Alteplase (Actilyse)

Alteplase (Actilyse) - The use of thrombolytics is well established in myocardial infarction. They act by activating plasminogen to form plasmin, which degrades fibrin and so breaks up thrombi. Alteplase or tissue-type plasminogen activator (rt-PA) can be used in major pulmonary embolism associated with hypoxia and haemodynamic compromise.Whilst alteplase is more expensive than streptokinase, it is the preferred thrombolytic as it does not worsen hypotension. Severe bleeding is a potential adverse effect of alteplase and requires discontinuation of the thrombolytic and may require administration of coagulation factors and antifibrinolytic drugs (such as tranexamic acid).

Uses:
Major pulmonary embolism
Acute myocardial infarction
Acute stroke

Contraindications:
Recent haemorrhage, trauma or surgery
Coagulation defects
Severe hypertension
Oesophageal varices
Severe liver disease
Acute pancreatitis

Administration:
• Pulmonary embolism
IV: 10 mg, given over 1–2 minutes, followed by IV infusion of 90mg over 2 hours
Dissolve in WFI to a concentration of 1 mg/ml (50-mg vial with 50 ml WFI). Foaming may occur; this will dissipate after standing for a few minutes.
Monitor: BP (treat if systolic BP > 180 mmHg or diastolic BP > 105mmHg)

• Myocardial infarction
Accelerated regimen (initiated within 6 hours of symptom onset), 15 mg IV, then 50 mg IV infusion over 30 min, then 35 mg over 60 min (total dose 100 mg over 90 min); in patients < 65 kg, 15 mg by IV, the IV infusion of 0.75 mg/kg over 30 min, then 0.5 mg/kg over 60 min (max. total dose 100 mg over 90 min)
Myocardial infarction, initiated within 6–12 hours of symptom onset, 10 mg IV, followed by IV infusion of 50 mg over 60 min, then 4 infusions each of 10 mg over 30 min (total dose 100 mg over 3 hours; max. 1.5 mg/kg in patients <65 kg)

• Acute stroke
Treatment must begin within 3 hours of symptom onset. IV: 900 ug/kg (max. 90 mg), initial 10% of dose by IV injection over 3 min, remainder by IV infusion over 60 min.
Not recommended in the elderly over 80 years of age.

How not to use alteplase:
Not to be infused in glucose solution

Adverse effects:
Nausea and vomiting
Bleeding

Cautions:
Acute stroke (risk of cerebral bleed) Diabetic retinopathy (risk of retinal bleeding) Abdominal aortic aneurysm and enlarged left atrium with AF (risk of embolisation)

Organ failure:
Renal: risk of hyperkalaemia
Hepatic: avoid in severe liver failure