METALYSE 5,000 UNITS (25 MG) POWDER FOR INJECTABLE SOLUTION

2. What you need to know before you are given Metalyse

Metalyse will not be prescribed or given to you by your doctor

• if you have previously had a severe allergic reaction (anaphylaxis) to tenecteplase, to any of the other ingredients of this medicine (listed in section 6) or to gentamicin (a residual substance from the manufacturing process). If treatment with Metalyse is still considered necessary, resuscitation equipment must be available for immediate use if needed;

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

• a bleeding disorder or tendency to bleed;
• very high blood pressure, which is not controlled;
• a head trauma;
• inflammation of the layer surrounding the heart (pericarditis); inflammation or infection of the heart valves (endocarditis);
• severe liver disease;
• varices of the oesophagus;
• a stomach ulcer (peptic ulcer);
• a blood vessel abnormality (e.g. an aneurysm);
• certain tumours;
• bleeding in the brain or skull;

• if you are taking anticoagulant tablets/capsules, unless a suitable test has confirmed that the medicine is not clinically active;
• if you have a very severe stroke;
• if your stroke only causes mild symptoms;
• if your symptoms improve quickly before you receive Metalyse;
• if your stroke symptoms started more than 4.5 hours ago or if it is possible that your symptoms started more than 4.5 hours ago, because you do not know when they started;
• if you had seizures at the start of your stroke;
• if your thromboplastin time (a blood test to see how your blood clots) is abnormal. This test may be abnormal if you have received heparin (a medicine used to thin the blood) in the last 48 hours;
• if you have diabetes and have previously had a stroke;
• if you have had a stroke in the last three months;
• if the number of platelets (thrombocytes) in your blood is very low;
• if you have very high blood pressure (above 185/110 mmHg) that can only be lowered by injecting medicines;
• if the amount of sugar (glucose) in your blood is very low (below 50 mg/dl) or very high (above 400 mg/dl);
• if you have recently undergone major surgery, including brain or spinal surgery;
• 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 2 minutes in the last two weeks;
• if you have pancreatitis.

Warnings and precautions

Your doctor will be particularly careful with Metalyse

• if you have had any allergic reaction other than a severe allergic reaction (anaphylaxis) to tenecteplase, to any of the other ingredients of this medicine (listed in section 6) 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 minor injury such as a puncture of large vessels or external cardiac massage
• if you weigh less than 60 kg;
• if you are over 80 years old, you may have a worse outcome, regardless of treatment with Metalyse.

However, in general, the benefit/risk balance of Metalyse in patients over 80 years old is positive and age alone is not an obstacle to treatment with Metalyse;

• if you have been given Metalyse before.

Children and adolescents

Metalyse is not recommended for use in children and adolescents under 18 years.

Other medicines and Metalyse

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. It is especially important that you tell 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 breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before you are given this medicine.

3. How Metalyse is given

Your doctor will calculate your dose of Metalyse according to your body weight, as follows:

Metalyse is given as a single injection into a vein by a doctor with experience in the use of this type of medicine.

Your doctor will give you Metalyse as soon as possible after the start of your stroke, as a single dose.

4. Possible side effects

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

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

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

• bleeding
• bleeding in the brain (cerebral haemorrhage). After a brain haemorrhage or other serious bleeding events, death or permanent disability may occur.

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

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

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

• internal bleeding in the abdomen (retroperitoneal haemorrhage)
• 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, difficulty breathing (bronchospasm)
• bleeding in the area surrounding the heart (haemopericardium)
• blood clots in the lungs (pulmonary embolism) and in the blood vessels of other organ systems (thrombotic embolisms)

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

• fat embolism (clots formed by fat)
• nausea
• vomiting
• increased body temperature (fever)
• blood transfusions as a result of bleeding

In the case of cerebral haemorrhage, effects related to the nervous system have been described, e.g. drowsiness, speech disorders, paralysis of parts of the body (hemiparesis) and seizures.

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side 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 which is stated on the label and carton after EXP.

Do not store above 30°C.

Store in the original package to protect from light.

Once reconstituted, Metalyse can be stored for 24 hours at 2-8°C and 8 hours at 30°C. However, for microbiological reasons, your doctor will normally use the reconstituted solution immediately.

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

6. Contents of the pack and other information

What Metalyse contains

• The active substance is tenecteplase.

• Each vial contains 50,000 units (25 mg) of tenecteplase. Each ml contains 1,000 units of tenecteplase when reconstituted with 5 ml of water for injections.

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

Appearance and pack contents

The pack contains one vial with 25 mg of tenecteplase as a lyophilised powder.

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

You can get more information about this medicine by contacting the local representative of the marketing authorisation holder:

Date of last revision of this leaflet:{MM/YYYY}

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/.

The leaflet can be found in all EU/EEA languages on the European Medicines Agency website.