METALYSE 10,000 UNITS (50 MG) POWDER AND SOLVENT 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 (hypersensitivity) to tenecteplasa, 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
• stroke (cerebrovascular accident)
• very high blood pressure, not controlled
• a recent head injury
• severe liver disease
• a stomach ulcer (peptic ulcer)
• varices (enlarged veins) in the gullet (oesophageal varices)
• blood vessel abnormalities (e.g. an aneurysm)
• certain tumours
• inflammation of the sac surrounding the heart (pericarditis); inflammation or infection of the heart valves (endocarditis)
• dementia;

• if you are taking medicines to "thin" the blood, such as warfarin (anticoagulants);
• if you have an inflamed pancreas (pancreatitis);
• if you have recently had major surgery, including brain or spinal surgery;
• if you have had cardiopulmonary resuscitation (chest compressions) for more than 2 minutes in the last 2 weeks.

Warnings and precautions

Your doctor will be careful when giving you Metalyse

• if you have had any allergic reaction other than a severe allergic reaction (hypersensitivity) to tenecteplasa, 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 high blood pressure;
• if you have problems with blood circulation in the brain (cerebrovascular disease);
• if you have had bleeding in the gut or urinary tract in the last 10 days (this could cause blood in your stools or urine);
• if you have a heart valve abnormality (e.g. mitral stenosis) with an irregular heartbeat (e.g. atrial fibrillation);
• if you have had an intramuscular injection in the last 2 days;
• if you are over 75 years old;
• if you weigh less than 60 kg;
• 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.

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 being given this medicine.

3. How Metalyse is given

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

Your doctor will give you a medicine to prevent blood clotting, as well as Metalyse, as soon as possible after your chest pain starts.

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 chest pain, 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 given 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 see blood in your urine)
• bruising
• gastrointestinal bleeding (e.g. bleeding from the stomach or intestines)

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

• irregular heartbeats (reperfusion arrhythmias), which can occasionally lead to cardiac arrest. Cardiac arrest can be life-threatening.
• internal bleeding in the abdomen (retroperitoneal bleeding)
• bleeding in the brain (cerebral bleeding). After a brain bleed or other serious bleeding events, death or permanent disability can occur.

• bleeding in the eyes (ocular bleeding)

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

• low blood pressure (hypotension)
• bleeding in the lungs (pulmonary bleeding)
• allergic reactions (anaphylactoid reactions), e.g. rash, hives, 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

As with other thrombolytic agents, the following events have been described as a consequence of myocardial infarction and/or thrombolytic administration:

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

• low blood pressure (hypotension)
• irregular heartbeats
• chest pain (angina)

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 heart lining
• fluid in the lungs (pulmonary oedema)

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

• cardiac arrest
• problems with the heart valves or heart lining (mitral regurgitation, pericardial effusion)
• blood clots in the veins (venous thrombosis)
• fluid between the heart lining and the heart (cardiac tamponade)
• tear in 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 can be life-threatening and may lead to death.

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

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse. This includes any possible side effects 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 the pack in the outer carton to protect from light.

After reconstitution, 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 injection solution immediately.

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

6. Contents of the pack 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. 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 ingredients are arginine, phosphoric acid, and polysorbate 20.
• The solvent is water for injections.
• It contains gentamicin as a residual substance from the manufacturing process.

Appearance and pack contents

The pack contains:

• a vial with 40 mg of tenecteplase as a lyophilised powder, a pre-filled syringe with 8 ml of solvent, and a vial adapter.

or

• a vial with 50 mg of tenecteplase as a lyophilised powder, a pre-filled syringe with 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

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 representative of the marketing authorisation holder:

Date of last revision of this leaflet:

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.