PACKAGE LEAFLET: INFORMATION FOR_

THE USER

Actilyse® Powder and solvent for solution for injection and infusion 10 mg, 20 mg and 50 mg

alteplase

Read all of this leaflet carefully before you start using this medicine.

-    Keep this leaflet. You may need to read it again.

-    If you have any further questions, ask your doctor.

-    This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

-    If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

In this leaflet:

1.    What Actilyse is and what it is used for

2.    Before you receive Actilyse

3.    How is Actilyse administered

4.    Possible side effects

5.    How to store Actilyse

6.    Further information

1. WHAT ACTILYSE IS AND WHAT IT IS USED FOR

The active substance in Actilyse is alteplase (see section 6: “Further information”). It belongs to a group of medicines called thrombolytic agents. These medicines act by dissolving blood clots that have formed in blood vessels.

Actilyse is used to treat a number of conditions caused by blood clots forming within blood vessels, including:

-    heart attacks caused by blood clots in the arteries of the heart (myocardial infarction)

-    blood clots in the arteries of the lungs (pulmonary embolism)

-    stroke caused by a blood clot in an artery of the brain (acute ischaemic stroke)

2. BEFORE YOU RECEIVE ACTILYSE Actilyse will not be given by your doctor

-    if you are allergic (hypersensitive) to the active substance alteplase, to gentamicin (a trace residue from the manufacturing process), to natural rubber (also called latex which is part of the packaging material) or to any of the other ingredients of this medicine (listed in section 6)

-    if you have, or have recently had, an illness that increases your risk of bleeding, including:

•    a bleeding disorder or tendency to bleed

•    a severe or dangerous bleed in any part of the body

•    bleeding within the brain or skull

•    uncontrolled, very high blood pressure

•    bacterial infection or inflammation of the heart (endocarditis), or inflammation of the membranes around the heart (pericarditis)

•    inflammation of the pancreas (acute pancreatitis)

•    gastric ulcer or ulcers in the gut

•    varicose veins in the gullet (oesophageal varices)

•    abnormalities of the blood vessels, such as a localised swelling of an artery (aneurysm)

•    certain tumours

•    severe liver disease

-    if you are taking a medicine used to “thin” the blood (oral anticoagulants), unless appropriate tests confirmed no clinically relevant activity of such medicine

-    if you have ever had surgery to your brain or spine

-    if you have had major surgery or significant injury in the past 3 months

-    if you have been given external heart massage in the past 10 days

-    if you have had a baby in the past 10 days

Your doctor will also not use Actilyse for the treatment of heart attacks or blood clots in the arteries of the lungs

-    if you have or have ever had a stroke caused by bleeding in the brain (haemorrhagic stroke)

-    if you have or have ever had a stroke of unknown cause

-    if you have recently (in the past 6 months) had a stroke caused by a blood clot in an artery of the brain (ischaemic stroke), unless this is the stroke you are about to be treated for

In addition your doctor will not use Actilyse for the treatment of a stroke caused by a blood clot in an artery of the brain (acute ischaemic stroke)

-    if the symptoms of your stroke began more than 4.5 hours ago or if it may be possible that the symptoms began more than 4.5 hours ago, because you do not know when they began

-    if your stroke is causing only very mild symptoms

-    if there are signs of bleeding in the brain

-    if you have had a stroke within the last three months

-    if the symptoms are rapidly improving before receiving Actilyse

-    if you have a very severe stroke

-    if you had cramps (convulsions) when your stroke started

-    if your thromboplastin time (a blood test to see how well your blood clots) is abnormal. This test can be abnormal if you have received heparin (a medicine used to “thin” the blood) within the previous 48 hours

-    if you are diabetic and have ever had a stroke before

-    if the number of blood platelets (thrombocytes) in your blood is very low

-    if you have a very high blood pressure (above 185/110) which can only be reduced by injection of medicines

-    if the amount of sugar (glucose) in your blood is very low (under 50 mg/dl)

-    if the amount of sugar (glucose) in your blood is very high (over 400 mg/dl)

-    if you are under 18 years or over 80 years of age

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Your doctor will take special care with Actilyse

-    if you have had any allergic reaction other than a sudden life-threatening allergic reaction (severe hypersensitivity) to the active substance alteplase, to gentamicin (a trace residue from the manufacturing process), to natural rubber (also called latex which is part of the packaging material) or to any of the other ingredients of this medicine (listed in section 6)

-    if you have or have recently had any other conditions that increase your risk of bleeding, such as:

•    small injury

•    biopsy (a procedure for obtaining a tissue specimen)

•    puncture of major vessels

•    intramuscular injection

-    if you have ever received Actilyse before

-    if you are over 65 years of age

Taking other medicines

Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. It is particularly important that you tell your doctor if you are taking or have recently taken:

-    any medicines which are used to “thin” the blood, including:

•    aspirin

•    warfarin

•    coumarin

•    heparin

-    certain medicines used to treat high blood pressure (ACE inhibitors)

Pregnancy and breast-feeding

Ask your doctor for advice before taking any medicine. Your doctor will only give you Actilyse if the possible benefit outweighs the possible risk to your baby.

3. HOW IS ACTILYSE ADMINISTERED

Actilyse will be administered to you by your doctor or by a health care professional. It is not for self-administration.

Treatment with Actilyse should be initiated as soon as possible after the start of your symptoms.

There are three different conditions for which this medicine can be given:

Heart attack (myocardial infarction)

The dose you are given depends on your body weight. The maximum dose of Actilyse is 100 mg but will be lower if you weigh less than 65 kg. It can be administered in two different ways:

a)    The 90 minute form of administration, for patients treated within 6 hours after start of their symptoms. This consists of:

-    an initial injection of part of the dose of Actilyse into a vein

-    infusions of the remainder of the dose over the following 90 minutes

b)    The 3 hour form of administration, for patients treated 6 to 12 hours after start of their symptoms. This consists of:

-    an initial injection of part of the dose of Actilyse into a vein

-    infusions of the remainder of the dose over the following 3 hours

In addition to Actilyse your doctor will give you another medicine to stop the blood clotting. This will be given as soon as possible after your chest pain starts.

Blood clots in the arteries of the lungs (pulmonary embolism)

The dose you are given depends on your body weight. The maximum dose of Actilyse is 100 mg but will be lower if you weigh less than 65 kg. The medicine is usually given as:

-    an initial injection of part of the dose into a vein

-    an infusion of the remainder of the dose over the following 2 hours

After the treatment with Actilyse, your doctor will start (or resume) therapy with heparin (a medicine to “thin” the blood).

Stroke caused by a blood clot in an artery of the brain (acute ischaemic stroke)

Actilyse must be given within 4.5 hours of the first symptoms. The earlier you receive Actilyse, the more you can benefit from the treatment and the less likely are harmful side effects to occur. The dose you are given depends on your body weight. The maximum dose of this medicine is 90 mg but will be lower if you weigh less than 100 kg. Actilyse is given as:

-    an initial injection of part of the dose into a vein

-    an infusion of the remainder of the dose over the following 60 minutes

You should not take aspirin for the first 24 hours after your treatment with Actilyse for a stroke. Your doctor may give you an injection with heparin if this is necessary.

Method of administration

Actilyse is supplied as a powder and solvent for solution for injection or infusion. This means that each pack contains one vial with powder and one vial with the solvent (water for injections). Before use, the solvent is added to the powder to form a solution ready for administration. This solution is given into a vein (intravenous injection or infusion).

Actilyse should not be mixed with other medicines.

If you have any further questions on the use of Actilyse, ask your doctor.

4. POSSIBLE SIDE EFFECTS

6. FURTHER INFORMATION

Like all medicines, Actilyse can cause side effects, although not everybody gets them. The side effects described below have been experienced by people given Actilyse. Your treatment may be stopped by your doctor if any of the following side effects occur:

-    bleeding in the brain (cerebral haemorrhage) after the treatment of a stroke caused by a blood clot in an artery of the brain (acute ischaemic stroke)

-    cessation of heartbeat (cardiac arrest)

-    shock (a very low blood pressure) due to heart failure

-    bleeding in the respiratory tract, such as nosebleeds (epistaxis) or blood stained phlegm (haemoptysis)

-    bleeding in the brain (cerebral haemorrhage) after the treatment of heart attacks (myocardial infarction) or blood clots in the arteries of the lungs (pulmonary embolism)

-    bleeding into the membranous sac surrounding the heart (haemopericardium)

-    internal bleeding into the back part of the abdomen (retroperitoneal bleeding)

-    damage to the heart valves (mitral regurgitation) or to the wall dividing the heart chambers (ventricular septal defect)

-    bleeding in internal organs, e.g. bleeding in the liver (hepatic haemorrhage) or in the lung (pulmonary haemorrhage)

-    formation of cholesterol crystal clots which can travel to other organs in the body (cholesterol crystal embolisation). The symptoms will depend on the organ affected

-    serious allergic reaction (e.g. life-threatening anaphylaxis, difficulty breathing (bronchospasm), fluid under the skin (angioedema), low blood pressure or shock)

-    heart failure

The following are other possible side effects that may cause your doctor to stop your treatment but, this will depend on how severe the side effects are:

Very common (occurs in more than 1 in 10 patients receiving the medicine)

-    fluid on the lungs (pulmonary oedema)

-    bleeding or bruising (haematoma) where the injection is given

-    low blood pressure (hypotension)

-    irregular heart beat after the blood supply to the heart has been restored

-    chest pain (angina pectoris)

Common (occurs in less than 1 in 10 patients receiving the medicine)

-    further heart attack

-    bleeding of the gums

-    bleeding in the stomach or gut, including vomiting blood (haematemesis) or blood in the stools (melanea or rectal haemorrhage)

-    bleeding into the body tissues causing purplish bruising (ecchymosis)

-    bleeding from the urinary tract or the reproductive organs, which may lead to blood in your urine (haematuria)

-    bleeding which necessitates a blood transfusion

-    feeling sick (nausea)

-    vomiting

-    fever

Uncommon (occurs in less than 1 in 100 patients receiving the medicine)

-    bleeding from the ear

-    formation of blood clots in the lungs (pulmonary embolism)

-    formation of blood clots in the blood vessels which can travel to other organs in the body (thrombotic embolisation). The symptoms will depend on the organ affected

-    allergic reactions, e.g. hives (urticaria) and rash

Very rare (occurs in less than 1 in 10,000 patients receiving the medicine)

-    bleeding in the eyes (ocular haemorrhage)

-    events which affect the nervous system such as:

•    cramps (convulsions, fits)

•    speech problems

•    confusion or delirium (very severe confusion)

•    anxiety accompanied by restlessness (agitation)

•    depression

•    altered thinking (psychosis)

These disorders often occur in association with a stroke caused by a blood clot or bleeding in the brain.

Tell your doctor immediately if you think you are experiencing any of the side effects.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

What Actilyse contains

-    The active substance is alteplase. Each vial contains 10 mg (corresponding to

5.800.000    IU), 20 mg (corresponding to

11.600.000    IU) or 50 mg (corresponding to 29,000,000 IU) alteplase. Alteplase is produced recombinant DNA technique using a Chinese hamster ovary cell-line

-    The other ingredients are arginine, phosphoric acid (dilute) and polysorbate 80

-    The solvent is water for injections

-    The rubber stopper of the packaging material contains natural rubber (latex)

What Actilyse looks like and contents of the pack

Actilyse is a powder and solvent for solution for injection and infusion. This means that each complete pack contains one vial with powder and one vial with the solvent.

Actilyse is available in the following pack sizes:

-    One vial of powder with 10 mg alteplase and one vial with 10 ml solvent

-    One vial of powder with 20 mg alteplase, one vial with 20 ml solvent and one transfer cannula

-    One vial of powder with 50 mg alteplase, one vial with 50 ml solvent and one transfer cannula

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Boehringer Ingelheim Limited,

Ellesfield Avenue,

Bracknell,

Berkshire, RG12 8Ys United Kingdom

Manufacturer

Boehringer Ingelheim Pharma GmbH & Co. KG Birkendorfer strasse 65 D-88397 Biberach/Riss Germany

This leaflet was last approved in 08/2013.

© Boehringer Ingelheim Limited 2013

5. HOW TO STORE ACTILYSE

Keep out of the reach and sight of children.

Actilyse should not be used after the expiry date which is stated on the vial label and the carton. The expiry date refers to the last day of that month.

Normally you will not be asked to store Actilyse as it will be given to you by your doctor. Do not store above 25°C. store in the original package in order to protect from light.

Once the solution is ready for administration, it should be used immediately. The solution may be stored for 24 hours at 2°C - 8°C or for 8 hours at up to 25°C.

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