NAME OF DRUG
alteplase

CLASSIFICATION

Fibrinolytic Agent

ALTERNATE NAME

ACTIVASE, tissue-type plasminogen activator, rt-PA

INDICATIONS

1)    lysis of coronary artery thrombosis associated with myocardial infarction in the following patients:

• all anterior myocardial infarctions
• inferior myocardial infarctions with right ventricular involvement
• persons requiring repeat thrombolysis
• onset of chest pain to therapy should be less than 12 hours

2) Thrombolysis in acute ischemic stroke

• onset of ischemic stroke to therapy should be within 3 hours

3) Thrombolysis in Acute Massive Pulmonary Embolism

5) Lysis of acute occlusion of an artery, vein, catheter, or graft including: dialysis fistula or PFTE graft, axillary vein thrombosis, lower extremity DVT, acute peripheral arterial embolus or thrombosis, peritoneal-arterial shunt (Denver).

6) Pleural effusion

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

COMPATIBILITY

• compatible with NS and D5W
• compatible with lidocaine, metoprolol and propranolol when administered by Y-site injection
• incompatible with most drugs

ROUTES OF ADMINISTRATION

• intracannular dwell - 1mg/1mL concentration

• intracannular infusion 

  • Radiology: dilute 12 mg in 500 mL NS (=1mg/42mL)

  • Hemodialysis Unit: dilute 2-4 mg in 50 mL NS; infuse over 1-2 hours

• IV bolus - loading dose ONLY

• IV infusion with an infusion pump - do not use in-line filter

• intracoronary - restricted to interventional cardiology
•  intrapleural – dilute  dose in 30-100 mL NS - restricted to physician only

VH & HSC ADMINISTRATION POLICY

Restricted to ICU, CCUA, Emergency Acute, Neuroradiology, Radiology and Cardiac Catheter Lab for intravenous use.  Vascular surgery patients on general nursing units may be administered IV infusions only if initiated in the above listed areas.
Intracannular dwell may be given on any nursing unit.
Hemodialysis Unit may administer intracannular infusion for CVC occlusion

B - Direct IV reoute restricted to critical care nurses in above listed areas.

H - The IV infusion rate MUST be controlled by an automated infusion device.

DOSAGE

1) Myocardial infarction:

Total recommended dose should not exceed 100 mg IV administered as follows: 

• 15 mg as a bolus dose over 2 minutes

• immediately followed by 0.75 mg/kg (not exceeding 50 mg) as a continuous infusion over the first 30 minutes

• then 0.50 mg/kg IV (not exceeding 35 mg) over the next 60 minutes.

For Intracoronary Use:

• first 25 mg administered into coronary artery at rate of 1 mg/min; next 25 mg administered intravenously at rate of 5 mg/hr (i.e. over 5 hours)  

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:

  • Dwell: 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.

  • Infusion: 2 or 4 mg/100mL NS infused via Y-connector over 1-2 hours; monitor vital signs q1h during infusion
    

• see Patient Care Guidelines Manual (Policies # C260, C270, C280, C290, I220)

• 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)

POTENTIAL HAZARDS OF PARENTERAL ADMINISTRATION

• hemorrhage - severe bleeding may occur
• hypotension
• reperfusion arrhythmias

IMPORTANT IMPLICATIONS

• Contraindications:

a) acute myocardial infarction or infusion for lysis of acute occlusion: active internal bleeding; active peptic ulcer disease; recent (within  2 months) stroke, intracranial or intraspinal surgery; intracranial neoplasm; severe uncontrolled hypertension (i.e. diastolic BP> 110mmHg and/or systolic BP> 180mmHg); recent prolonged cardiopulmonary resuscitation; recent (within 10 days) severe trauma

b) acute ischemic stroke: intracranial hemorrhage (current via CT or history), intracranial neoplasm or vascular malformation (except meningioma), blood pressure > 185/110, anticoagulant use within previous 48 hours and a prolonged PTT or INR > 1.7 or platelet count < 100,000, stroke, intracranial surgery or head injury within 3 months, major surgery within 14 days, blood glucose < 3 or > 22mmol/L, seizures at onset of stroke, other internal bleeding within 21 days, myocardial infarct within 3 weeks, aortic dissection or percarditis, arterial puncture at a non-compressible site within 7 days, recent lumbar puncture, subarachnoid hemorrhage, rapidly improving neurological signs or minimal deficit, pregnancy

• avoid IM injections

• venipuncture should be performed carefully; upper extremity vessels are preferable.

• For acute ischemic stroke management:

a)  monitor vital signs q15 min x 2 hours, then q30min x 6 hours, then q1h until 24 hours post treatment
b)  monitor neurovital signs q1h x 6 hours then to be reassessed

Rev. Apr 2008