Parenteral Manual

Alteplase

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Alternate Name(s): 
Activase rt-PA, Tissue plasminogen activator (TPA), Cath-Flo
Classification: 
Thrombolytic/Fibrinolytic Agent
Original Date: 
August 2005
Revised Date: 
March 2023
Indications: 
  • Lysis of suspected occlusive coronary artery thrombi associated with evolving myocardial infarct (MI)
  • Management of complete occlusion of blocked central venous access devices
  • Management of an occluded drain (percutaneous or transrectal drain)
  • Treatment of acute ischemic stroke
Reconstitution and Stability: 

VIAL SIZE  

STERILE WATER for INJECTION REQUIRED

FINAL CONCENTRATION 

50 mg (with vacuum)

50 mL provided

1 mg/mL

2 mg (in fridge)

2.2 mL

1 mg/mL
  • Slight foaming may occur; allow vial to stand undisturbed for several minutes until large bubbles disappear.  Swirl gently to dissolve. DO NOT SHAKE.
  • Reconstituted solutions are stable for 8 hours at room temperature or refrigerated
  • Reconstituted solution resutls in colourless to pale yellow transparent solution
Compatibility: 
  • Solutions Compatible: 0.9% NaCl, D5W
  • Additives/Above Cassette Compatible: morphine
  • Y-site Compatible: lidocaine HCl, metoprolol, propanolol

Incompatible: dobutamine, dopamine, heparin, ringer's lactate, preservative-containing solutions  (e.g., bacteriostatic water for injection)

 

Administration: 

(For approved routes of administration by nursing personnel, refer to Policy for the Administration of Intravenous Medications.)

SC NO
IM NO
IV Direct YES
Infusion time: 2 minutes
IV Intermittent Infusion NO
IV Continuous Infusion

YES
Usual dilution: 1 mg/mL
  • Can be given via drain or intra central venous access and left for instillation (may be administered by RN)
  • Can be given into the pleural space via chest tube and left for instillation (physician only)
Dosage: 

(For neonatal dosages, refer to Neonatal IV Drug Manual.)

Pediatrics:

NOTE:  DO NOT administer to patient awaiting cardiovascular surgery (up to 1 week prior to surgery) and up to two months post operatively without contacting the cardiovascular service

  • Acute ischemic stroke:
    • >2 to <12 years: 0.75 mg/kg/dose (Max dose 75 mg)
      • 0.075 mg/kg (10% of dose) as an IV bolus over 5 minutes, followed by  0.675 mg/kg (90% of dose) as a continuous infusion over 1 hour
    • > 12 years: 0.9 mg/kg/dose (Max dose 90 mg)
      • 0.09 mg/kg (10% of dose) as an IV bolus over 5 minutes, followed by 0.81 mg/kg (90% of dose) as a continuous infusion over 1 hour
  • Systemic Thrombosis:
    •  Initial: 0.1 mg/kg/hr IV for 6 hours- monitor closely for bleeding and fibrinogen levels
    •  If no response after 6 hours, increase by 0.1 mg/kg/hr at 6 hour intervals to maximum of 0.5  mg/kg/hr
    •  Duration of therapy based on clinical response
  • Management of blocked central venous access devices: 
    • 0.2 - 2 mL (depending on caliber and length of catheter) and leave in place for 1-2 hours before attempting to aspirate.
      • For tunneled, non-tunneled and PIC catheters:  1 mL instilled as above
      • Dialysis catheters:  Instill alteplase equivalent to lumen volume + 0.2 mL as above
      • Totally implanted devices: 2 mL instilled as above
  • Pleural Effusion via chest tube: 
    • Infants less than 2 years:  2 mg (2 mL) added to 4 mL 0.9% NaCl daily x 3 days. Flush tube with 10 - 20 mL 0.9% NaCl immediately following alteplase
    • Children 2 years and older:  4 mg (4 mL) added to 8 mL 0.9% NaCl daily x 3 days.  Flush tube with 20 - 40 mL 0.9% NaCl immediately following alteplase
  • Occluded percutaneous or transrectal drain:
    • Infants less than 2 years: 2mg (2ml) added to 8ml 0.9% NS (total 10ml) once.  Flush tube with 10ml 0.9% NS immediately following Alteplase and clamp drain for prescribed time.
    • Children 2 years and older: 4mg (4ml) added to 6ml 0.9% NS (total 10ml) once.  Flush tube with 10ml 0.9% NS immediately following Alteplase and clamp drain for prescribed time.                                        
Potential hazards of parenteral administration: 
  • Bleeding complications, re-perfusion arrhythmias, re-infarction
    • Intracranial hemorrhage
    • Cerebrovascular hemorrhage
    • Eccymosis
  • Extravasation can cause ecchymosis (small hemorrhagic spot) and/or inflammation: terminate infusion at the site and apply local therapy
Notes: 
  • Contraindications for use in acute ischemic stroke:
    • < 2 years of age
    • Stroke symptom onset >6 hours ago
    • Evidence of hemorrhage on pre-treatment neuroimaging
    •  Stroke or serious head trauma in previous 3 months
    • Intracranial or intraspinal surgery in previous 3 months
    • Intracranial neoplasm, arteriovenous malformation, aneurysm, or history of intracranial hemorrhage
    • Known bleeding diathesis including (but not limited to):
      • Anticoagulation (LMWH, warfarin, unfractionated heparin) in last 24 hours
      • Dual antiplatelet therapy: ASA (in last 5 days) + clopidogrel (in last 7 days)
        • May proceed with administration in patients receiving ASA/clopidogrel as a single agent or NSAIDs
      • DOAC (rivaroxaban, edoxaban, apixaban, betrixaban, dabigatran) in last 48 hours
      • Other anticoagulants (bivalrudin, argatroban, fondaparinux) require STAT multidisciplinary discussion to determine eligibility 
      • PTT > 40 seconds
      • INR > 1.4
      • Fibrinogen < 1.0
      • Platelets < 100 x 109/L
      • Significant bleeding disorder
      • Glucose < 4 or > 22 mmol/L
      • Pregnant or lactating female
      • Major surgery or parenchymal biopsy within the previous 14 days
      • Active internal bleeding or GI/GU bleeding within the last 21 days
      • Uncontrolled hypertension (>33% above for normal for age) at time of tPA administration or aggressive treatment required to reduce BP to specified limits
  • Local Instillation:
    • See Infusion Therapy Manual, Section I, for step-by-step management of blocked central venous devices
    • DO NOT force an obstruction since it could cause emboli to enter venous system
  • For occluded percutaneous or transrectal drain:
    • Monitor for pain and bleeding at drain site
  • Monitor blood pressure, CBC, reticulocyte, platelet count, fibrinogen level, plasminogen, fibrin/fibrinogen degradation products, D-dimer, PT, PTT, antithrombin III, protein C, urinalysis, signs of bleeding
  • Pleural Instillation:
      Patient is to be placed on cardio/respiratory monitor for procedure
      -  Pre-instillation:  monitor baseline vital signs - temperature, heart rate, respiratory rate and blood pressure
      -  Post instillation:  monitor vital signs and chest tube system Q20 minutes x 2 , then Q1H x 2

     Notify the physician if the patient experiences any of the following symptoms:
     -  Difficulty breathing during/after irrigation/instillation
     -  Signs and symptoms of bleeding
     -  Significant pain during/after irrigation/instillation
     -  Chest tube drainage greater than 3 mL/kg/hour over 3 continuous hours or greater than 5 mL/kg/hour over 1 hour

References: 
  1. Rivkin MJ, deVeber G, Ichord RN, et al. Thrombolysis in pediatric stroke study. Stroke. 2015;46(3):880-885. doi:10.1161/STROKEAHA.114.008210
  2. Activase rt-PA Product Monograph (Roche Canada)
  3. Alteplase monograph (Lexicomp)

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