alteplase (Activase)

Introduction

Tradename: Activase.

Indications

• arterial thrombosis
  • post myocardial infarction clot lysis
    • within 4-6 hours of symptom onset
    • ongoing symptoms
  • unstable angina
    • benefit over streptokinase in middle aged men with anterior myocardial infarction
  • acute ischemic stroke: within 4.5 hours of onset
    • recent use of direct-acting oral anticoagulants not associated with increased risk or intracranial hemorrhage among patients with acute ischemic stroke treated with alteplase
  • occluded AV cannula
• venous thrombosis
  • deep vein thrombosis & venous thromboembolism
    • life-threatening pulmonary embolism
  • central venous catheter occlusion
• hemolytic uremic syndrome

Contraindications

• absolute contraindications
  • previous hemorrhagic stroke within 1 year
  • known intracranial neoplasm
  • active internal bleed
  • suspected aortic dissection
• relative contraindications
  • blood pressure > 180/110
  • current anticoagulation therapy (warfarin)
  • recent trauma (surgery, head, CPR)
  • active peptic ulcer disease
• NO IM injections
• prior ischemic stroke & diabetes appear not to be contraindications
• some patients on warfarin (INR < 1.8) may safely receive r-tPA following ischemic stroke

tPA is apparently safe if used in patients with stroke mimetic

Pregnancy category: C

Safety in lactation: ?

Dosage

• GUSTO accelerated dose for acute MI:
  • 15 mg IV bolus (no bolus), then
  • 0.75 mg/kg (max 50 mg) over 30 min, then
  • 0.5 mg/kg (max 35 mg) over next 60 min*
  • up to 100 mg over 90 min
  • concurrent heparin infusion*
• arterial thrombus
  • 100 mg IV over 2 hours, followed by
  • IV heparin when aPTT returns to < 2x normal*
• acute ischemic stroke:
  • FIRST rule out hemorrhage
  • 0.9 mg/kg IV (max 90 mg)
    • bolus with 10% of dose over 1-2 minutes IV
    • remainder of dose is given over 1 hour
  • NO aspirin or heparin with 1st 24 hours after tPA
• pulmonary emobolus
  • 50 mg total dose (max)
  • 10 ug bolus followed by 40 mg infusion over 2 hours
  • 0.5 mg/kg total dose for patients weighing <50 kg

* Intravenous (IV) heparin should be used in conjunction with t-PA for the 1st 48 hours after thrombolysis. Heparin infusion is adjusted to achieve aPTT of 50-70 sec.

Pharmacokinetics

• thrombolytic & fibrinolytic activity is dose-dependent
• rapid onset of action
• metabolized by the liver
• excreted in the urine
• distribution phase is approximately 5 minutes
• 1/2life is approximately 26 mintues

Adverse effects

• bleeding
• bruising
• cerebral bleeding (within 36 hours)
  • 0.4-0.7%
  • risk increased with unsuccessful recanalization
• alteplase associated with higher mortality in 1st week after ischemic stroke, but lower mortality thereafter
• hypotension
• allergic reactions
• muscle pain
• fever
• reperfusion arrhythmias
• nausea/vomiting

Mechanism of action

• relatively fibrin-selective plasminogen activator
• minimizes systemic lytic states

Notes

• if blood pressure rises above 180/105 mm Hg after treatment with alteplase intravenous labetalol is indicated
  • continuous infusion of nicardipine if labetalol fails to achieve BP goal

More general terms

• recombinant tissue plasminogen activator (TPA, t-PA, rt-PA,)

Additional terms

• reteplase (Retevase)
• tenecteplase (TNKase)
• thrombolytic therapy