Tenecteplase

5 hours from last known well and after exclusion of intracranial haemorrhage.

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.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

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

4 Geriatrics 2025-10 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES ..........................................................................................

2 TABLE OF CONTENTS ............................................................................................................ 2 PART I: HEALTH PROFESSIONAL INFORMATION ....................................................................

4 1 INDICATIONS ............................................................................................................. 1 Pediatrics................................................................................................................

2 Geriatrics ................................................................................................................ 4 2 CONTRAINDICATIONS ................................................................................................

4 3 SERIOUS WARNINGS AND PRECAUTIONS BOX ........................................................... 5 4 DOSAGE AND ADMINISTRATION................................................................................ 1 Dosing Considerations ...........................................................................................

2 Recommended Dose and Dosage Adjustment ...................................................... 3 Reconstitution ........................................................................................................ 4 Administration .......................................................................................................

7 5 OVERDOSAGE............................................................................................................ 7

1 Adverse Reaction Overview Bleeding The most frequent adverse reaction associated with TNKase (tenecteplase for injection) is bleeding (see 7 WARNINGS AND PRECAUTIONS). Should serious bleeding occur, concomitant heparin and antiplatelet therapy should be discontinued.

Death or permanent disability can occur in patients who experience stroke or serious bleeding episodes. 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials, therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. 5 hours of symptom onset and eligible for intravenous thrombolysis as per current guidelines (see 14 CLINICAL TRIALS).

8% were male, and the median NIHSS score was 9. The rates of 24-hour symptomatic intracerebral hemorrhage were similar between the TNKase and ACTIVASE treatment groups. Rates of imaging-identified hemorrhage (assessed blinded to symptom status and treatment allocation) were comparable between the two groups.

There was no difference in the mortality rate between groups. Orolingual angioedema and peripheral bleeding requiring blood transfusion were similar in both groups (see Table 6). Table 6 describes the incidence of key safety outcomes (adverse drug reactions) in patients with AIS in the AcT trial.

8%. 4 Geriatrics). 2% *defined as bleeding requiring blood transfusion or leading to hemodynamic compromise TNKase (tenecteplase for injection) Page 14 of 34 The incidence of non-intracranial major bleeding and the need for blood transfusions were statistically lower in patients treated with TNKase compared to an accelerated infusion of ACTIVASE.

7%) and gastrointestinal tract (1%). Types of major bleeding reported in less than 1% of the patients were urinary tract, puncture site (including cardiac catheterization site), retroperitoneal, respiratory tract, and unspecified. 3%).

Other Adverse Reactions The following serious adverse reactions have been reported among patients receiving TNKase in the ASSENT-2 clinical trial. These reactions are frequent sequelae of the underlying disease, and the effect of TNKase on the incidence of these events is unknown.

These events can be life-threatening and may lead to death. 5 Post-Market Adverse Reactions Adverse events that have been reported during the post-marketing period are consistent with those seen in clinical trials with TNKase.

Metalyse is indicated in adults for the thrombolytic treatment of suspected myocardial infarction with persistent ST elevation or recent left Bundle Branch Block within 6 hours after the onset of acute myocardial infarction (AMI) symptoms.

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.

3 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).

7 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 8 − 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.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

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) - 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 - Bacterial endocarditis, pericarditis - Acute pancreatitis - Severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis - Active ulcerative gastro-intestinal disease - Known arterial aneurysm and/or 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