 2012): Limited data available: Usual dose: 0.5 mg/kg/hour for 6 hours; reported 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 (Monagle 2008; Monagle 2012).
Additional reported standard dose regimens:
No loading dose regimens: Very limited data available: Seven neonates (GA: 24 to 38 weeks) with arterial thrombosis received a continuous IV infusion of 0.1 mg/kg/hour initially; infusion rate was titrated to maintain fibrinogen levels >100 mg/dL; dosage increases were made in 0.1 mg/kg/hour increments every 6 hours to a maximum of 0.4 mg/kg/hour; no heparin was used in these patients (Weiner, 1998). In case series of three neonates (GA: 26 to 36 weeks) with infective endocarditis and intracardiac thrombosis, a daily intermittent infusion of 0.2 mg/kg/hour over 6 hours for 5 days was used (Anderson, 2009).
Loading dose regimens: Limited data available; dosage reported varies widely: One trial of 16 neonates used a loading dose of 0.1 mg/kg over 10 minutes, followed by an intermittent infusion of 0.3 mg/kg/hour infusion for 3 hours every 12 to 24 hours as determined by response and monitoring parameters; a maximum of 4 additional intermittent doses were allowed; heparin was held during alteplase infusion (Farnoux, 1998). In another trial, a loading dose of 0.7 mg/kg bolus over 30 to 60 minutes was used followed by continuous IV infusion at an initial rate of 0.2 mg/kg/hour for 1 to 4 days in 13 neonates (GA: 27 to 42 weeks) with catheter-related thrombosis (used in conjunction with heparin infusion); reported effective range: 0.1 to 0.3 mg/kg/hour (Hartmann 2001).
Low dose infusion: Very limited data available: Initial dose: IV: 0.02 to 0.03 mg/kg/hour, titrate dose based on patient response, range reported 0.01 to 0.06 mg/kg/hour; duration of therapy based on patient response. A trial comparing standard-dose and low-dose alteplase in pediatric patients included five neonates (four preterm; PNA 1 to 14 days) with acute thrombus in low-dose group; dosing in neonates was initiated at 0.03 mg/kg/hour, in three neonates receiving systemic therapy, the effective dose was 0.03 mg/kg/hour in one patient and 0.06 mg/kg/hour in the other two patients; the remaining two neonates received local infusions and required a higher infusion rate (0.1 mg/kg/hour and 0.24 mg/kg/hour); duration of therapy ranged from 48 to 70 hours; complete clot resolution occurred in all patients. One preterm neonate with staphylococcal sepsis experienced a subdural bleed at the dose of 0.24 mg/kg/hour (Wang, 2003). One case series of four neonates and infants (PNA: 25 to 43 days, 2 preterm) with caval thrombosis due to central line reported using 0.02 to 0.1 mg/kg/hour with mixed results; resolution of clot occurred in only two patients (Anderson 1991).
Occluded IV catheters: 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 (Monagle 2008): Note: The most recent guidelines (2012) continue to recommend alteplase as a treatment option but specific dosage recommendation is not provided (Monagle 2012)
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: 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 (Monagle 2012).
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 (Levy 1991; Weiner 1998): 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 (Giglia 2013; Monagle 2008; Monagle 2012).
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 (Giglia 2013)
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 (Doyle 1992).
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 (Giglia 2013)
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) (Bradley 2011; St. Peter 2009)
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) (Bradley 2011; Hawkins 2004)
There are no dosage adjustments provided in manufacturer's labeling.
There are no dosage adjustments provided in manufacturer's labeling.
(For additional information see "Alteplase: Drug information")
Acute ischemic stroke: Note: Perform non-contrast-enhanced CT or MRI prior to administration. After ensuring all eligibility criteria are met, administer within 3 hours (labeled use) or 3 to 4.5 hours (off-label use) of symptom onset (AHA/ASA [Powers 2019]; Hacke 2008). 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) (Thomalla 2018; Tsivgoulis 2020). 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 (AHA/ASA [Powers 2019]; Filho 2021).
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 clearance:
Central venous catheter clearance:
Intra-catheter:
Patient weight ≥30 kg: 1 or 2 mg; retain in catheter for 30 minutes to 2 hours; may instill a second dose if catheter remains occluded after 2 hours (Fink 2004; Whigham 2002; manufacturer's labeling).
Hemodialysis catheter 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; retain 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 (BCPRA 2017; KDOQI [Lok 2020]).
Long dwell (post-hemodialysis): Instill 1 to 2 mg per lumen, then instill saline to fill the internal volume; retain in hemodialysis catheter until next hemodialysis session (BCPRA 2017).
Peritoneal dialysis catheter 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 6 mg; retain in peritoneal catheter for 1 to 2 hours or until next peritoneal dialysis session; attempt to drain using a twin bag or larger syringe and withdraw volume of alteplase solution instilled; then perform a full in-and-out flush of dialysate to remove any residual alteplase in catheter; may repeat if catheter remains occluded (BCPRA 2018; Golper 2020).
Frostbite (off-label use): Note: May consider in patients who present within 24 hours of deep frostbite injury and are at high risk for life-altering amputation. Prior to use, evaluate alteplase contraindications. Parenteral anticoagulation is administered in conjunction with thrombolytic therapy and continued for 14 days (Hickey 2020; Nygaard 2017; WMS [McIntosh 2019]). 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 (Nygaard 2017; Zafren 2020).
Examples of 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) (Hickey 2020; Johnson 2011; Nygaard 2017).
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 (Bruen 2007; Gonzaga 2016; Ibrahim 2015; Paine 2020).
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 (Pislaru 2020a; Pislaru 2020b). 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 (Özkan 2015; Pislaru 2020a; Pislaru 2020b).
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) (ACC/AHA [Otto 2021]; Pislaru 2020a; Pislaru 2020b).
Parapneumonic effusions, complicated and empyema (off-label use): Note: Consider thrombolytic use in patients who do not sufficiently respond to conventional therapy (eg, chest tube drainage and antibiotics) and/or who are not surgical candidates (Piccolo 2014). Optimal regimen and doses have not been identified; refer to institutional protocols.
Intrapleural: 10 mg twice daily for 3 days; must be used sequentially or concurrently with intrapleural dornase alfa. For sequential dosing, let alteplase dwell for ~1 hour and drain for ~1 hour, then administer dornase alfa using the same dwell and drain sequence (Piccolo 2014; Rahman 2011). For concurrent dosing, administer alteplase and dornase alfa via 2 separate syringes, followed by a 60 mL saline flush, then dwell for ~2 hours (Majid 2016).
Peripheral arterial occlusion, acute (off-label use): Note: Consider thrombolytic use as an alternative to surgery at centers experienced with interventional radiology (ACCP [Alonso-Coello 2012]). 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 (Disini 2008; Grip 2014; Meyerovitz 1990; Schweizer 1996; Semba 2000). 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 (McFarland 2022).
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 (McFarland 2022).
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. Systemic thrombolysis followed by anticoagulation may be considered for patients with severe right ventricular dysfunction and elevated troponin and/or brain natriuretic peptide levels (ASH [Ortel 2020]; ESC [Konstantinides 2020]). Some experts prefer catheter-directed therapy (CDT) if the expertise is available and the patient has a low risk of bleeding; or may consider CDT over systemic thrombolysis in patients with an increased risk of bleeding or with contraindications to systemic thrombolytic therapy (Tapson 2021).
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 (ASH [Ortel 2020]; Tapson 2021). 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 (Kucher 2014; Kuo 2015; Piazza 2015; Tapson 2018).
Pulmonary embolism: Acute (hemodynamically unstable, high risk [massive]): Note: Consider systemic thrombolytic therapy followed by anticoagulation over anticoagulation alone (ASH [Ortel 2020]; ESC [Konstantinides 2020]). Systemic thrombolysis is generally preferred over CDT since systemic treatment can be completed more rapidly (ASH [Ortel 2020]; Tapson 2021). Some experts prefer CDT, when expertise (eg interventional radiology) is available, if systemic thrombolysis is contraindicated or in patients with an increased bleeding risk or persistent hemodynamic instability despite systemic thrombolysis (Tapson 2021).
IV: 100 mg infused over 2 hours.
Patients with impending cardiac arrest: 20 mg bolus, followed by 80 mg infused over the next 2 hours (Tapson 2021).
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 (Tapson 2021).
Catheter-directed thrombolysis: (off-label use): Note: For use at experienced centers; may be performed with ultrasound and catheter-assisted thrombus removal (ASH [Ortel 2020]; Tapson 2021). 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 (Kucher 2014; Kuo 2015; Piazza 2015; Tapson 2018).
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) (AHA [Panchal 2020]).
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. Use therapeutic IV anticoagulation in addition to thrombolytic therapy (AHA [Lavonas 2015]; Böttiger 2001; ESC [Konstantinides 2020]). Note: When administered via intraosseous catheter, monitor for extravasation and subcutaneous bleeding at the intraosseous catheter insertion site (Landy 2012; Logan 2014).
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 (ACCF/AHA [O'Gara 2013]; ESC [Ibanez 2018]).
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.
There are no dosage adjustments provided in the manufacturer’s labeling. Plasma clearance is rapid and mediated primarily by the liver; therefore, degree of renal impairment is unlikely to influence elimination of alteplase. Hemostatic defects due to severe renal disease may increase the risk for bleeding.
Hemodialysis: Dialyzable: Unknown, but unlikely (NCS/SCCM [Frontera 2016])
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.
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]
No
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)
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 (Hawkins 2004) or 1 hour (Rahman 2011; St. Peter 2009) dwell time; after dwell period, release clamp and connect chest tube to continuous suction.
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 (ACCP [Kearon 2012]; ACCP [Kearon 2016]).
PE with cardiac arrest (off-label use): During cardiopulmonary resuscitation, administer as a rapid IV bolus over 2 minutes (AHA [Lavonas 2015]; Böttiger 2001). 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 (Landy 2012; Logan 2014).
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 (BCPRA 2017).
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 (BCPRA 2018).
Intrapleural: Parapneumonic pleural effusions and empyemas (off-label use): Adults: For sequential administration of alteplase and dornase alfa, dilute each dose in 30 mL sterile water. Instill dose into chest tube and clamp drain. Although the optimum dwell time has not been determined, clinical trials more often have used either a 45-minute (Hawkins 2004) or 1-hour (Rahman 2011; St. Peter 2009) dwell time; after dwell period, release clamp and connect chest tube to continuous suction. For concurrent administration of alteplase and dornase alfa, using separate syringes, dilute each dose in 50 mL of normal saline. Instill each dose into chest tube, one immediately after the other, followed by a 60 mL normal saline flush. Clamp drain; after 2-hour dwell time, release clamp (Majid 2016).
IV infusion: 0.5 mg/mL or 1 mg/mL
Activase: Store intact vials at room temperature (not to exceed 30°C [86°F]), or under refrigeration at 2°C to 8°C (36°F to 46°F); protect from light. Store reconstituted solution at 2°C to 30°C (36°F to 86°F) and use within 8 hours. Discard any unused solution
Cathflo Activase: Store intact vials at 2°C to 8°C (36°F to 46°F); protect from light. Store reconstituted solution at 2°C to 30°C (36°F to 86°F) and use within 8 hours. Discard any unused solution.
Solutions of 0.5 mg/mL, 1 mg/mL, and 2 mg/mL in SWI retained ≥94% of fibrinolytic activity at 48 hours when stored at 2°C in plastic syringes; these solutions retained ≥90% of fibrinolytic activity when stored in plastic syringes at -25°C or -70°C for 7 or 14 days, thawed at room temperature and then stored at 2°C for 48 hours (Davis 2000). Solutions of 1 mg/mL in SWI were stable for 22 weeks in plastic syringes when stored at -30°C and for ∼1 month in glass vials when stored at -20°C; bioactivity remained unchanged for 6 months in propylene containers when stored at -20°C and for 2 weeks in glass vials when stored at -70°C (Generali 2001).
Activase: Thrombolytic agent used in treatment of acute MI, acute ischemic stroke, and acute massive pulmonary embolism (All indications: FDA approved in adults)
CathFlo Activase: Treatment of occluded central venous access devices (catheters) to restore function (FDA approved in pediatric patients [age not specified] and adults)
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)
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.
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
Hypersensitivity to alteplase or any component of the formulation.
Indication-specific contraindications | |
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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]). |
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.
• 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:
• Elderly: 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.
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.
None known.
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 Lexicomp or 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
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
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
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
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 may be increased by pregnancy.
Case reports describe the use of alteplase in pregnant women 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 women. 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. Information related to early postpartum use is limited (Akazawa 2017).
Systemic use: Blood pressure; CBC, reticulocyte, platelet count; fibrinogen level, plasminogen, fibrin/fibrinogen degradation products, PT, PTT, signs of bleeding
Intracatheter use: Catheter function (by attempting to aspirate blood); signs of sepsis, GI bleeding, bleeding at injection site, and venous thrombosis
Initiates local fibrinolysis by binding to fibrin in a thrombus (clot) and converts entrapped plasminogen to plasmin
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)
Activase and CathFlo Activase also contain L-arginine and phosphoric acid (for pH adjustment). Advantages of alteplase include: Low immunogenicity, short half-life, direct activation of plasminogen, and a strong and specific affinity for fibrin.
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): $183.67
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