What is Actilyse®?
Actilyse® (alteplase or recombinant tissue-type plasminogen activator) is a fibrinolytic agent that acts by activating plasminogen to form plasmin. Plasmin, in turn, degrades fibrin, a component of blood clots. So Actilyse® stimulates the release of plasmin, which breaks up the clots in a blocked vessel, limiting the tissue damage caused by ischaemia.
Actilyse® has been licensed for many years to treat patients with acute myocardial infarction or pulmonary embolism, and it is now well established for use in acute ischaemic stroke.
Chemistry of Actilyse®
Actilyse® (alteplase) is a recombinant DNA-derived version of a naturally occurring tissue plasminogen activator protein normally secreted by human endothelial cells.
- High fibrin specificity (is activated where fibrin is i.e. at the clot)
- Purified glycoprotein with 527 amino acids
- Serine protease: converts plasminogen in the presence of fibrin to plasmin
- Short half-life <5min
- Cleared by the liver
What is the dosage and pharmacokinetic profile of Actilyse®?
In acute ischaemic stroke, the recommended dose of Actilyse® is 0.9 mg per kilogram of body weight (maximum 90 mg) infused intravenously over 60 minutes with 10% of the total dose administered as an initial, intravenous bolus.
Actilyse® shows a dose-linear pharmacokinetic profile. It is rapidly cleared from circulating plasma at a rate of 380 – 570 ml/min. More than 50% of Actilyse® is cleared within 5 minutes and approximately 80% is cleared within 10 minutes, primarily by the liver.
How is Actilyse® supplied?
Actilyse® is supplied in vials as a dry powder and solvent for injection and infusion.
The reconstituted solution contains 1 mg alteplase/1 ml.
- 1 vial with 467 mg powder contains: 10 mg alteplase, or
- 1 vial with 933 mg powder contains: 20 mg alteplase, or
- 1 vial with 2333 mg powder contains: 50 mg alteplase.
The pH of the reconstituted solution is 7.3 +/- 0.5.
Which stroke patients will benefit from treatment with Actilyse®?
The best guide to which patients will benefit from treatment with Actilyse® is provided by the inclusion 2 criteria for the NINDS trial.* It included ischaemic stroke patients with a clearly defined time of symptom onset, a deficit measurable on the National Institutes of Health Stroke Scale (NIHSS) and a base-line computed tomography (CT) scan that showed no evidence of intracranial haemorrhage.
*(National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581-1587.)
What contraindications are there to the use of Actilyse®?
Actilyse® should not be given to patients whose symptoms of ischaemic stroke began more than 3-4.5 hours* prior to infusion start or those in whom time of symptom onset is unknown. In addition, it should not be given to patients who have:
- Minor neurological deficit or symptoms rapidly improving before start of infusion
- Severe stroke as assessed clinically (e.g. NIHSS>25) and/or by appropriate imaging techniques
- Seizure at onset of stroke
- Evidence of intracranial haemorrhage (ICH) on the CT-scan
- Symptoms suggestive of subarachnoid haemorrhage, even if CT-scan is normal
- Administration of heparin within the previous 48 hours and a thromboplastin time exceeding the upper limit of normal for laboratory
- Any history of prior stroke and concomitant diabetes
- Prior stroke within the last 3 months
- A platelet count of below 100,000/mm3
- Systolic blood pressure >185 or diastolic BP >110 mm Hg, or aggressive management (IV medication) necessary to reduce BP to these limits
- A blood glucose 400 mg/dl.
- A high risk of haemorrhage due to a comorbid condition or recent treatment
- Actilyse® is not indicated for the treatment of acute stroke in:
- Paediatric patients under 18 years
- Adults over 80 years of age*
*Please check your local regulations for the approved time window allowed and restrictions on treating patients with acute ischaemic stroke with Actilyse®.
A more detailed list of contraindications to Actilyse® is contained in the product's abbreviated prescribing information (see the Prescribing Information section of this website).