Metalyse

Package leaflet: Information for the user

Metalyse 8 000 units (40 mg) powder and solvent for solution for injection, 10 000 units (50 mg) powder and solvent for solution for injection

tenecteplase
Please read this leaflet carefully before receiving this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Metalyse is and what it is used for
2. What you need to know before receiving Metalyse
3. How Metalyse is administered
4. Possible side 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 is a powder and solvent for solution for injection.
Metalyse belongs to a group of medicines called thrombolytic agents. 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 the heart attack and can contribute to saving lives.

2. What you should know before receiving Metalyse

Your doctor will not prescribe or administer Metalyse to you

• if you have previously had 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 trace from the manufacturing process). However, if treatment with Metalyse is considered necessary, appropriate resuscitation facilities must be immediately available;
• if you have or have recently had a disease that increases your risk of bleeding (haemorrhage), including:
• bleeding disorders or tendency to bleed (haemorrhage)
• stroke (cerebrovascular event)
• uncontrolled very high blood pressure
• head injuries
• severe liver disease
• stomach ulcer (peptic ulcer)
• oesophageal varices (enlarged veins in the oesophagus)
• blood vessel abnormalities (e.g. aneurysm)
• certain tumours
• inflammation of the membrane lining the heart (pericarditis); inflammation or infection of heart valves (endocarditis)
• dementia;
• if you are taking tablets/capsules used to "thin" the blood, such as coumarin derivatives like warfarin (anticoagulants);
• if you have inflammation of the pancreas (pancreatitis);
• if you have recently undergone major surgery, including brain or spinal surgery;
• if you have undergone cardiopulmonary resuscitation (chest compressions) for more than 2 minutes within the past two weeks.

Warnings and precautions
Your doctor will exercise particular caution when using Metalyse

• if you have previously had any allergic reaction other than 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 trace from the manufacturing process);
• if you have high blood pressure;
• if you have circulatory disorders affecting the brain (cerebrovascular disease);
• if you have had gastrointestinal (intestinal) or genitourinary bleeding within the last ten days (this could cause blood in stools or urine);
• if you have a heart valve abnormality (e.g. mitral valve stenosis) associated with an irregular heartbeat (e.g. atrial fibrillation);
• if you have received an intramuscular injection within the last 2 days;
• if you are over 75 years old;
• if you weigh less than 60 kg;
• if you have previously received Metalyse.

Children and adolescents
The use of Metalyse in children and adolescents up to the age of 18 years is not recommended.
Other medicines and Metalyse
Inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor before administration of this medicine.

3. How Metalyse is administered

Your doctor will calculate your dose of Metalyse based on your body weight, according to the following scheme:

Your doctor will administer the 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 intravenous injection by a physician experienced in the use of this type of medicine.
Your doctor will give you Metalyse as a single dose as soon as possible after the onset of chest pain.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.

The following side effects have been observed in patients treated with 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
• Nosebleed
• Genitourinary bleeding (you may notice blood in your urine)
• Bruising
• Gastrointestinal bleeding (for example, bleeding from the stomach or intestine)

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

• Irregular heartbeat (reperfusion arrhythmias), which sometimes leads to cardiac arrest. Cardiac arrest can be life-threatening.
• Internal bleeding in the abdomen (retroperitoneal haemorrhage)
• Bleeding in the brain (cerebral haemorrhage). Death or permanent disability may occur as a result of cerebral haemorrhage or other episodes of severe bleeding
• Eye bleeding (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), for example rash, hives, breathing difficulties (bronchospasm)
• Bleeding around the heart (haemopericardium)
• Blood clots in the lungs (pulmonary embolism) and in vessels of other organs (thrombotic embolisation)

Not known (frequency cannot be estimated from the available data):

• Fat embolism (fat-containing clots)
• Nausea
• Vomiting
• Increased 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 thrombolytic agents:

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):

• Recurrent chest pain/angina (recurrent ischaemia)
• Heart attack
• Heart failure
• Shock due to heart failure
• Inflammation of the lining around 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 (mitral valve incompetence, pericardial effusion)
• Blood clot in the veins (venous thrombosis)
• Fluid between the heart lining and the heart (cardiac tamponade)
• Rupture of heart muscle (myocardial rupture)

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

• Blood clot in the lungs (pulmonary embolism)

These cardiovascular events may be life-threatening and may lead to death.

Neurological events have been reported in cases of bleeding in the brain, such as drowsiness (stupor), speech disturbances, paralysis of parts of the body (hemiparesis), and seizures (convulsions).

Reporting of side effects

If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Metalyse

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label and the carton after
"Exp.".
Do not store above 30 °C.
Keep the container in the outer carton to protect the medicine from light.
Once reconstituted, Metalyse may be stored for 24 hours at 2–8 °C and for 8 hours at 30 °C.
However, for microbiological reasons, your doctor will, as a matter of practice, use the reconstituted
injectable solution immediately.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package Contents and Other Information

What Metalyse Contains

• The active substance is tenecteplase.
• Each vial contains 8,000 units (40 mg) of tenecteplase. Each pre-filled syringe contains 8 mL of solvent. When reconstituted with 8 mL of solvent, each mL contains 1,000 U of tenecteplase.

or

• Each vial contains 10,000 units (50 mg) of tenecteplase. Each pre-filled syringe contains 10 mL of solvent. When reconstituted with 10 mL of solvent, each mL contains 1,000 U of tenecteplase.
• The other components are arginine, concentrated phosphoric acid, polysorbate 20.
• The solvent is water for injections.
• Gentamicin is present as a residual trace from the manufacturing process.

Description of the Appearance of Metalyse and Contents of the Pack
The pack contains:

• one vial with a lyophilized powder containing 40 mg of tenecteplase, one ready-to-use pre-filled syringe containing 8 mL of solvent, and a vial adapter, or
• one vial with a lyophilized powder containing 50 mg of tenecteplase, one ready-to-use pre-filled syringe containing 10 mL of solvent, and a vial adapter.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Boehringer Ingelheim International GmbH
Binger Strasse 173
55216 Ingelheim am Rhein
Germany

Manufacturers
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 about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Boehringer Ingelheim SComm Boehringer Ingelheim RCV GmbH & Co KG
Tél/Tel: +32 2 773 33 11 Lietuvos filialas
Tel: +370 5 2595942

България Luxembourg/Luxemburg
Бьорингер Ингелхайм РЦВ ГмбХ и Ко. КГ - Boehringer Ingelheim SComm
клон България Tél/Tel: +32 2 773 33 11
Тел: +359 2 958 79 98

Česká republika Magyarország
Boehringer Ingelheim spol. s r.o. Boehringer Ingelheim RCV GmbH & Co KG
Tel: +420 234 655 111 Magyarországi Fióktelepe
Tel: +36 1 299 89 00

Danmark Malta
Boehringer Ingelheim Danmark A/S Boehringer Ingelheim Ireland Ltd.
Tlf: +45 39 15 88 88 Tel: +353 1 295 9620

Deutschland Nederland
Boehringer Ingelheim Pharma GmbH & Co. KG Boehringer Ingelheim B.V.
Tel: +49 (0) 800 77 90 900 Tel: +31 (0) 800 22 55 889

Eesti Norge
Boehringer Ingelheim RCV GmbH & Co KG Boehringer Ingelheim Norway KS
Eesti filiaal Tlf: +47 66 76 13 00
Tel: +372 612 8000

Ελλάδα Österreich
Boehringer Ingelheim Ελλάς Μονοπρόσωπη A.E. Boehringer Ingelheim RCV GmbH & Co KG
Tηλ: +30 2 10 89 06 300 Tel: +43 1 80 105-7870

España Polska
Boehringer Ingelheim España, S.A. Boehringer Ingelheim Sp. z o.o.
Tel: +34 93 404 51 00 Tel: +48 22 699 0 699

France Portugal
Boehringer Ingelheim France S.A.S. Boehringer Ingelheim Portugal, Lda.
Tél: +33 3 26 50 45 33 Tel: +351 21 313 53 00

Hrvatska România
Boehringer Ingelheim Zagreb d.o.o. Boehringer Ingelheim RCV GmbH & Co KG
Tel: +385 1 2444 600 Vienna - Bucharest Branch
Tel: +40 21 302 28 00

Ireland Slovenija
Boehringer Ingelheim Ireland Ltd. Boehringer Ingelheim RCV GmbH & Co KG
Tel: +353 1 295 9620 Podružnica Ljubljana
Tel: +386 1 586 40 00

Ísland Slovenská republika
Vistor hf. Boehringer Ingelheim RCV GmbH & Co KG
Sími: +354 535 7000 organisational unit
Tel: +421 2 5810 1211

Italia Suomi/Finland
Boehringer Ingelheim Italia S.p.A. Boehringer Ingelheim Finland Ky
Tel: +39 02 5355 1 Puh/Tel: +358 10 3102 800

Κύπρος Sverige
Boehringer Ingelheim Ελλάς Μονοπρόσωπη A.E. Boehringer Ingelheim AB
Tηλ: +30 2 10 89 06 300 Tel: +46 8 721 21 00

Latvija United Kingdom (Northern Ireland)
Boehringer Ingelheim RCV GmbH & Co KG Boehringer Ingelheim Ireland Ltd.
Latvijas filiāle Tel: +353 1 295 9620
Tel: +371 67 240 011

Other Sources of Information
More detailed information on this medicinal product is available on the website of the European Medicines Agency, http://www.ema.europa.eu.
This leaflet is available in all languages of the European Union/European Economic Area on the European Medicines Agency website.

Package leaflet: information for the user

Metalyse 5,000 units (25 mg) powder for solution for injection

tenecteplase
Please read this leaflet carefully before receiving this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you experience any side effects, including those not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Metalyse is and what it is used for
2. What you need to know before receiving Metalyse
3. How Metalyse is administered
4. Possible side 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 is a powder for injectable solution.
Metalyse belongs to a group of medicines called thrombolytic agents. These medicines help dissolve blood clots. Tenecteplase is a recombinant fibrin-specific plasminogen activator.
Metalyse is used in adults for the treatment of stroke caused by a blood clot in an artery of the brain (acute ischemic stroke) when less than 4.5 hours have passed since the onset of stroke symptoms.

2. What you should know before receiving Metalyse

Your doctor will not prescribe or administer Metalyse to you

• 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 trace from the manufacturing process). However, if treatment with Metalyse is considered necessary, appropriate resuscitation facilities must be immediately available in case of emergency;
• if you have or have recently had a disease that increases your risk of bleeding (haemorrhage), including:
• bleeding disorders or tendency to bleed (haemorrhage);
• uncontrolled, very high blood pressure;
• head injury;
• inflammation of the membrane lining the heart (pericarditis); inflammation or infection of the heart valves (endocarditis);
• severe liver disease;
• oesophageal varices (enlarged veins in the oesophagus);
• stomach ulcer (peptic ulcer);
• blood vessel abnormalities (e.g. aneurysm);
• certain tumours;
• bleeding within the brain or skull;
• if you are taking tablets/capsules used to "thin" the blood (anticoagulants), unless a specific test confirms the absence of clinically relevant activity of that medicine;
• if you have a very severe stroke;
• if your stroke causes only mild symptoms;
• if your symptoms are rapidly improving before receiving Metalyse;
• if your stroke symptoms began more than 4.5 hours ago, or if it is possible that symptoms started more than 4.5 hours ago because you do not know when they began;
• if you had seizures when your stroke started;
• if you have an abnormal prothrombin time (a blood test measuring blood clotting ability). This test may be abnormal if you have received heparin (a medicine used to "thin" the blood) within the previous 48 hours;
• if you have diabetes and have previously had a stroke;
• if you have had a stroke within the last three months;
• if you have a very low platelet count (thrombocytes) in your blood;
• if your blood pressure is very high (above 185/110) and can only be reduced by injection of medicines;
• if you have very low blood sugar levels (glucose) (less than 50 mg/dL) or very high levels (more than 400 mg/dL);
• if you have recently undergone major surgery, including brain or spinal surgery;
• if you have recently undergone a biopsy (a procedure used to collect a tissue sample);
• if you have undergone cardiopulmonary resuscitation (chest compressions) for more than 2 minutes within the past two weeks;
• if you have inflammation of the pancreas (pancreatitis).

Warnings and precautions
Your doctor will exercise particular caution when administering Metalyse

• if you have previously experienced any allergic reaction other than 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 trace from the manufacturing process);
• if you have or have recently had any other condition that increases the risk of bleeding, for example:
• an intramuscular injection;
• a minor injury, such as puncture of a large blood vessel or external cardiac massage;
• if you weigh less than 60 kg;
• if you are over 80 years of age, you may have a less favourable outcome regardless of treatment with Metalyse. However, in general, the benefit-risk ratio of Metalyse in patients over 80 years of age is positive, and age alone should not be a barrier to treatment with Metalyse;
• if you have previously received Metalyse.

Children and adolescents
The use of Metalyse in children and adolescents up to the age of 18 years is not recommended.
Other medicines and Metalyse
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. It is particularly important that you inform your doctor if you are taking or have recently taken:
any medicine used to "thin" the blood;
certain medicines used to treat high blood pressure (ACE inhibitors).
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor for advice before this medicine is administered to you.

3. How Metalyse is administered

Your doctor calculates your dose of Metalyse based on your body weight, according to the following scheme:

Metalyse is administered as a single intravenous injection by a physician experienced in the use of
this type of medicinal product.
Your doctor will give you Metalyse as a single dose as soon as possible after the onset of stroke.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
The following side effects have been reported in patients treated with Metalyse:

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

• Bleeding
• Bleeding in the brain (cerebral haemorrhage). Cerebral haemorrhage or other episodes of severe bleeding may result in death or permanent disability

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. bleeding from the stomach or intestines)

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

• Internal bleeding in the abdomen (retroperitoneal haemorrhage)
• Eye bleeding (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), for example rash, urticaria, breathing difficulties (bronchospasm)
• Bleeding around the heart (haemopericardium)
• Blood clots in the lungs (pulmonary embolism) and in blood vessels of other organs (thrombotic embolisation)

Not known (frequency cannot be estimated from the available data):

• Fat embolism (fatty clots)
• Nausea
• Vomiting
• Increased body temperature (fever)
• Blood transfusions as a consequence of bleeding

Neurological events have been reported in cases of bleeding in the brain, for example drowsiness (lethargy), speech disorders, paralysis of parts of the body (hemiparesis), and seizures (convulsions).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store 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 carton after "Exp.".
Do not store above 30 °C.
Keep the container in the outer carton to protect the medicine 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, as a standard practice, your doctor will use the reconstituted injectable solution immediately.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Metalyse contains

• The active substance is tenecteplase.
• Each vial contains 5,000 units (25 mg) of tenecteplase. When reconstituted with 5 mL of water for injections, each mL contains 1,000 IU of tenecteplase.
• The other components are arginine, concentrated phosphoric acid, polysorbate 20.
• Gentamicin is present as a residual trace from the manufacturing process.

Description of the appearance of Metalyse and contents of the pack
The pack contains one vial with a lyophilized powder containing 25 mg of tenecteplase.

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 about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Boehringer Ingelheim SComm Boehringer Ingelheim RCV GmbH & Co KG
Tél/Tel: +32 2 773 33 11 Lietuvos filialas
Tel: +370 5 2595942

България Luxembourg/Luxemburg
Бьорингер Ингелхайм РЦВ ГмбХ и Ко. КГ - Boehringer Ingelheim SComm
клон България Tél/Tel: +32 2 773 33 11
Тел: +359 2 958 79 98

Česká republika Magyarország
Boehringer Ingelheim spol. s r.o. Boehringer Ingelheim RCV GmbH & Co KG
Tel: +420 234 655 111 Magyarországi Fióktelepe
Tel: +36 1 299 89 00

Danmark Malta
Boehringer Ingelheim Danmark A/S Boehringer Ingelheim Ireland Ltd.
Tlf: +45 39 15 88 88 Tel: +353 1 295 9620

Deutschland Nederland
Boehringer Ingelheim Pharma GmbH & Co. KG Boehringer Ingelheim B.V.
Tel: +49 (0) 800 77 90 900 Tel: +31 (0) 800 22 55 889

Eesti Norge
Boehringer Ingelheim RCV GmbH & Co KG Boehringer Ingelheim Norway KS
Eesti filiaal Tlf: +47 66 76 13 00
Tel: +372 612 8000

Ελλάδα Österreich
Boehringer Ingelheim Ελλάς Μονοπρόσωπη A.E. Boehringer Ingelheim RCV GmbH & Co KG
Tηλ: +30 2 10 89 06 300 Tel: +43 1 80 105-7870

España Polska
Boehringer Ingelheim España, S.A. Boehringer Ingelheim Sp. z o.o.
Tel: +34 93 404 51 00 Tel: +48 22 699 0 699

France Portugal
Boehringer Ingelheim France S.A.S. Boehringer Ingelheim Portugal, Lda.
Tél: +33 3 26 50 45 33 Tel: +351 21 313 53 00

Hrvatska România
Boehringer Ingelheim Zagreb d.o.o. Boehringer Ingelheim RCV GmbH & Co KG
Tel: +385 1 2444 600 Viena - Sucursala Bucureşti
Tel: +40 21 302 28 00

Ireland Slovenija
Boehringer Ingelheim Ireland Ltd. Boehringer Ingelheim RCV GmbH & Co KG
Tel: +353 1 295 9620 Podružnica Ljubljana
Tel: +386 1 586 40 00

Ísland Slovenská republika
Vistor hf. Boehringer Ingelheim RCV GmbH & Co KG
Sími: +354 535 7000 organizačná zložka
Tel: +421 2 5810 1211

Italia Suomi/Finland
Boehringer Ingelheim Italia S.p.A. Boehringer Ingelheim Finland Ky
Tel: +39 02 5355 1 Puh/Tel: +358 10 3102 800

Κύπρος Sverige
Boehringer Ingelheim Ελλάς Μονοπρόσωπη A.E. Boehringer Ingelheim AB
Tηλ: +30 2 10 89 06 300 Tel: +46 8 721 21 00

Latvija United Kingdom (Northern Ireland)
Boehringer Ingelheim RCV GmbH & Co KG Boehringer Ingelheim Ireland Ltd.
Latvijas filiāle Tel: +353 1 295 9620
Tel: +371 67 240 011

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.
This leaflet is available in all languages of the European Union/European Economic Area on the European Medicines Agency website.