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ACTILYSE 50 MG POWDER AND SOLVENT FOR SOLUTION FOR INJECTION AND INFUSION

Active substance(s): ALTEPLASE / WATER FOR INJECTIONS

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Package leaflet: Information for the user

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

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
1. What Actilyse is and what it is used for
started

• if your thromboplastin time (a blood test to see how
The active substance in Actilyse is alteplase. It belongs
well your blood clots) is abnormal. This test can be
to a group of medicines called thrombolytic agents.
abnormal if you have received heparin (a medicine
These medicines act by dissolving blood clots that
used to “thin” the blood) within the previous
have formed in blood vessels.
48 hours.
• if you are diabetic and have ever had a stroke before
Actilyse 10, 20 or 50 mg are used to treat a number of
• if the number of blood platelets (thrombocytes) in
conditions caused by blood clots forming within blood
your blood is very low
vessels, including:
• if you have a very high blood pressure (above
• heart attack caused by blood clots in the arteries of
185/110) which can only be reduced by injection of
the heart (myocardial infarction)
medicines
• blood clots in the arteries of the lungs (pulmonary
• if the amount of sugar (glucose) in your blood is very
embolism)
low (under 50 mg/dl)
• stroke caused by a blood clot in an artery of the brain • if the amount of sugar (glucose) in your blood is very
(acute ischaemic stroke).
high (over 400 mg/dl)

• if you are under 18 years or over 80 years of age.


2. What you need to know before you receive Actilyse
Your doctor will take special care with Actilyse

• if you have had any allergic reaction other than a
You should not receive Actilyse
sudden life-threatening allergic reaction (severe
• if you are allergic (hypersensitive) to the active
hypersensitivity) to the active substance alteplase, to
substance alteplase, to gentamicin (a trace residue
gentamicin (a trace residue from the manufacturing
from the manufacturing process), to natural rubber
process), to natural rubber (also called latex which is
(also called latex which is part of the packaging
part of the packaging material) or to any of the other
material) or to any of the other ingredients of this
ingredients of this medicine (listed in section 6).
medicine (listed in section 6).
• if you have or have recently had any other conditions
• if you have, or have recently had, an illness that
that increase your risk of bleeding, such as:
increases your risk of bleeding, including:
- small injury
- a bleeding disorder or tendency to bleed
- biopsy (a procedure for obtaining a tissue
- a severe or dangerous bleed in any part of the body
specimen)
- bleeding within the brain or skull
- puncture of major vessels
- uncontrolled, very high blood pressure
- intramuscular injection
- bacterial infection or inflammation of the heart
- external heart massage
(endocarditis), or inflammation of the membranes
• if you have ever received Actilyse before.
around the heart (pericarditis)
• if you are over 65 years of age.
- inflammation of the pancreas (acute pancreatitis)

- gastric ulcer or ulcers in the gut
Other medicines and Actilyse
- varicose veins in the gullet (oesophageal varices)
Please tell your doctor if you are taking or have recently
- abnormalities of the blood vessels, such as a
taken any other medicines, including medicines
localised swelling of an artery (aneurysm)
obtained without a prescription. It is particularly
- certain tumours
important that you tell your doctor if you are taking or
- severe liver disease
have recently taken:
• if you are taking a medicine used to “thin” the blood • any medicines which are used to “thin” the blood,
(oral anticoagulants), unless appropriate tests
including:
confirmed no clinically relevant activity of such
- acetylsalicylic acid
medicine
- warfarin
• if you have ever had surgery to your brain or spine
- coumarin
• if you have had major surgery or significant injury in - heparin
the past 3 months
• certain medicines used to treat high blood pressure
(ACE inhibitors).
• if you had a recent puncture of a major blood vessel
• if you have been given external heart massage in the
past 10 days
Pregnancy, breast-feeding and fertility
Ask your doctor for advice before taking any medicine.
• if you have had a baby in the past 10 days
Your doctor will only give you Actilyse if the possible

benefit outweighs the possible risk to your baby.
Your doctor will also not use Actilyse for the treatment
of heart attacks or blood clots in the arteries of the

lungs
Actilyse may contain gentamicin as trace residue from
the manufacturing process; the packaging contains
• if you have or have ever had a stroke caused by
natural rubber (latex).
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


abcd



Alteplase
Read all of this leaflet carefully before you start using
this medicine because it contains important
information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor or
nurse.
- If you get any side effects, talk to your doctor or
nurse. This includes any possible side effects not
listed in this leaflet. See section 4.

Actilyse® powder and
solvent for solution for
injection and infusion
10 mg, 20 mg and 50 mg
Actilyse® powder and
solvent for solution for
injection and infusion
10 mg, 20 mg and 50 mg
What is in this leaflet:
1. What Actilyse is and what it is used for
2. What you need to know before you receive Actilyse
3. How is Actilyse administered
4. Possible side effects
5. How to store Actilyse
6. Contents of the pack and other information

B

Mandatory in

File information

TD

Printfile

Issue date of TD:

15.04.2014

Yes

Yes

PPM SKU:

P010161

No

Yes

PPM SKU version: 

004

No

Yes

Issue date of artwork:

14.11.2014

No

Yes

Print colors:

PAN Black

No

Yes

A

D
C

Mat. No. Pack. Site:

307453-01

Min. font size:

10pt

Legend case version:

V4.0 01/OCT/2012 (please do not change or remove it)

No

Technical information
a = Batch No.

b = Expiry date

c = Manufacturing date

d = Price/Sample/Clinic

Technical colors
BI-Diecut-Legendcase

Free area

Gluepoints

Additional Requirements of Packaging site
Template name: TD-PI_630x350

Index: e

Yes

Mass
Mass
Mass
MASS

A
B
C
D

25,5 mm
2,2 mm
max. 48 mm
3 mm

3. How is Actilyse administered

Actilyse will be prepared and 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 acetylsalicylic acid 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.

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




4. Possible side effects

Very rare (occurs in less than 1 in 10,000 patients
receiving the medicine)
Like all medicines, Actilyse can cause side effects,
• events which affect the nervous system such as:
although not everybody gets them. The side effects
- cramps (convulsions, fits)
described below have been experienced by people
- speech problems
given Actilyse. Your treatment may be stopped by your
- confusion or delirium (very severe confusion)
doctor if any of the following side effects occur:
- anxiety accompanied by restlessness (agitation)
- depression
• bleeding in the brain (cerebral haemorrhage) after
- altered thinking (psychosis)
the treatment of a stroke caused by a blood clot in an These disorders often occur in association with a
artery of the brain (acute ischaemic stroke)
stroke caused by a blood clot or bleeding in the brain.
• cessation of heartbeat (cardiac arrest)
• shock (a very low blood pressure) due to heart failure Not known (frequency cannot be estimated from
• bleeding in the brain (cerebral haemorrhage) after
available data)
the treatment of heart attacks (myocardial infarction) • bleeding which necessitates a blood transfusion
• lung-related bleeding, such as blood stained phlegm • vomiting
(haemoptysis) or bleeding in the respiratory tract
• body temperature increased (fever)
• bleeding into the membranous sac surrounding the

heart (haemopericardium)
Death or permanent disability may occur following
• internal bleeding into the back part of the abdomen bleeding in the brain or other serious bleeding events.
(retroperitoneal bleeding)

• damage to the heart valves (mitral regurgitation) or
Reporting of side effects
to the wall dividing the heart chambers (ventricular
If you get any side effects, talk to your doctor or nurse.
septal defect)
This includes any possible side effects not listed in this
• bleeding in internal organs, e.g. bleeding in the liver leaflet. You can also report side effects directly (see
(hepatic haemorrhage)
details below). By reporting side effects, you can help
• formation of cholesterol crystal clots which can
provide more information on the safety of this
travel to other organs in the body (cholesterol crystal medicine.
embolisation). The symptoms will depend on the
organ affected
United Kingdom
• allergic reactions, e.g. hives (urticaria) and rash,
Yellow Card Scheme
difficulty breathing up to asthma (bronchospasm),
Website: www.mhra.gov.uk/yellowcard
fluid under the skin and mucose membrane
(angioedema), low blood pressure or shock
Ireland
• serious allergic reaction (e.g. life-threatening
HPRA Pharmacovigilance
anaphylaxis)
Earlsfort Terrace
• heart failure
IRL – Dublin 2
Tel: +353 1 6764971
The following are other possible side effects that may
Fax: +353 1 6762517
cause your doctor to stop your treatment but, this will
Website: www.hpra.ie
depend on how severe the side effects are:
e-mail: medsafety@hpra.ie
Very common (occurs in more than 1 in 10 patients
receiving the medicine)
• fluid on the lungs (pulmonary oedema)
• bleeding of the damaged blood vessel (such as
haematoma)
• low blood pressure (hypotension)
• chest pain (angina pectoris)
Common (occurs in less than 1 in 10 patients receiving
the medicine)
• further heart attack
• bleeding in the throat
• bleeding in the stomach or gut, including vomiting
blood (haematemesis) or blood in the stools
(melanea or rectal haemorrhage), bleeding of the
gums
• 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 or bruising (haematoma) where the
injection is given

Malta
ADR Reporting
The Medicines Authority
Post-Licensing Directorate
203 Level 3, Rue D‘Argens
GŻR-1368 Gżira
Website: www.medicinesauthority.gov.mt
e-mail: postlicensing.medicinesauthority@gov.mt


5. How to store Actilyse

Normally you will not be asked to store Actilyse as it
will be given to you by your doctor.

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

Do not store above 25°C. Store in the original package
in order to protect from light.

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.
Uncommon (occurs in less than 1 in 100 patients

receiving the medicine)
After reconstitution: From a microbiological point of
• nosebleeds (epistaxis)
view, the product should be used immediately after
• irregular heart beat after the blood supply to the
reconstitution. If not used immediately, in-use storage
times and conditions prior to use are the responsibility
heart has been restored
• Sudden blocking of an artery in the lungs (pulmonary of the user and would normally not be longer than
embolsim), the brain (cerebral embolism) and all
24 hours at 2 – 8°C.
other areas of the body (systemic embolism)

• bleeding from the ear

• blood pressure decreased
Rare (occurs in less than 1 in 1,000 patients receiving
the medicine)
• 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)

6. Contents of the pack and other information

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. 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.
Each pack contains one vial with powder and one vial
with the solvent.
Actilyse is available in the following presentations:
• 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 presentations may be marketed.

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 revised in 11/2014.



The following information is intended for healthcare
professionals only:
2 mg vials of alteplase are not indicated for use in the
indications myocardial infarction, pulmonary
embolism or acute ischaemic stroke (due to risk of
massive under dosing). Only 10, 20 or 50 mg vials are
indicated for use in these indications.
Reconstitution
For reconstitution to a final concentration of 1 mg
alteplase per ml the full volume of solvent provided
should be transferred to the vial containing the Actilyse
powder. To this purpose a transfer cannula is included
with the 20 mg and 50 mg presentations, which is to
be used. For the 10 mg vial a syringe should be used.
For reconstitution to a final concentration of 2 mg
alteplase per ml only half of the solvent provided
should be used (as per table below). In these cases
always a syringe should be used to transfer the
required amount of solvent to the vial containing the
Actilyse powder.
Under aseptic conditions the content of an injection
vial of Actilyse (10 mg or 20 mg or 50 mg) is dissolved
with water for injections according to the following
table to obtain either a final concentration of 1 mg
alteplase/ml or 2 mg alteplase/ml:
Actilyse

vial






10 mg

20 mg

50 mg

Volume of water for
injections to be added
to dry powder (ml):

Final concentration
(a) 1 mg alteplase/ml

10

20

50

(b) 2 mg alteplase/ml

5

10

25

The reconstituted solution should then be
administered intravenously. It may be diluted further
with sterile sodium chloride 9 mg/ml (0.9 %) solution
for injection up to a minimal concentration of
0.2 mg/ml. A dilution of the reconstituted solution
with sterilised water for injections or in general, the
use of carbohydrate infusion solutions, e.g. dextrose is
not recommended. Actilyse should not be mixed with
other medicinal products in the same infusion-vial (not
even with heparin).

Posology and method of administration

Pulmonary embolism

Acute Myocardial infarction

Posology
A total dose of 100 mg of alteplase should be
administered in 2 hours. Most experience is available
with the following dose regimen:

Posology
a) 90 minutes (accelerated) dose regimen for patients
with myocardial infarction, in whom treatment can
be started within 6 hours after symptom onset:
Concentration of alteplase
1 mg/ml
2 mg/ml
ml
ml


15 mg as an
intravenous bolus

15

50 mg as an infusion
over 30 minutes

50

followed by an infusion
of 35 mg over 60 minutes
until the maximal dose
of 100 mg

35

7.5
25
17.5

In patients with a body weight below 65 kg the dose
should be weight adjusted according to the following
table:


Concentration of alteplase
1 mg/ml
2 mg/ml
ml
ml

15 mg as an
intravenous bolus

15

7.5

ml/kg bw

ml/kg bw

0.75

0.375

followed by an infusion
of 0.5 mg/kg body
weight (bw) over 60
minutes (maximum
35 mg)

0.5

0.25

b) 3 h dose regimen for patients, in whom treatment
can be started between 6 and 12 hours after
symptom onset:
Concentration of alteplase
1 mg/ml
2 mg/ml
ml
ml
10 mg as an
intravenous bolus

10

5

50 mg as an infusion
over the first hour

50

25

The reconstituted preparation is a clear and colourless
to pale yellow solution. Prior to administration it
should be inspected visually for particles and colour.

followed by infusions of
10 mg over 30 minutes
until the maximal dose
of 100 mg over 3 hours

The reconstituted solution is for single use only. Any
unused solution should be discarded.


10 mg as an intravenous
bolus over 1 - 2 minutes

10

5

followed by an
intravenous infusion
of 90 mg over 2 hours

90

45

The total dose should not exceed 1.5 mg/kg in patients
with a body weight below 65 kg.
Adjunctive therapy: After treatment with Actilyse
heparin therapy should be initiated (or resumed) when
aPTT values are less than twice the upper limit of
normal. The infusion should be adjusted to maintain
aPTT between 50 - 70 seconds (1.5 to 2.5 fold of the
reference value).
Method of administration
The reconstituted solution should be administered
intravenously.
2 mg vials of alteplase are not indicated for use in this
indication.
Acute ischaemic stroke

and 0.75 mg/kg body
weight (bw) over
30 minutes
(maximum 50 mg)

When reconstituting the product from the respective
amount of powder and solvent, the mixture should
only be agitated gently until complete dissolution. Any
vigorous agitation should be avoided to prevent foam
formation.

For storage conditions, please see section 5 of this
leaflet.

Concentration of alteplase
1 mg/ml
2 mg/ml
ml
ml

ml/30 min

ml/30 min

10

5

In patients with a body weight below 65 kg the total
dose should not exceed 1.5 mg/kg.
The maximum dose of alteplase is 100 mg.
Adjunctive therapy: Antithrombotic adjunctive therapy
is recommended according to the current international
guidelines for the management of patients with
ST-elevation myocardial infarction;
Method of administration
The reconstituted solution should be administered
intravenously.
2 mg vials of alteplase are not indicated for use in this
indication.

Treatment must only be performed under the
responsibility and follow-up of a physician trained and
experienced in neurovascular care, see SmPC sections
4.3 contraindications and 4.4 special warnings/
precautions for use.
Posology
The recommended dose is 0.9 mg alteplase/kg body
weight (maximum of 90 mg) infused intravenously over
60 minutes with 10% of the total dose administered as
an initial intravenous bolus.
Treatment with Actilyse must be started as early as
possible within 4.5 hours of the onset of symptoms.
Beyond 4.5 hours after onset of stroke symptoms
there is a negative benefit risk ratio associated with
Actilyse administration and so it should not be
administered (see SmPC section 5.1).
Adjunctive therapy: The safety and efficacy of this
regimen with concomitant administration of heparin
and acetylsalicylic acid within the first 24 hours of
onset of the symptoms have not been sufficiently
investigated. Administration of acetylsalicylic acid or
intravenous heparin should be avoided in the first
24 hours after treatment with Actilyse. If heparin is
required for other indications (e.g. prevention of deep
vein thrombosis) the dose should not exceed 10,000 IU
per day, administered subcutaneously.
Method of administration
The reconstituted solution should be administered
intravenously.
2 mg vials of alteplase are not indicated for use in this
indication.
Paediatric population
The safety and efficacy of Actilyse in children and
adolescents has not yet been established. Actilyse is
contraindicated for the treatment of acute stroke in
children and adolescents (see SmPC section 4.3).

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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