METALYSE

Posology Metalyse should be prescribed by physicians experienced in the use of thrombolytic treatment and with the facilities to monitor that use. Treatment with Metalyse should be initiated as early as possible after onset of symptoms.

The appropriate presentation of tenecteplase product should be chosen carefully and in line with the indication. The 40 mg and 50 mg presentations are only intended for use in acute myocardial infarction. Metalyse should be administered on the basis of body weight, with a maximum dose of 10 000 units (50 mg tenecteplase).

1). Paediatric population The safety and efficacy of Metalyse in children (below 18 years) have not been established. No data are available. Adjunctive therapy Antithrombotic adjunctive therapy with platelet inhibitors and anticoagulants should be administered according to the current relevant treatment guidelines for the management of patients with ST-elevation myocardial infarction.

For coronary intervention see section

Summary of the safety profile Haemorrhage is a very common undesirable effect associated with the use of tenecteplase. The type of haemorrhage is predominantly superficial at the injection site. Ecchymoses are observed commonly but usually do not require any specific action.

Death and permanent disability are reported in patients who have experienced stroke (including intracranial bleeding) and other serious 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).

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 Uncommon 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 Uncommon Reperfusion arrhythmias (such as asystole, accelerated idioventricular arrhythmia, arrhythmia, extrasystoles, atrial fibrillation, atrioventricular first degree to atrioventricular block complete, bradycardia, tachycardia, ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia) occur in close temporal relationship to treatment with tenecteplase.

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 As with other thrombolytic agents, the following events have been reported as sequelae of myocardial infarction and/or thrombolytic administration: - very common: hypotension, heart rate and rhythm disorders, angina pectoris - common: recurrent ischaemia, cardiac failure, myocardial infarction, cardiogenic shock, pericarditis, pulmonary oedema - uncommon: cardiac arrest, mitral valve incompetence, pericardial effusion, venous thrombosis, cardiac tamponade, myocardial rupture - rare: pulmonary embolism These cardiovascular events can be life-threatening and may lead to death.

4. Unfractionated heparin and enoxaparin have been used as antithrombotic adjunctive therapy in clinical studies with Metalyse. Acetylsalicylic acid should be initiated as soon as possible after symptom onset and continued with lifelong treatment unless it is contraindicated.

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 10 seconds.

6. 1 or to gentamicin (a trace residue from the manufacturing process). If treatment with Metalyse is nevertheless considered to be necessary, facilities for resuscitation should be immediately available in case of need. g. e. 4 Special warnings and precautions for use 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.

1 ASSENT-4 study) should not be given. 1 STREAM study). Bleeding The most common complication encountered during tenecteplase therapy is bleeding. The concomitant use of heparin anticoagulation may contribute to bleeding. 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.

Most frequently haemorrhage at the injection site, and occasionally genitourinary and gingival bleeding were observed. Should serious bleeding occur, in particular cerebral haemorrhage, concomitant heparin administration should be terminated immediately.

1 or to gentamicin (a trace residue from the manufacturing process). If treatment with Metalyse is nevertheless considered to be necessary, facilities for resuscitation should be immediately available in case of need. g. e. neoplasm, aneurysm, intracranial or spinal surgery) - Known haemorrhagic diathesis - Severe uncontrolled hypertension - Major surgery, biopsy of a parenchymal organ, or significant trauma within the past 2 months (this includes any trauma associated with the current AMI) - Recent trauma to the head or cranium - Prolonged cardiopulmonary resuscitation (> 2 minutes) within the past 2 weeks - Acute pericarditis and/or subacute bacterial endocarditis - Acute pancreatitis - Severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis - Active peptic ulceration - Arterial aneurysm and known arterial/venous malformation - Neoplasm with increased bleeding risk - Any known history of haemorrhagic stroke or stroke of unknown origin - Known history of ischaemic stroke or transient ischaemic attack in the preceding 6 months - Dementia