Metalyse 10,000 UNITS (50 mg) powder and solvent for solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Metalyse 8000 units (40 mg) powder and solvent for solution for injection

Metalyse 10000 units (50 mg) powder and solvent for solution for injection

tenecteplase

Read all of this leaflet carefully before this medicine is administered to you, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of this leaflet

1. What Metalyse is and what it is used for
2. What you need to know before Metalyse is administered to you
3. How Metalyse is administered
4. Possible adverse effects
5. How to store Metalyse
6. Contents of the pack and other information

1. What Metalyse is and what it is used for

Metalyse consists of powder and solvent for injectable solution.

Metalyse belongs to a group of medicines called thrombolytics. These medicines help dissolve blood clots. Tenecteplase is a recombinant, fibrin-specific plasminogen activator.

Metalyse is used for the treatment of myocardial infarction (heart attack) within 6 hours of the onset of symptoms, and helps dissolve blood clots that have formed in the blood vessels of the heart. This helps prevent damage caused by heart attacks and has been shown to save lives.

2. What you need to know before Metalyse is administered to you

Metalyse will not be prescribed or administered by your doctor

• if you have previously experienced a sudden, life-threatening allergic reaction (severe hypersensitivity) to tenecteplase, to any of the other components of this medicine (listed in section 6), or to gentamicin (a residual substance from the manufacturing process). If treatment with Metalyse is nevertheless considered necessary, resuscitation equipment must be immediately available for use if required;

• if you currently have or have recently had a condition that increases your risk of bleeding (haemorrhage), including:

• a bleeding disorder or tendency to bleed

• stroke caused by bleeding in the brain (haemorrhagic stroke) or stroke of unknown cause

• stroke caused by a blood clot in an artery of the brain (ischaemic stroke) within the previous 6 months

• severely high, uncontrolled blood pressure

• head trauma

• severe liver disease

• gastric or intestinal ulcers

• oesophageal varices (enlarged veins in the oesophagus)

• blood vessel abnormalities (e.g., aneurysm)

• certain tumours

• inflammation of the membrane surrounding the heart (pericarditis); inflammation or infection of the heart valves (endocarditis)

• dementia;

• if you are taking tablets/capsules to "thin" the blood, such as coumarin derivatives like warfarin (anticoagulants);

• if you have inflamed pancreas (pancreatitis);

• if you have recently undergone major surgery, including brain or spinal surgery.

Warnings and precautions

Your doctor will exercise special caution when using Metalyse

• if you have previously experienced any allergic reaction other than sudden, life-threatening allergic reactions (severe hypersensitivity) to tenecteplase, to any of the other components of this medicine (listed in section 6), or to gentamicin (a residual substance from the manufacturing process);
• if you have high blood pressure;
• if you have experienced gastrointestinal or genitourinary bleeding within the last ten days (this could result in blood in stools or urine);
• if you have a heart valve abnormality (e.g., mitral stenosis) with an abnormal heart rhythm (e.g., atrial fibrillation);
• if you have recently received an intramuscular injection;
• if you are 75 years of age or older;
• if you weigh less than 50 kg;
• if you have received cardiopulmonary resuscitation (chest compressions) for more than 2 minutes;
• if you have previously been administered Metalyse.

Children and adolescents

The use of Metalyse is not recommended in children and adolescents under 18 years of age.

Other medicines and Metalyse

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor before this medicine is administered to you.

Metalyse contains polysorbate 20

This medicine contains 3.2 mg or 4.0 mg of polysorbate 20 in each 40 mg or 50 mg vial, respectively. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

3. How Metalyse is administered

The doctor calculates your dose of Metalyse according to your body weight, using the following scheme:

Your doctor will give you a medicine to prevent blood clotting, in addition to Metalyse, as soon as possible after the onset of chest pain.

Metalyse is administered as a single injection into a vein by a doctor experienced in the use of this type of medicine.

Your doctor will give you Metalyse as soon as possible after the onset of your chest pain, as a single dose.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

The following adverse effects have been reported in patients who have received Metalyse:

Very common (may affect more than 1 in 10 people):

• bleeding

Common (may affect up to 1 in 10 people):

• bleeding at the injection or puncture site
• nosebleeds
• genitourinary bleeding (you may notice blood in your urine)
• bruising
• gastrointestinal bleeding (e.g., stomach or intestinal bleeding)

Uncommon (may affect up to 1 in 100 people):

• irregular heartbeat (reperfusion arrhythmias), which occasionally lead to cardiac arrest. Cardiac arrest may be life-threatening.

• internal bleeding in the abdomen (retroperitoneal haemorrhage)

• bleeding in the brain (cerebral haemorrhage). Death or permanent disability may occur following bleeding in the brain or other serious bleeding events.

• bleeding in the eyes (ocular haemorrhage)

Rare (may affect up to 1 in 1,000 people):

• low blood pressure (hypotension)

• bleeding in the lungs (pulmonary haemorrhage)

• hypersensitivity (anaphylactoid reactions), e.g., rash, urticaria, breathing difficulties (bronchospasm)

• bleeding around the heart (haemopericardium)

• blood clots in the lung (pulmonary embolism) and in blood vessels of other organ systems (thrombotic embolism)

Frequency not known (cannot be estimated from available data):

• fat embolism (fat-formed clots)
• nausea
• vomiting
• increase in body temperature (fever)
• blood transfusions as a consequence of bleeding

As with other thrombolytic agents, the following events have been reported as consequences of myocardial infarction and/or administration of thrombolytics:

Very common (may affect more than 1 in 10 people):

• low blood pressure (hypotension)
• irregular heartbeat
• chest pain (angina pectoris)

Common (may affect up to 1 in 10 people):

• additional chest pain/angina (recurrent ischaemia)
• heart attack
• heart failure
• shock due to heart failure
• inflammation of the lining of the heart
• fluid in the lungs (pulmonary oedema)

Uncommon (may affect up to 1 in 100 people):

• cardiac arrest
• problems with the heart valve or lining of the heart (mitral valve regurgitation, pericardial effusion)
• blood clots in the veins (venous thrombosis)
• fluid between the lining of the heart and the heart (cardiac tamponade)
• rupture of the heart muscle (myocardial rupture)

Rare (may affect up to 1 in 1,000 people):

• blood clots in the lungs (pulmonary embolism)

These cardiovascular events may be potentially fatal and may lead to death.

In cases of cerebral haemorrhage, nervous system-related effects have been reported, e.g., somnolence, speech disorders, paralysis of parts of the body (hemiparesis), and seizures.

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Metalyse

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the label and the carton after EXP.

Do not store above 30 °C.

Keep the container in the outer packaging to protect it from light.

After reconstitution, Metalyse may be stored for 24 hours at 2–8 °C and for 8 hours at 30 °C. However, for microbiological reasons, the reconstituted injectable solution is usually used immediately by your doctor.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Metalyse

• The active substance is tenecteplase.

• Each vial contains 8,000 units (40 mg) of tenecteplase. Each pre-filled syringe contains 8 ml of solvent. Each ml contains 1,000 units of tenecteplase when reconstituted with 8 ml of solvent.

or

• Each vial contains 10,000 units (50 mg) of tenecteplase. Each pre-filled syringe contains 10 ml of solvent. Each ml contains 1,000 units of tenecteplase when reconstituted with 10 ml of solvent.

• The other components are arginine, concentrated phosphoric acid (E 338) and polysorbate 20 (E 432).

• The solvent is water for injections.

• Contains gentamicin as a residual substance from the manufacturing process.

Nature of the product and pack contents

The pack contains:

• one vial with a lyophilised powder containing 40 mg of tenecteplase, one pre-filled syringe ready for use containing 8 ml of solvent, and one vial adapter.

or

• one vial with a lyophilised powder containing 50 mg of tenecteplase, one pre-filled syringe ready for use containing 10 ml of solvent, and one vial adapter.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Boehringer Ingelheim International GmbH

Binger Strasse 173

55216 Ingelheim am Rhein

Germany

Manufacturer

Boehringer Ingelheim Pharma GmbH & Co. KG

Birkendorfer Strasse 65

88397 Biberach/Riss

Germany

Boehringer Ingelheim France

100-104 avenue de France

75013 Paris

France

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this leaflet: {MM/YYYY}

Other sources of information

Detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu.

This leaflet is available in all languages of the European Union/European Economic Area on the European Medicines Agency website.