Package leaflet: Information for the user In addition your doctor will not use Actilyse for the 3.

How is Actilyse administered 4. Possible side effects Very rare (occurs in less than 1 in 10,000 patients 6. Contents of the pack and other information
treatment of a stroke caused by a blood clot in an receiving the medicine)
artery of the brain (acute ischaemic stroke) Actilyse will be prepared and administered to you by Like all medicines, Actilyse can cause side effects, • events which affect the nervous system such as: What Actilyse contains
Actilyse® powder and
abcd
• if the symptoms of your stroke began more than your doctor or by a health care professional. It is not for although not everybody gets them. The side effects - cramps (convulsions, fits)
4.5 hours ago or if it may be possible that the self-administration. described below have been experienced by people - speech problems • The active substance is alteplase. Each vial contains
solvent for solution for symptoms began more than 4.5 hours ago, because given Actilyse. Your treatment may be stopped by your - confusion or delirium (very severe confusion) 10 mg (corresponding to 5,800,000 IU), 20 mg
you do not know when they began Treatment with Actilyse should be initiated as soon as doctor if any of the following side effects occur: - anxiety accompanied by restlessness (agitation) (corresponding to 11,600,000 IU) or 50 mg
injection and infusion • if your stroke is causing only very mild symptoms possible after the start of your symptoms. - depression (corresponding to 29,000,000 IU) alteplase. The other
• if there are signs of bleeding in the brain • bleeding in the brain (cerebral haemorrhage) after - altered thinking (psychosis) ingredients are arginine, phosphoric acid (dilute) and
10 mg, 20 mg and 50 mg • if you have had a stroke within the last three months There are three different conditions for which this the treatment of a stroke caused by a blood clot in an These disorders often occur in association with a polysorbate 80.
• if the symptoms are rapidly improving before medicine can be given: artery of the brain (acute ischaemic stroke) stroke caused by a blood clot or bleeding in the brain. • The solvent is water for injections.
receiving Actilyse • cessation of heartbeat (cardiac arrest) • The rubber stopper of the packaging material
Alteplase • if you have a very severe stroke Heart attack (myocardial infarction) • shock (a very low blood pressure) due to heart failure Not known (frequency cannot be estimated from contains natural rubber (latex).
• if you had cramps (convulsions) when your stroke The dose you are given depends on your body weight. • bleeding in the brain (cerebral haemorrhage) after available data)
Read all of this leaflet carefully before you start using 1. What Actilyse is and what it is used for started The maximum dose of Actilyse is 100 mg but will be the treatment of heart attacks (myocardial infarction) • bleeding which necessitates a blood transfusion What Actilyse looks like and contents of the pack
this medicine because it contains important • if your thromboplastin time (a blood test to see how lower if you weigh less than 65 kg. It can be • lung-related bleeding, such as blood stained phlegm • vomiting
information for you. The active substance in Actilyse is alteplase. It belongs well your blood clots) is abnormal. This test can be administered in two different ways: (haemoptysis) or bleeding in the respiratory tract • body temperature increased (fever) Actilyse is a powder and solvent for solution for
- Keep this leaflet. You may need to read it again. to a group of medicines called thrombolytic agents. abnormal if you have received heparin (a medicine • bleeding into the membranous sac surrounding the injection and infusion.
- If you have any further questions, ask your doctor or These medicines act by dissolving blood clots that used to “thin” the blood) within the previous a) The 90 minute form of administration, for patients heart (haemopericardium) Death or permanent disability may occur following
nurse. have formed in blood vessels. 48 hours. treated within 6 hours after start of their symptoms. • internal bleeding into the back part of the abdomen bleeding in the brain or other serious bleeding events. Each pack contains one vial with powder and one vial
- If you get any side effects, talk to your doctor or • if you are diabetic and have ever had a stroke before This consists of: (retroperitoneal bleeding) with the solvent.
nurse. This includes any possible side effects not Actilyse 10, 20 or 50 mg are used to treat a number of • if the number of blood platelets (thrombocytes) in • an initial injection of part of the dose of Actilyse into • damage to the heart valves (mitral regurgitation) or Reporting of side effects
listed in this leaflet. See section 4. conditions caused by blood clots forming within blood your blood is very low a vein to the wall dividing the heart chambers (ventricular If you get any side effects, talk to your doctor or nurse. Actilyse is available in the following presentations:
vessels, including: • if you have a very high blood pressure (above • infusions of the remainder of the dose over the septal defect) This includes any possible side effects not listed in this
• heart attack caused by blood clots in the arteries of 185/110) which can only be reduced by injection of following 90 minutes. • bleeding in internal organs, e.g. bleeding in the liver leaflet. You can also report side effects directly (see • One vial of powder with 10 mg alteplase and one vial
the heart (myocardial infarction) medicines (hepatic haemorrhage) details below). By reporting side effects, you can help with 10 ml solvent.
• blood clots in the arteries of the lungs (pulmonary • if the amount of sugar (glucose) in your blood is very b) The 3 hour form of administration, for patients • formation of cholesterol crystal clots which can provide more information on the safety of this • One vial of powder with 20 mg alteplase, one vial
embolism) low (under 50 mg/dl) treated 6 to 12 hours after start of their symptoms. travel to other organs in the body (cholesterol crystal medicine. with 20 ml solvent and one transfer cannula.
• stroke caused by a blood clot in an artery of the brain • if the amount of sugar (glucose) in your blood is very This consists of: embolisation). The symptoms will depend on the • One vial of powder with 50 mg alteplase, one vial
United Kingdom
10 mg, 20 mg and 50 mg
injection and infusion
solvent for solution for
Actilyse® powder and

(acute ischaemic stroke). high (over 400 mg/dl) • an initial injection of part of the dose of Actilyse into organ affected with 50 ml solvent and one transfer cannula.
• if you are under 18 years or over 80 years of age. a vein • allergic reactions, e.g. hives (urticaria) and rash, Yellow Card Scheme
• infusions of the remainder of the dose over the difficulty breathing up to asthma (bronchospasm), Website: www.mhra.gov.uk/yellowcard Not all presentations may be marketed.
2. What you need to know before you receive Actilyse Your doctor will take special care with Actilyse following 3 hours. fluid under the skin and mucose membrane
• if you have had any allergic reaction other than a (angioedema), low blood pressure or shock Ireland Marketing Authorisation Holder
You should not receive Actilyse sudden life-threatening allergic reaction (severe In addition to Actilyse your doctor will give you another • serious allergic reaction (e.g. life-threatening HPRA Pharmacovigilance Boehringer Ingelheim Limited
• if you are allergic (hypersensitive) to the active hypersensitivity) to the active substance alteplase, to medicine to stop the blood clotting. This will be given anaphylaxis) Earlsfort Terrace Ellesfield Avenue
substance alteplase, to gentamicin (a trace residue gentamicin (a trace residue from the manufacturing as soon as possible after your chest pain starts. • heart failure IRL – Dublin 2 Bracknell, Berkshire,
from the manufacturing process), to natural rubber process), to natural rubber (also called latex which is Tel: +353 1 6764971 RG12 8YS, United Kingdom
(also called latex which is part of the packaging part of the packaging material) or to any of the other Blood clots in the arteries of the lungs (pulmonary The following are other possible side effects that may Fax: +353 1 6762517
material) or to any of the other ingredients of this ingredients of this medicine (listed in section 6). embolism) cause your doctor to stop your treatment but, this will Website: www.hpra.ie Manufacturer
medicine (listed in section 6). • if you have or have recently had any other conditions The dose you are given depends on your body weight. depend on how severe the side effects are: e-mail: medsafety@hpra.ie Boehringer Ingelheim Pharma GmbH & Co. KG
• if you have, or have recently had, an illness that that increase your risk of bleeding, such as: The maximum dose of Actilyse is 100 mg but will be Birkendorfer Strasse 65
increases your risk of bleeding, including: - small injury lower if you weigh less than 65 kg. The medicine is Very common (occurs in more than 1 in 10 patients Malta D-88397 Biberach/Riss
- a bleeding disorder or tendency to bleed - biopsy (a procedure for obtaining a tissue usually given as: receiving the medicine) ADR Reporting Germany
- a severe or dangerous bleed in any part of the body specimen) • an initial injection of part of the dose into a vein • fluid on the lungs (pulmonary oedema) The Medicines Authority
10 mg, 20 mg and 50 mg
injection and infusion
solvent for solution for
Actilyse® powder and

- bleeding within the brain or skull - puncture of major vessels • an infusion of the remainder of the dose over the • bleeding of the damaged blood vessel (such as Post-Licensing Directorate
- uncontrolled, very high blood pressure - intramuscular injection following 2 hours. haematoma) 203 Level 3, Rue D‘Argens This leaflet was last revised in 11/2014.
- bacterial infection or inflammation of the heart - external heart massage • low blood pressure (hypotension) GŻR-1368 Gżira
(endocarditis), or inflammation of the membranes • if you have ever received Actilyse before. After the treatment with Actilyse, your doctor will start • chest pain (angina pectoris) Website: www.medicinesauthority.gov.mt
around the heart (pericarditis) • if you are over 65 years of age. (or resume) therapy with heparin (a medicine to “thin” e-mail: postlicensing.medicinesauthority@gov.mt
- inflammation of the pancreas (acute pancreatitis) the blood). Common (occurs in less than 1 in 10 patients receiving
- gastric ulcer or ulcers in the gut Other medicines and Actilyse the medicine)
- varicose veins in the gullet (oesophageal varices) Please tell your doctor if you are taking or have recently Stroke caused by a blood clot in an artery of the brain • further heart attack 5. How to store Actilyse
- abnormalities of the blood vessels, such as a taken any other medicines, including medicines (acute ischaemic stroke) • bleeding in the throat
localised swelling of an artery (aneurysm) obtained without a prescription. It is particularly Actilyse must be given within 4.5 hours of the first • bleeding in the stomach or gut, including vomiting Normally you will not be asked to store Actilyse as it
- certain tumours important that you tell your doctor if you are taking or symptoms. The earlier you receive Actilyse, the more blood (haematemesis) or blood in the stools will be given to you by your doctor.
- severe liver disease have recently taken: you can benefit from the treatment and the less likely (melanea or rectal haemorrhage), bleeding of the
• if you are taking a medicine used to “thin” the blood • any medicines which are used to “thin” the blood, are harmful side effects to occur. The dose you are gums Keep out this medicine of the sight and reach of
(oral anticoagulants), unless appropriate tests including: given depends on your body weight. The maximum • bleeding into the body tissues causing purplish children.
What is in this leaflet: confirmed no clinically relevant activity of such - acetylsalicylic acid dose of this medicine is 90 mg but will be lower if you bruising (ecchymosis)
1. What Actilyse is and what it is used for medicine - warfarin weigh less than 100 kg. Actilyse is given as: • bleeding from the urinary tract or the reproductive Do not store above 25°C. Store in the original package
2. What you need to know before you receive Actilyse • if you have ever had surgery to your brain or spine - coumarin • an initial injection of part of the dose into a vein organs, which may lead to blood in your urine in order to protect from light.
3. How is Actilyse administered • if you have had major surgery or significant injury in - heparin • an infusion of the remainder of the dose over the (haematuria)
4. Possible side effects the past 3 months • certain medicines used to treat high blood pressure following 60 minutes. • bleeding or bruising (haematoma) where the Actilyse should not be used after the expiry date which
5. How to store Actilyse • if you had a recent puncture of a major blood vessel (ACE inhibitors). injection is given is stated on the vial label and the carton. The expiry
6. Contents of the pack and other information • if you have been given external heart massage in the You should not take acetylsalicylic acid for the first date refers to the last day of that month.
past 10 days Pregnancy, breast-feeding and fertility 24 hours after your treatment with Actilyse for a stroke. Uncommon (occurs in less than 1 in 100 patients
• if you have had a baby in the past 10 days Ask your doctor for advice before taking any medicine. Your doctor may give you an injection with heparin if receiving the medicine) After reconstitution: From a microbiological point of
Your doctor will only give you Actilyse if the possible this is necessary. • nosebleeds (epistaxis) view, the product should be used immediately after
Your doctor will also not use Actilyse for the treatment benefit outweighs the possible risk to your baby. • irregular heart beat after the blood supply to the reconstitution. If not used immediately, in-use storage
of heart attacks or blood clots in the arteries of the If you have any further questions on the use of heart has been restored times and conditions prior to use are the responsibility
lungs Actilyse may contain gentamicin as trace residue from Actilyse, ask your doctor or health care professional. • Sudden blocking of an artery in the lungs (pulmonary of the user and would normally not be longer than
• if you have or have ever had a stroke caused by the manufacturing process; the packaging contains embolsim), the brain (cerebral embolism) and all 24 hours at 2 – 8°C.
bleeding in the brain (haemorrhagic stroke) natural rubber (latex). other areas of the body (systemic embolism)
• if you have or have ever had a stroke of unknown • bleeding from the ear
cause • blood pressure decreased
• if you have recently (in the past 6 months) had a
stroke caused by a blood clot in an artery of the brain Rare (occurs in less than 1 in 1,000 patients receiving
(ischaemic stroke), unless this is the stroke you are the medicine)
about to be treated for • formation of blood clots in the blood vessels which
can travel to other organs in the body (embolism).
The symptoms will depend on the organ affected.
• bleeding in the eyes (eye haemorrhage)
• uneasiness of the stomach (nausea)

B
Mandatory in
File information TD Printfile
Issue date of TD: 15.04.2014 Yes Yes
PPM SKU: P010161 No Yes A
PPM SKU version:  004 No Yes
Issue date of artwork: 14.11.2014 No Yes
Print colors: PAN Black No Yes D

Mat. No. Pack. Site: 307453-01 No Yes Mass A 25,5 mm

Min. font size: 10pt Mass B 2,2 mm
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Additional Requirements of Packaging site

Template name: TD-PI_630x350 Index: e
The following information is intended for healthcare Posology and method of administration Pulmonary embolism
professionals only:
Acute Myocardial infarction Posology
2 mg vials of alteplase are not indicated for use in the A total dose of 100 mg of alteplase should be
indications myocardial infarction, pulmonary Posology administered in 2 hours. Most experience is available
embolism or acute ischaemic stroke (due to risk of a) 90 minutes (accelerated) dose regimen for patients with the following dose regimen:
massive under dosing). Only 10, 20 or 50 mg vials are with myocardial infarction, in whom treatment can
indicated for use in these indications. be started within 6 hours after symptom onset: Concentration of alteplase
1 mg/ml 2 mg/ml
Reconstitution Concentration of alteplase ml ml
1 mg/ml 2 mg/ml 10 mg as an intravenous
For reconstitution to a final concentration of 1 mg ml ml 10 5
bolus over 1 - 2 minutes
alteplase per ml the full volume of solvent provided 15 mg as an
should be transferred to the vial containing the Actilyse 15 7.5 followed by an
intravenous bolus
powder. To this purpose a transfer cannula is included intravenous infusion 90 45
with the 20 mg and 50 mg presentations, which is to 50 mg as an infusion of 90 mg over 2 hours
over 30 minutes 50 25
be used. For the 10 mg vial a syringe should be used.
followed by an infusion The total dose should not exceed 1.5 mg/kg in patients
For reconstitution to a final concentration of 2 mg of 35 mg over 60 minutes with a body weight below 65 kg.
alteplase per ml only half of the solvent provided 35 17.5
until the maximal dose
should be used (as per table below). In these cases of 100 mg Adjunctive therapy: After treatment with Actilyse
always a syringe should be used to transfer the heparin therapy should be initiated (or resumed) when
required amount of solvent to the vial containing the aPTT values are less than twice the upper limit of
Actilyse powder. In patients with a body weight below 65 kg the dose normal. The infusion should be adjusted to maintain
should be weight adjusted according to the following aPTT between 50 - 70 seconds (1.5 to 2.5 fold of the
Under aseptic conditions the content of an injection table: reference value).
vial of Actilyse (10 mg or 20 mg or 50 mg) is dissolved
with water for injections according to the following Concentration of alteplase Method of administration
table to obtain either a final concentration of 1 mg 1 mg/ml 2 mg/ml The reconstituted solution should be administered
alteplase/ml or 2 mg alteplase/ml: ml ml intravenously.
15 mg as an 2 mg vials of alteplase are not indicated for use in this
Actilyse vial 10 mg 20 mg 50 mg 15 7.5
intravenous bolus indication.
Volume of water for ml/kg bw ml/kg bw

injections to be added Acute ischaemic stroke
and 0.75 mg/kg body
to dry powder (ml):
weight (bw) over
30 minutes 0.75 0.375 Treatment must only be performed under the
Final concentration (maximum 50 mg) responsibility and follow-up of a physician trained and
(a) 1 mg alteplase/ml 10 20 50 experienced in neurovascular care, see SmPC sections
followed by an infusion 4.3 contraindications and 4.4 special warnings/
(b) 2 mg alteplase/ml of 0.5 mg/kg body precautions for use.
5 10 25
weight (bw) over 60 0.5 0.25
minutes (maximum Posology
The reconstituted solution should then be 35 mg) The recommended dose is 0.9 mg alteplase/kg body
administered intravenously. It may be diluted further weight (maximum of 90 mg) infused intravenously over
with sterile sodium chloride 9 mg/ml (0.9 %) solution 60 minutes with 10% of the total dose administered as
for injection up to a minimal concentration of b) 3 h dose regimen for patients, in whom treatment an initial intravenous bolus.
0.2 mg/ml. A dilution of the reconstituted solution can be started between 6 and 12 hours after
with sterilised water for injections or in general, the symptom onset: Treatment with Actilyse must be started as early as
use of carbohydrate infusion solutions, e.g. dextrose is possible within 4.5 hours of the onset of symptoms.
not recommended. Actilyse should not be mixed with Concentration of alteplase Beyond 4.5 hours after onset of stroke symptoms
other medicinal products in the same infusion-vial (not 1 mg/ml 2 mg/ml there is a negative benefit risk ratio associated with
even with heparin). ml ml Actilyse administration and so it should not be
10 mg as an administered (see SmPC section 5.1).
When reconstituting the product from the respective 10 5
intravenous bolus
amount of powder and solvent, the mixture should Adjunctive therapy: The safety and efficacy of this
only be agitated gently until complete dissolution. Any 50 mg as an infusion 50 25 regimen with concomitant administration of heparin
vigorous agitation should be avoided to prevent foam over the first hour and acetylsalicylic acid within the first 24 hours of
formation. ml/30 min ml/30 min onset of the symptoms have not been sufficiently
investigated. Administration of acetylsalicylic acid or
The reconstituted preparation is a clear and colourless followed by infusions of intravenous heparin should be avoided in the first
to pale yellow solution. Prior to administration it 10 mg over 30 minutes 24 hours after treatment with Actilyse. If heparin is
until the maximal dose 10 5
should be inspected visually for particles and colour. required for other indications (e.g. prevention of deep
of 100 mg over 3 hours vein thrombosis) the dose should not exceed 10,000 IU
For storage conditions, please see section 5 of this per day, administered subcutaneously.
leaflet. In patients with a body weight below 65 kg the total
dose should not exceed 1.5 mg/kg. Method of administration
The reconstituted solution is for single use only. Any The reconstituted solution should be administered
unused solution should be discarded. The maximum dose of alteplase is 100 mg. intravenously.

Adjunctive therapy: Antithrombotic adjunctive therapy 2 mg vials of alteplase are not indicated for use in this
is recommended according to the current international indication.
guidelines for the management of patients with
ST-elevation myocardial infarction; Paediatric population
The safety and efficacy of Actilyse in children and
Method of administration adolescents has not yet been established. Actilyse is
The reconstituted solution should be administered contraindicated for the treatment of acute stroke in
intravenously. children and adolescents (see SmPC section 4.3).

2 mg vials of alteplase are not indicated for use in this

indication.