ACTILYSE

What it is

ACTILYSE is presented as a sterile, white to off-white, lyophilised powder, intended for intravenous administration after reconstitution with sterilised Water for Injections. The active ingredient is alteplase (rch). ACTILYSE is available in 10 mg and 50 mg presentations.

Approved indications

— Lysis of suspected occlusive coronary artery thrombi associated with evolving transmural myocardial infarction in adults, when treatment is initiated as soon as possible after symptom onset, within 12 hours of symptom onset. — Acute massive pulmonary embolism in patients in whom thrombolytic therapy is considered appropriate. — Thrombolytic treatment of acute ischaemic stroke, when treatment is started as early as possible within 4.5 hours after onset of stroke symptoms and after exclusion of intracranial haemorrhage by appropriate imaging techniques.

Dosing overview

For acute myocardial infarction using accelerated infusion, patients weighing 65 kg or more receive a total dose of 100 mg (15 mg intravenous bolus, followed by 50 mg over 30 minutes, then 35 mg over 60 minutes), while patients weighing less than 65 kg receive a weight-adjusted dose. For acute massive pulmonary embolism, patients weighing 65 kg or more receive a total dose of 100 mg over 2 hours (10 mg bolus over 1–2 minutes, then 90 mg infusion over 2 hours), while patients weighing less than 65 kg receive weight-adjusted dosing up to 1.5 mg/kg over 2 hours. For acute ischaemic stroke, the recommended total dose is 0.9 mg alteplase per kilogram of bodyweight (maximum 90 mg), starting with 10% as an intravenous bolus, followed by the remainder infused over 60 minutes.

Key safety warnings

The most common complication with ACTILYSE is bleeding, which can be internal (at any site or body cavity) or superficial (at invaded or disturbed sites such as venous cutdowns or arterial punctures). Should serious bleeding occur, particularly cerebral haemorrhage, the infusion of ACTILYSE and any concomitant heparin should be terminated immediately. A total dose exceeding 100 mg should not be used for acute myocardial infarction or acute massive pulmonary embolism because it has been associated with an increase in intracranial bleeding. For acute ischaemic stroke, the total dose should not exceed 90 mg. Intracerebral haemorrhage represents a major adverse event in acute ischaemic stroke (up to approximately 15% of patients), with patients treated with ACTILYSE having a significantly increased risk of intracranial haemorrhage as bleeding occurs predominantly into the infarcted area. Angio-oedema is the most common hypersensitivity reaction reported with ACTILYSE, with risk enhanced in acute ischaemic stroke and by concomitant treatment with ACE inhibitors. Administration of intravenous heparin or platelet aggregation inhibitors such as aspirin should be avoided in the first 24 hours after treatment with ACTILYSE due to increased haemorrhagic risk in acute ischaemic stroke.

Contraindications

ACTILYSE is contraindicated in patients with known hypersensitivity to alteplase or any of the excipients. Contraindications due to high risk of haemorrhage include significant bleeding disorder within the past 6 months, history or evidence of intracranial haemorrhage, history of central nervous system damage, severe uncontrolled hypertension, recent prolonged or traumatic cardiopulmonary resuscitation, major surgery or significant trauma within the past 3 months, documented ulcerative gastrointestinal disease during the last 3 months, arterial aneurysms or malformations, neoplasm with increased bleeding risk, bacterial endocarditis, pericarditis, acute pancreatitis, haemostatic defects from severe hepatic or renal disease, and concurrent intravenous thrombolytic agents. Patients currently receiving effective oral anticoagulant treatment (such as warfarin sodium with INR greater than 1.3) is a contraindication. For acute ischaemic stroke specifically, contraindications include symptoms beginning more than 4.5 hours prior to infusion start or unknown symptom onset, minor neurological deficit or rapidly improving symptoms, severe stroke (NIHSS greater than 25), seizure at onset, intracranial haemorrhage on CT scan, subarachnoid haemorrhage symptoms, heparin administration within 48 hours with elevated aPTT, history of prior stroke with concomitant diabetes, previous stroke or serious head trauma within 3 months, platelet count below 100,000/mm³, systolic blood pressure greater than 185 mm Hg or diastolic greater than 110 mm Hg, blood glucose less than 50 mg/dL or greater than 400 mg/dL, and age under 18 years.

Regulatory history

ACTILYSE 50 mg powder for injection was first listed on the ARTG on 26 September 1991. ACTILYSE 20 mg powder for injection was first listed on the ARTG on 6 May 1993. ACTILYSE 10 mg powder for injection was first listed on the ARTG on 14 October 1998.