METALYSE

Posology Metalyse must be prescribed by physicians experienced in neurovascular care and the use of thrombolytic treatment, with the facilities to monitor that use. 5 hours after last known well and after exclusion of intracranial haemorrhage by appropriate imaging techniques.

The treatment effect is time-dependent; therefore, earlier treatment increases the probability of a favourable outcome. The appropriate presentation of tenecteplase product should be chosen carefully and in line with the indication.

The 25 mg presentation of tenecteplase is only intended for use in acute ischaemic stroke. Metalyse should be administered on the basis of body weight, with a maximum single dose of 5 000 units (25 mg tenecteplase) for the indication acute ischaemic stroke.

Benefit-risk of tenecteplase treatment should be carefully evaluated in patients weighing 50 kg or less due to limited availability of data. 4). Paediatric population The safety and efficacy of Metalyse in children below 18 years of age have not been established.

No data are available. Adjunctive therapy Drugs affecting coagulation/platelet function The safety and efficacy of this regimen with concomitant administration of heparin or platelet aggregation inhibitors such as acetylsalicylic acid during the first 24 hours after treatment with Metalyse have not been sufficiently investigated.

Therefore, administration of intravenous heparin or platelet aggregation inhibitors such as acetylsalicylic acid should be avoided in the first 24 hours after treatment with Metalyse due to an increased haemorrhagic risk. If heparin is required for other indications the dose should not exceed 10 000 IU per day, administered subcutaneously.

Method of administration The reconstituted solution should be administered intravenously and is for immediate use. The reconstituted solution is a clear and colourless to slightly yellow solution. The required dose should be administered as a single intravenous bolus over approximately 5 to 10 seconds.

40 mg and 50 mg vials of tenecteplase are not intended for use in acute ischaemic stroke. 6.

Summary of the safety profile Haemorrhage is the most common undesirable effect associated with the use of tenecteplase. The type of haemorrhage can be superficial at the injection site or internal at any site or body cavity. Death and permanent disability are reported in patients who have experienced bleeding episodes.

Tabulated list of adverse reactions Adverse reactions listed below are classified according to frequency and system organ class. Frequency groupings are defined according to the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000), not known (cannot be estimated from the available data).

Except for the occurrence of ADR reperfusion arrhythmias in the indication acute myocardial infarction and the frequency of ADR intracranial haemorrhage in the indication acute ischaemic stroke, there is no medical reason to assume that the safety profile of Metalyse in the indication acute ischaemic stroke is different from the profile in the indication acute myocardial infarction.

Table 1 displays the frequency of adverse reactions. System organ class Adverse reaction Immune system disorders Rare Anaphylactoid reaction (including rash, urticaria, bronchospasm, laryngeal oedema) Nervous system disorders Very common Intracranial haemorrhage (such as cerebral haemorrhage, cerebral haematoma, haemorrhagic stroke, haemorrhagic transformation stroke, intracranial haematoma, subarachnoid haemorrhage) including associated symptoms as somnolence, aphasia, hemiparesis, convulsion Eye disorders Uncommon Eye haemorrhage Cardiac disorders Rare Pericardial haemorrhage Vascular disorders Very common Haemorrhage Rare Embolism (thrombotic embolisation) Respiratory, thoracic and mediastinal disorders Common Epistaxis Rare Pulmonary haemorrhage Gastrointestinal disorders Common Gastrointestinal haemorrhage (such as gastric haemorrhage, gastric ulcer haemorrhage, rectal haemorrhage, haematemesis, melaena, mouth haemorrhage) Uncommon Retroperitoneal haemorrhage (such as retroperitoneal haematoma) Not known Nausea, vomiting Skin and subcutaneous tissue disorders Common Ecchymosis Renal and urinary disorders Common Urogenital haemorrhage (such as haematuria, haemorrhage urinary tract) General disorders and administration site conditions Common Injection site haemorrhage, puncture site haemorrhage Investigations Rare Blood pressure decreased Not known Body temperature increased Injury, poisoning and procedural complications Not known Fat embolism, which may lead to corresponding consequences in the organs concerned Surgical and medical procedures Not known Transfusion Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

Traceability In order to improve the traceability of biological medicinal products, the trade name and the batch number of the administered product should be clearly recorded. Thrombolytic treatment requires adequate monitoring. Treatment must be performed under the responsibility and follow-up of physicians trained and experienced in neurovascular care and the use of thrombolytic treatments, with the facilities to monitor that use.

2. Bleeding The most common complication encountered during tenecteplase therapy is bleeding. g. 3. As fibrin is lysed during tenecteplase therapy, bleeding from recent puncture site may occur. Therefore, thrombolytic therapy requires careful attention to all possible bleeding sites (including catheter insertion sites, arterial and venous puncture sites, cutdown sites and needle puncture sites).

The use of rigid catheters as well as intramuscular injections and non-essential handling of the patient should be avoided during treatment with tenecteplase. Should serious bleeding occur, in particular cerebral haemorrhage, concomitant heparin administration should be terminated immediately.

Administration of protamine should be considered if heparin has been administered within 4 hours before the onset of bleeding. In the few patients who fail to respond to these conservative measures, judicious use of transfusion products may be indicated.

Transfusion of cryoprecipitate, fresh frozen plasma, and platelets should be considered with clinical and laboratory reassessment after each administration. A target fibrinogen level of 1 g/L is desirable with cryoprecipitate infusion.

Antifibrinolytic agents are available as a last alternative. g. 3 - Prolonged (> 2 minutes) or traumatic cardiopulmonary resuscitation or cardiac massage. Intracerebral haemorrhage represents the major adverse reaction in the treatment of acute ischaemic stroke (up to 19 % of patients without any increase of overall morbidity or mortality).

1 or to gentamicin (a trace residue from the manufacturing process). g. g. e. 2 mM)