| Acute MI: (>67kg): 15 mg IV bolus over 1-2 minutes, then 50 mg over 30 minutes, then 35 mg over next 60 minutes. (<67kg): 15 mg IV bolus, followed by 0.75 mg/kg (maximum 50mg) over 30 minutes, then 0.5 mg/kg (maximum 35mg) over the next 60 minutes. Note: Concurrently, begin heparin 60 units/kg bolus (maximum: 4000 units) followed by continuous infusion of 12 units/kg/hour (maximum: 1000 units/hour) and adjust to aPTT target of 1.5-2 times the upper limit of control. Infuse remaining 35 mg of alteplase over the next hour.
Acute PE: 100mg IV over 2 hours, then restart heparin when PTT < twice normal.
Acute ischemic stroke: Doses should be given within the first 3 hours of the onset of symptoms. Recommended total dose: 0.9 mg/kg (maximum dose should not exceed 90 mg) infused over 60 minutes. Load with 0.09 mg/kg (10% of the 0.9 mg/kg dose) as an IV bolus over 1 minute, followed by 0.81 mg/kg (90% of the 0.9 mg/kg dose) as a continuous infusion over 60 minutes. Heparin should not be started for 24 hours or more after starting alteplase for stroke.
Central venous catheter clearance: Intracatheter (Cathflo™ Activase® 1 mg/ml): Patients <30 kg: 110% of the internal lumen volume of the catheter, not to exceed 2 mg/2 ml. Retain in catheter for 0.5-2 hours. May instill a second dose if catheter remains occluded. Patients >30 kg: 2 mg/2ml- retain in catheter for 0.5-2 hours – may instill a second dose if catheter remains occluded.
Acute peripheral arterial occlusive disease (unlabeled use): Intra-arterial: 0.02-0.1 mg/kg/hour for up to 36 hours. The most common indications for thrombolysis were peripheral arterial occlusion and venous thrombosis. Preparation: Continuous infusion of alteplase (50 mg of alteplase reconstituted in 50 mL of sterile water and diluted with 0.9% normal saline solution to a concentration of 0.1 to 0.2 mg/mL). Infusion rate: 0.5 to 2 mg/hr x 6 to 72 hours depending on location.
Supplied: 50 mg, 100 mg vial ( powder for reconstitution). Cathflo: 2 mg.
Vancouver General Hospital Protocols
RECONSTITUTION AND STABILITY : 50mg and 100mg powder stable at room temperature; 2mg powder stable in fridge. reconstitute each 2mg, 50mg or 100mg vial with 2.2mL, 50mL or 100mL sterile water for injection, respectively (diluent provided with 50mg and 100mg vials). DO NOT USE bacteriostatic water. To avoid foaming, direct the stream of water down the side of the vial. DO NOT SHAKE. Roll the vial in the palm of hands to mix. The reconstituted solution yields a final concentration of 1mg/mL. following reconstitution, unused solution may be stored in freezer (-20°C) for 6 months, at room temperature for up to 8 hours or under refrigeration for 24 hours. Minimum dilution in D5W 0.5mg/mL; dilution in NS may be < 0.5mg/mL; diluted solutions to these concentrations stable x 24 hours at room temperature.
ROUTES OF ADMINISTRATION
2) Acute Ischemic Stroke: 0.9mg/kg to a maximum dose of 90mg given as follows: 10% of total dose given as a bolus over 2 minutes immediately followed by 90% of total dose given IV by continuous infusion over 60 minutes
3) Massive Pulmonary Embolism: 100 mg IV infusion over 2 hours; initiate heparin at end of alteplase infusion.
4) Lysis of Central Venous Catheter Occlusion: for lumen volumes < 1mL , instil 1mL (1mg) of 1mg/mL solution; for lumen volumes > 1mL, instil 2mL (2mg) of 1mg/mL solution. Dwell x 1 hour, then aspirate; may repeat x 1. For hemodialyis patients: instil 1mL of 1mg/1mL solution into lumen of catheter, then add NS to catheter volume + 0.2mL (e.g. if lumen volume is 2.2mL, instil 1mL altpelase and follow with 1.4mL NS); dwell x 1 hour then aspirate or leave in situ until next dialysis. CVC Partial Occlusion – 2 mg/50mL NS infused over 2 hours; monitor vital signs q1h during infusion. Note this dose of alteplase does not cause systemic thrombolysis
5) Infusion for Lysis of Acute Occlusion: 0.5 – 2.0mg/hour (usual 1mg/hour) intracannular x 6-72 hours.
6) Pleural Instillation: 4-6 mg (up to 0.1 mg/kg) in 30-100 mL NS instilled via chest tube; dwell 1-2 hours; may repeat daily until resolution of pleural fluid drainage (1-14 days)
| CLINICAL PHARMACOLOGY
General: Retavase® is a recombinant plasminogen activator which catalyzes the cleavage of endogenous plasminogen to generate plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action.1,2 In a controlled trial, 36 of 56 patients treated for an acute myocardial infarction (AMI) had a decrease in fibrinogen levels to below 100 mg/dL by 2 hours following the administration of Retavase® as a double-bolus intravenous injection (10 + 10 unit) in which 10 units (17.4 mg) was followed 30 minutes later by a second bolus of 10 units (17.4 mg).3 The mean fibrinogen level returned to the baseline value by 48 hours.
INDICATIONS AND USAGE
| Adults: Antibodies to streptokinase remain for at least 3-6 months after initial dose: Administration requires the use of an infusion pump. An intradermal skin test of 100 units has been suggested to predict allergic response to streptokinase. If a positive reaction is not seen after 15-20 minutes, a therapeutic dose may be administered.
Acute MI: 1.5 million units IV over 60 minutes. ( Administer as soon as possible after onset of symptoms. The greatest benefit in mortality reduction was observed when Streptokinase was administered within four hours, but statistically significant benefit has been reported up to 24 hours). Administration: Dilute two 750,000 unit vials of streptokinase with 5 mL dextrose 5% in water (D5W) each, gently swirl to dissolve. Add this dose of the 1.5 million units to 150 mL D5W. This should be infused over 60 minutes; an in-line filter 0.45 micron should be used. Monitor for the first few hours for signs of anaphylaxis or allergic reaction. Infusion should be slowed if blood pressure falls by 25 mm Hg or terminated if asthmatic symptoms appear. Following completion of streptokinase, initiate heparin, if directed, when aPTT returns to less than 2 times the upper limit of control; do not use a bolus, but initiate infusion adjusted to a target aPTT of 1.5-2 times the upper limit of control. If prolonged (>48 hours) heparin is required, infusion may be switched to subcutaneous therapy.
Acute pulmonary embolism (APE): 3 million unit dose over 24 hours. Administration: Dilute four 750,000 unit vials of streptokinase with 5 mL dextrose 5% in water (D5W) each, gently swirl to dissolve. Add this dose of 3 million units to 250 mL D5W, an in-line filter 0.45 micron should be used. Administer 250,000 units (23 mL) over 30 minutes followed by 100,000 units/hour (9 mL/hour) for 24 hours. Monitor for the first few hours for signs of anaphylaxis or allergic reaction. Infusion should be slowed if blood pressure is lowered by 25 mm Hg or if asthmatic symptoms appear. Begin heparin 1000 units/hour about 3-4 hours after completion of streptokinase infusion or when PTT is <100 seconds. Monitor PT, PTT, and fibrinogen levels during therapy.
Important note: Since human exposure to streptococci is common, antibodies to Streptokinase are prevalent. Thus, a loading dose of Streptokinase sufficient to neutralize these antibodies is required. A dose of 250,000 IU of Streptokinase infused into a peripheral vein over 30 minutes has been found appropriate in over 90% of patients. Furthermore, if the thrombin time or any other parameter of lysis after 4 hours of therapy is not significantly different from the normal control level, discontinue Streptokinase because excessive resistance is present.
Thromboses: 250,000 units to start, then 100,000 units/hour for 24-72 hours depending on location.
Cannula occlusion: 250,000 units into cannula, clamp for 2 hours, then aspirate contents and flush with normal saline; Not recommended.
| CLINICAL PHARMACOLOGY
Tenecteplase is a modified form of human tissue plasminogen activator (tPA) that binds to fibrin and converts plasminogen to plasmin. In the presence of fibrin, in vitro studies demonstrate that Tenecteplase conversion of plasminogen to plasmin is increased relative to its conversion in the absence of fibrin. This fibrin specificity decreases systemic activation of plasminogen and the resulting degradation of circulating fibrinogen as compared to a molecule lacking this property. Following administration of 30, 40, or 50 mg of TNKase, there are decreases in circulating fibrinogen (4%–15%) and plasminogen (11%–24%). The clinical significance of fibrin-specificity on safety (e.g., bleeding) or efficacy has not been established. Biological potency is determined by anin vitro clot lysis assay and is expressed in Tenecteplase-specific units. The specific activity of Tenecteplase has been defined as 200 units/mg.
INDICATIONS AND USAGE
Treatment should be initiated as soon as possible after the onset of AMI symptoms. The recommended total dose should not exceed 50 mg and is based upon patient weight. A single bolus dose should be administered over 5 seconds based on patient weight.
Preparation: dilute 50mg vial with 10ml sterile water (packaged with diluent and syringe).
All patients received 150-325 mg of aspirin as soon as possible and then daily. Intravenous heparin was initiated as soon as possible and aPTT was maintained between 50-70 seconds. Do not shake when reconstituting. Slight foaming is normal and will dissipate if left standing for several minutes. The reconstituted solution is 5 mg/mL. Any unused solution should be discarded. Tenecteplase is incompatible with dextrose solutions. Dextrose-containing lines must be flushed with a saline solution before and after administration. Administer as a single I.V. bolus over 5 seconds.
Supplied: 50 mg vial ( powder for reconstitution).
National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
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