Alteplase
Actilyse
Fibrin-specific plasminogen activator that dissolves fresh thrombus and is the standard thrombolytic for ischaemic stroke and haemodynamically significant pulmonary embolism. The dosing regimens differ entirely between indications — stroke is weight-based, pulmonary embolism and myocardial infarction use a fixed 100 mg — and confusing them is the most common serious error. The short half-life means the effect cannot be reversed once the dose is given.
Intracranial haemorrhage is the lethal complication, occurring in up to 15 percent after stroke thrombolysis, some of which are symptomatic. Never give in active bleeding, known intracranial haemorrhage, INR above 1.7, platelets below 100 × 10⁹/l, or blood pressure above 185/110 mmHg — pressure must be lowered before, not during, the infusion.
Dosing in adults
| Indication | Regimen | Comment |
|---|---|---|
| Acute ischaemic stroke | 0,9 mg/kg iv, maximum 90 mg total: 10 % of the dose as bolus over 1 minute, remaining 90 % as infusion over 60 minutes | within 4.5 hours of symptom onset or last known well |
| Pulmonary embolism with haemodynamic compromise | 10 mg iv as bolus over 1–2 minutes, then 90 mg as infusion over 2 hours | in patients weighing less than 65 kg the total dose is maximum 1,5 mg/kg |
| Pulmonary embolism during cardiac arrest or ongoing CPR | 0,6 mg/kg iv over 5–15 minutes, maximum 50 mg as bolus component, then remaining dose as infusion over 90 minutes | continue CPR for 60–90 minutes before considering termination |
| STEMI, accelerated regimen at weight ≥ 65 kg | 15 mg iv as bolus, 50 mg as infusion over 30 minutes, then 35 mg over 60 minutes — total 100 mg over 90 minutes | only when primary PCI cannot be reached within 120 minutes |
| Maximum dose regardless of indication | never more than 100 mg (stroke: never more than 90 mg) | overdose markedly increases the risk of intracranial haemorrhage |
No dose adjustment in renal impairment. Uraemic platelet dysfunction does increase bleeding risk and should be weighed in the indication assessment.
No formal dose adjustment, but severe hepatic failure with coagulopathy, liver cirrhosis, portal hypertension, and oesophageal varices constitutes a contraindication.
Approved from 16 years of age in ischaemic stroke with the same weight-based dosing as adults. Below 16 years no established dosing exists for these indications and treatment follows local paediatric cardiology or neurology protocols.
Do not use the myocardial infarction or pulmonary embolism 100 mg regimen in stroke — the weight-based stroke dose is lower and giving a fixed 100 mg to a stroke patient is a potentially fatal overdose. In suspected aortic dissection, recent intracranial surgery, or ongoing gastrointestinal bleeding, thrombolysis must not be given regardless of how compelling the clinical picture appears.
Pharmacokinetics
- ONSET
- immediate
- t½ (initial)
- 4–5 minutes
- t½ (terminal)
- approximately 40 minutes
- CLEARANCE
- 550–680 ml/min
- METABOLISM
- Hepatic
- FIBRIN SPECIFICITY
- High — activated by fibrin-bound plasminogen
- SYSTEMIC EFFECT
- Fibrinogen fall for 24 hours
- ANTIGENICITY
- None — can be repeated