Prospect: information for the user

Metalyse 5000units (25mg) powder for injectable solution

tenecteplasa

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

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• If you experience adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section4.

1.What is Metalyse and for what it is used

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

3.How Metalyse is administered

4.Possible adverse effects

5.Storage of Metalyse

6.Contents of the package and additional information

Metalyse is composed of powder for injectable solution.

Metalyse belongs to a group of medications called thrombolytics. These medications contribute to the dissolution of blood clots. Tenecteplase is a recombinant specific plasminogen activator for fibrin.

Metalyse is used in adults for the treatment of acute ischemic stroke caused by a blood clot in a cerebral artery when less than 4.5 hours have elapsed since the last time you did not present symptoms of the current stroke.

Metalyse will not be prescribed or administered by your doctor

• if you have previously experienced a sudden allergic reaction that put your life at risk (severe hypersensitivity) to tenecteplase, to any of the other components of this medication (listed in section6) or to gentamicin (a residual substance from the manufacturing process).If treatment with Metalyse is considered necessary, emergency resuscitation resources must be immediately available for use in case of need;

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

• a bleeding disorder or tendency to bleed;
• uncontrolled high blood pressure;
• a head trauma;
• inflammation of the heart's outer layer (pericarditis); inflammation or infection of the heart valves (endocarditis);
• severe liver disease;
• varicose veins in the esophagus (esophageal varices);
• a stomach ulcer (peptic ulcer);
• vascular anomaly (e.g., an aneurysm);
• certain tumors;
• bleeding in the brain or skull;

• if you are taking tablets/capsules to "thin" the blood (anticoagulants), unless a suitable test has confirmed that there is no clinically significant activity of that medication;
• if you have a severe stroke;
• if your stroke only causes mild symptoms;
• if your symptoms improve rapidly before receiving Metalyse;
• if your stroke symptoms began more than 4.5hours ago or if it is possible that your symptoms began more than 4.5hours ago, as you do not know when they began;
• if you had seizures (convulsions) at the onset of your stroke;
• if your prothrombin time (a blood test to see how your blood clots) is abnormal. This test may be abnormal if you have received heparin (a medication used to "thin" the blood) in the 48hours prior;
• if you have diabetes and have previously had a stroke;
• if you have had a stroke in the past three months;
• if the number of platelets (thrombocytes) in your blood is very low;
• if you have very high blood pressure (above 185/110) that can only be reduced by injecting medication;
• if the amount of sugar (glucose) in your blood is very low (below 50mg/dl) or very high (above 400mg/dl);
• if you have recently undergone major surgery, including surgery on the brain or spine;
• if you have recently had a biopsy (a procedure to obtain a tissue sample);
• if you have had cardiopulmonary resuscitation (chest compressions) for more than 2minutes in the past two weeks;
• if you have pancreatitis (inflammation of the pancreas).

Warnings and precautions

Your doctor will take special care with Metalyse

• if you have had any allergic reaction other than sudden allergic reactions that put your life at risk (severe hypersensitivity) to tenecteplase, to any of the other components of this medication (listed in section6) or to gentamicin (a residual substance 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 small injury such as a large vessel puncture or external cardiac massage
• if you weigh less than 60kg;
• if you are over 80years old, you may have a worse outcome regardless of treatment with Metalyse.

However, in general, the benefit-risk ratio of Metalyse in patients over 80years old is positive and age alone is not a barrier to treatment with Metalyse;

• if you have been previously administered Metalyse.

Children and adolescents

Metalyse is not recommended for use in children and adolescents until the age of 18years.

Other medications and Metalyse

Inform your doctor or pharmacist if you are taking, have taken recently or may need to take any other medication. It is especially important to inform your doctor if you are taking or have taken recently:

• any medication used to "thin" the blood;
• certain medications used to treat high blood pressure (ACE inhibitors).

Pregnancy and breastfeeding

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

The doctor calculates your dose of Metalyse according to your body weight, as follows:

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

Your doctor will administer Metalyse as soon as possible after the onset of the stroke, in the form of a single dose.

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

The side effects described below have been experienced by patients who have received Metalyse:

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

• Bleeding
• Brain hemorrhage (cerebral hemorrhage). After a brain hemorrhage or other severe bleeding events, death or permanent disability may occur.

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

• Bleeding at the injection or puncture site
• Nasal bleeding
• 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):

• Internal abdominal bleeding (retroperitoneal hemorrhage)
• Eye bleeding (ocular hemorrhage)

Rare (may affect up to 1 in 10,000 people):

• Low blood pressure (hypotension)
• Lung bleeding (pulmonary hemorrhage)
• Hypersensitivity (anaphylactoid reactions), e.g., rash, urticaria, difficulty breathing (bronchospasm)
• Bleeding around the heart (hemopericardium)
• Clots in the lungs (pulmonary embolism) and in the blood vessels of other organ systems (thrombotic embolism)

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

• Adipose tissue embolism (clots formed by fat)
• Nausea
• Vomiting
• Increased body temperature (fever)
• Blood transfusions as a result of bleeding

In cases of cerebral hemorrhages, side effects related to the nervous system have been described, e.g., drowsiness, speech disorders, paralysis of parts of the body (hemiparesia), and seizures.

Reporting of side effects

If you experience any type of side effect, consult your doctor or nurse, even if it is a possible side effect that does not appear in this prospectus.You can also report them directly through the national notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the label and the box after CAD.

Do not store at a temperature above 86°F.

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

Once reconstituted, Metalyse can be stored for 24 hours at 39°F-58°F and 8 hours at 86°F. However, for microbiological reasons, your doctor will usually use the reconstituted injectable solution immediately.

Medicines should not be disposed of through drains or in the trash.Ask your pharmacist how to dispose ofthe containers and the medications that you no longerneed.This will help protect the environment.

Composition of Metalyse

• The active principle is tenecteplase.

• Each vial contains 50,000 units (250 mg) of tenecteplase. Each ml contains 1,000 units of tenecteplase when reconstituted with 5 ml of water for injectable preparations.

• The other components are arginine, concentrated phosphoric acid, and polisorbate 20.
• It contains gentamicin as a residual substance from the manufacturing process.

Appearance of the product and contents of the package

The box contains a vial with a lyophilized powder containing 250 mg of tenecteplase.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Boehringer Ingelheim International GmbH

Binger Strasse 173

55216 Ingelheim am Rhein

Germany

Responsible for manufacturing

Boehringer Ingelheim Pharma GmbH & Co. KG

Birkendorfer Strasse 65

88397 Biberach/Riss

Germany

Boehringer Ingelheim France

100-104 avenue de France

75013 Paris

France

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Date of the last review of this leaflet:{MM/AAAA}

Other sources of information

The detailed information about this medication 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 website of the European Medicines Agency.