Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Metalyse (Boehringer Ingelheim)
vials containing 8000 IU and 10 000 IU
Approved indication: thrombolysis
Australian Medicines Handbook Section 7.3
For more than a decade, patients with acute myocardial infarctions have been treated with infusions of thrombolytic drugs such streptokinase. The aim of treatment is to restore the blood flow through the coronary artery related to the infarct. Research has aimed at developing drugs which restore more blood flow and do not require a prolonged infusion.
Alteplase is a genetically engineered plasminogen activator. (The activation of plasminogen produces plasmin which breaks down the fibrin in the thrombosis.) Tenecteplase has a similar structure to alteplase and is also produced by genetic engineering. The differences in structure give tenecteplase better fibrin specificity and a longer half-life than alteplase.
Tenecteplase can be given by a single bolus injection. This will improve the blood flow through the infarct-related artery in most patients within 90 minutes. The elimination is biphasic with a terminal half-life of approximately two hours. Clearance is by hepatic metabolism.
A large study involving nearly 17 000 patients has compared a bolus of tenecteplase with a 90 minute infusion of alteplase. All the patients were meant to be treated within six hours of developing the symptoms of acute myocardial infarction. They were also given aspirin and heparin. After 30 days a similar proportion of each treatment group had died. The mortality rate for tenecteplase was 6.18%and it was 6.15% for alteplase.1
Fibrinolytic drugs increase the risk of stroke. In the comparative trial 1.78%of the patients given tenecteplase had a stroke compared with 1.66% of the alteplase group. While the frequency of intracranial bleeding was the same for both drugs, tenecteplase caused significantly fewer non-cerebral haemorrhages. Only 4.3% of the tenecteplase group needed a blood transfusion compared with 5.5% of the alteplase group.1
Despite the reduced need for transfusion, haemorrhage is still a common complication. More than 26% of the tenecteplase group had a bleeding complication. Tenecteplase is contraindicated in patients with an increased risk of bleeding. This includes patients with severe hypertension, peptic ulcers within the last three months, those who are taking warfarin and those who have had recent surgery or trauma, including cardiac resuscitation.
Although most patients in the clinical trial were treated soon after their infarction, tenecteplase has been approved for use up to 12 hours later. This matches the indication for alteplase. While tenecteplase seems to have a few advantages over alteplase, its relative cost-effectiveness will determine if it becomes the preferred treatment option.
- ASSENT-2 investigators. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial. Lancet 1999;354:716-22.