Actilyse 50 mg powder and solvent for solution for injection and infusion, Actilyse 20 mg powder and solvent for solution for injection and infusion, Actilyse 10 mg powder and solvent for solution for injection and infusion – patient leaflet, side effects, dosage

1. What Actilyse is and what it is used for

start

again. r

ctor

ffects

2. What you need to know before you rece

Actilyse

1. 3. How is Actilyse administered
2. 4. Possible side effects
3. 5. How to store Actilyse
4. 6. Contents of the pack and other informa
5. 1. What Actilyse is and what it is used for

The active substance in Actilyse is alteplase It belongs to a group of medicines called thrombolytic agents. These medicines act b dissolving blood clots that have formed in vessels.

ive

tion

.

y

blood

Actilyse 10, 20 or 50 mg are used to treat a number of conditions caused by blood cl forming within blood vessels, including:

• heart attack caused by blood clots in the a of the heart (acute myocardial infarction)
• blood clots in the arteries of the lungs (acute massive pulmonary embolism)
• stroke caused by a blood clot in an artery brain (acute ischaemic stroke).
• What you need to know before you rece Actilyse

You should not receive Actilyse

ots

rteries

of the

ive

• if you are allergic (hypersensitive) to the a substance alteplase, to gentamicin (a trace residue from the manufacturing process) o any of the other ingredients of this medici (listed in section 6).

• if you have, or have recently had, an illne increases your risk of bleeding, including:

  • a bleeding disorder or tendency to bleed

  • a severe or dangerous bleed in any part

    body

  • bleeding within the brain or skull
  • uncontrolled, very high blood pressure

  • bacterial infection or inflammation of th

    heart (endocarditis), or inflammation of membranes around the heart (pericardit

  • inflammation of the pancreas (acute

    ctive

    r to

    ne

    ss that

    of the

    e

    the

    is)

    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 sig injury in the past 3 months
  • if you had a recent puncture of a m vessel
  • if you have been given external hea in the past 10 days
  • if you have had a baby in the past 1

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

• if you have or have ever had a strok

  nificant

  ajor blood

  rt massage

  0 days

  for the

  ots in the

  e caused by

  bleeding in the brain (haemorrhagi

• if you have or have ever had a strok unknown cause
• if you have recently (in the past 6 m a stroke caused by a blood clot in a the brain (ischaemic stroke), unless stroke you are about to be treated f

In addition your doctor will not use A the treatment of a stroke caused by a in an artery of the brain (acute ischae

• if the symptoms of your stroke beg than 4.5 hours ago or if it may be p the symptoms began more than 4. because you do not know when the

  c stroke)

  e of

  onths) had n artery of this is the or

  ctilyse for blood clot mic stroke) an more

  ossible that 5 hours ago, y began

• if your stroke is causing only very mi
• if there are signs of bleeding in the
• if you have had a stroke within the months
• if the symptoms are rapidly improv receiving Actilyse
• if you have a very severe stroke
• if you had cramps (convulsions) wh stroke started
• if your thromboplastin time (a bloo how well your blood clots) is abnor test can be abnormal if you have re heparin (a medicine used to “thin” within the previous 48 hours.

• if you are diabetic and have ever ha

  ld symptoms brain

  last three

  ing before

  en your

  d test to see mal. This

  ceived

  the blood)

  d a stroke

  before

• if the number of blood platelets (th in your blood is very low
• if you have a very high blood press 185/110) which can only be reduce injection of medicines
• if the amount of sugar (glucose) in is very low (under 50 mg/dl)
• if the amount of sugar (glucose) in is very high (over 400 mg/dl)
• if you are under 16 years of age. (For of 16 years of age or older see sectio doctor will take special care with Ac

Your doctor will take special care wit

rombocytes)

ure (above d by

your blood

your blood

adolescents n “Your

tilyse”.)

h 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) 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
    • external heart massage
  • if you have ever received Actilyse before.
  • if you are over 65 years of ag
  • if you are over 80 years of ag a poorer outcome regardless Actilyse. However, in general Actilyse in patients over 80 y and age alone is not a barrier Actilyse.
  • if you are an adolescent of 16 older the benefit will be weig against the risks on an indivi treatment of acute ischaemic

Other medicines and Actilyse

Please tell your doctor if you ar recently taken any other medic medicines obtained without a

e.

e, you may have of treatment with the benefit-risk of ears is positive to treatment with

years of age or hed carefully

dual basis for the stroke.

e taking or have ines, including prescription. It is

particularly important that you you are taking or have recently

• any medicines which are use blood, including:

  • acetylsalicylic acid
  • warfarin
  • coumarin
  • heparin
• certain medicines used to tre pressure (ACE inhibitors).

Pregnancy, breast-feeding and

Ask your doctor for advice befo medicine. Your doctor will only if the possible benefit outweig

tell your doctor if taken:

d to “thin” the

at high blood

fertility

re taking any

give you Actilyse hs the possible

risk to your baby.

Actilyse may contain gentamic from the manufacturing proce

3. How is Actilyse administere

Actilyse will be prepared and a you by your doctor or by a heal professional. It is not for self-a

Treatment with Actilyse should soon as possible after the start

There are three different condit

in as trace residue ss.

d

dministered to th care

dministration.

be initiated as of your symptoms.

ions for which

this medicine can be given:

Heart attack (acute myocardial

The dose you are given depend weight. The maximum dose of but will be lower if you weigh le It can be administered in two d

1. a) The 90 minute form of admi patients treated within 6 hou their symptoms. This consist
2. • an initial injection of part of Actilyse into a vein
3. •

   infusions of the remainder of following 90 minutes.

   infarction)

   s on your body Actilyse is 100 mg ss than 65 kg. ifferent ways:

   nistration, for

   rs after start of s of:

   the dose of

   the dose over the

4. b)

   The 3 hour form of administration, for patients

   treated 6 to 12 hours after start of their symptoms. This consists of:

5. • an initial injection of part of the dose of Actilyse into a vein
6. • 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 (acute massive 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 start (or resume) therapy (a medicine to “thin” the

Stroke caused by a blood brain (acute ischaemic st

Actilyse must be given w first symptoms. The earli the more you can benefit the less likely are harmfu The dose you are given d weight. The maximum do 90 mg but will be lower if 100 kg. Actilyse is given

• an initial injection of pa

• an infusion of the rema

  Actilyse, your doctor will with heparin

  blood).

  clot in an artery of the roke)

  ithin 4.5 hours of the er you receive Actilyse, from the treatment and l side effects to occur. epends on your body se of this medicine is you weigh less than as:

  rt of the dose into a vein inder of the dose over

  the following 60 minut

You should not take acet first 24 hours after your t for a stroke. Your doctor injection with heparin if

If you have any further q Actilyse, ask your doctor professional.

4. Possible side effects

Like all medicines, this m

es.

ylsalicylic acid for the reatment with Actilyse may give you an

this is necessary.

uestions on the use of or health care

edicine can cause side

effects, although not eve side effects described be experienced by people gi

Your treatment may be st any of the following side

Very common (occurs in patients receiving the me

• heart failure
• bleeding in the brain (c after the treatment of a a blood clot in an arter ischaemic stroke)

Common (occurs in less

rybody gets them. The low have been

ven Actilyse.

opped by your doctor if effects occur:

more than 1 in 10 dicine)

erebral haemorrhage) stroke caused by y of the brain (acute

than 1 in 10 patients

receiving the medicine)

• bleeding in the brain (c after the treatment of h infarction)
• cessation of heartbeat
• shock (a very low blood failure

Uncommon (occurs in le receiving the medicine)

• lung-related bleeding, phlegm (haemoptysis) respiratory tract

• damage to the heart val or to the wall dividing t (ventricular septal defe

  erebral haemorrhage) eart attacks (myocardial

  (cardiac arrest)

  pressure) due to heart

  ss than 1 in 100 patients

  such as blood stained or bleeding in the

  ves (mitral regurgitation) he heart chambers

  ct)

Rare (occurs in less than 1 in 1,000 patients receiving the medicine)

• bleeding into the membranous sac surrounding the heart (haemopericardium)
• internal bleeding into the back part of the abdomen (retroperitoneal bleeding)

• allergic reactions, e.g. hives (urticaria) and rash, difficulty breathing up to asthma (bronchospasm), fluid under the skin and mucose membrane (angioedema), low blood pressure or shock

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

  • serious allergic reaction (e.g. life-threatening anaphylaxis)

Not known (frequency cannot be estimated from available data)

• bleeding in internal organs, e.g. bleeding in the liver (hepatic haemorrhage)

• formation of cholesterol crystal clots which

  can travel to oth (cholesterol cryst symptoms will d

The following are o may cause your doc this will depend on

Very common (occ 10 patients receivi

• fluid on the lung
• bleeding of the d haematoma)
• low blood pressu

• chest pain (angin

  er organs in the body

  al embolisation). The

  epend on the organ affected

  ther possible side effects that tor to stop your treatment but, how severe the side effects are:

  urs in more than 1 in

  ng the medicine)

  s (pulmonary oedema)

  amaged blood vessel (such as

  re (hypotension)

  a pectoris)

Common (occurs i receiving the medi

• further heart atta
• bleeding in the t
• bleeding in the s vomiting blood ( stools (melanea bleeding of the g
• bleeding into the bruising (ecchym
• bleeding from th reproductive org in your urine (ha

• bleeding or bruis injection is given

  n less than 1 in 10 patients cine)

  ck

  hroat

  tomach or gut, including haematemesis) or blood in the or rectal haemorrhage), ums

  body tissues causing purplish osis)

  e urinary tract or the

  ans, which may lead to blood ematuria)

  ing (haematoma) where the

Uncommon (occur receiving the medi

• nosebleeds (epis
• irregular heart be the heart has bee
• sudden blocking (pulmonary emb embolism) and a (systemic emboli
• bleeding from th
• blood pressure d

Rare (occurs in les receiving the medi

• formation of blo

  s in less than 1 in 100 patients cine)

  taxis)

  at after the blood supply to n restored

  of an artery in the lungs olism), the brain (cerebral ll other areas of the body sm)

  e ear

  ecreased

  s than 1 in 1,000 patients cine)

  od clots in the blood vessels

  which can travel (embolism). The organ affected.

• bleeding in the e
• uneasiness of th

Very rare (occurs in receiving the medi

• events which affe

  • cramps (convul
  • speech problem
  • confusion or de

  • anxiety accomp

    (agitation)

  • depression

    to other organs in the body symptoms will depend on the

    yes (eye haemorrhage)

    e stomach (nausea)

    less than 1 in 10,000 patients cine)

    ct the nervous system such as: sions, fits)

    s

    lirium (very severe confusion) anied by restlessness

  • altered thinking (psychosis)

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

Not known (frequency cannot be estimated from available data)

• bleeding which necessitates a blood transfusion
• vomiting

• body temperature increased (fever)

  Death or permanent disability may occur following bleeding in the brain or other serious bleeding events.

  Reporting of side effects

  If you get 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 (see details below). By reporting side effects, you can help provide more information

  Yellow Card Website: ww for MHRA Ye Apple App S

5. How to st

Normally yo as it will be g

Keep this me children.

on the safety of this medicine.

Scheme

w.mhra.gov.uk/yellowcard or search llow Card in the Google Play or tore

ore Actilyse

u will not be asked to store Actilyse iven to you by your doctor.

dicine out of the sight and reach of

Do not store package in o

Actilyse sho which is stat The expiry d month.

Reconstitute The reconstit to be stable f 8 hours at 25

From a micro should be us

above 25°C. Store in the original rder to protect from light.

uld not be used after the expiry date ed on the vial label and the carton. ate refers to the last day of that d solution

uted solution has been demonstrated or 24 hours at 2 °C – 8 °C and for °C.

biological point of view, the product ed immediately after reconstitution.

If not used i and conditio of the user a than 24 hour

6. Contents

What Actilys

• The active contains 1 20 mg (cor 50 mg (cor alteplase. A DNA techn

  mmediately, in-use storage times ns prior to use are the responsibility nd would normally not be longer s at 2 – 8°C.

  of the pack and other information e contains

  substance is alteplase. Each vial 0 mg (corresponding to 5,800,000 IU), responding to 11,600,000 IU) or responding to 29,000,000 IU) lteplase is produced by recombinant ique using a Chinese hamster ovary cell-line. Th phosphori polysorbat

• The solven

What Actilys

Actilyse is a injection and

Each pack co one vial with

Actilyse is av

e other ingredients are arginine, c acid (for pH-adjustment) and e 80.

t is water for injections.

e looks like and contents of the pack powder and solvent for solution for infusion.

ntains one vial with powder and the solvent.

ailable 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

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

Germa

ny

This le

aflet was last revised in 04/2021.

Package leaflet: Information for the user

Actilyse® powder and

ab

cd solvent for solution f

or

injection and infusio

n

10 mg, 20 mg and 50

mg

alteplase

A B

D

C

MASS A 25,5 mm MASS B 2,2 mm MASS C max. 48 mm MASS D 3 mm

Posology and method of administration

Acute myocardial infarction

Posology

1. a)

   90 minutes (accelerated) dose regimen for patients

   with acute myocardial infarction, in whom treatment can be started within 6 hours after symptom onset.

In patients with a body weight ≥ 65 kg:

he total dose

the following

ute myocardial

started

m onset.

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 and is for immediate use. 2 mg vials of alteplase are not indicated for use in this indication.

Acute massive pulmonary embolism

In patients with a body weight < 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 and is for immediate use. 2 mg vials of alteplase are not indicated for use in this indication.

Acute ischaemic stroke

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.

Treatment with Actilyse must be started as early as possible within 4.5 hours of the onset of symptoms (see SmPC section 4.4). 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).

Posology

The recommended total dose is 0.9 mg alteplase/kg body weight (maximum of 90 mg) starting with 10% of the total dose as an initial intravenous bolus, immediately followed by the remainder of the total dose infused intravenously over 60 minutes.

*given in a concentration of 1 mg/mL over 60 min as a constant rate infusion.

Adjunctive therapy: The safety and efficacy of this regimen with concomitant administration of heparin or platelet aggregation inhibitors such as acetylsalicylic acid within the first 24 hours of onset of the symptoms have not been sufficiently investigated. Therefore, administration of intravenous heparin or platelet aggregation inhibitors such as acetylsalicylic acid should be avoided in the first 24 hours after treatment with Actilyse due to an increased haemorrhagic risk. 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 and is for immediate use. 2 mg vials of alteplase are not indicated for use in this indication.

Paediatric population

There is limited experience with the use of Actilyse in children and adolescents. Actilyse is contraindicated for the treatment of acute ischaemic stroke in children and adolescents under 16 years of age (see SmPC section 4.3). The dose for adolescents 16-17 years old is the same as for adults (see SmPC section 4.4 for recommendations on prior imaging techniques to be used).

Adolescents of 16 years of age or older should be treated according to the instruction in the label for the adult population after imaging by appropriate techniques to rule out stroke mimics and confirming arterial occlusion corresponding to the neurological deficit.

The following information is intended for healthcare professionals only:

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

2 mg vials of alteplase are not indicated for use in the indications acute myocardial infarction, acute massive pulmonary embolism or acute ischaemic s

risk of massive under dosing). Only 10 mg,

50 mg vials are indicated for use in these i

Reconstitution

For reconstitution to a final concentration

alteplase per ml the full volume of solvent

should be transferred to the vial containin

powder. To this purpose a transfer cannula

with the 20 mg and 50 mg pack sizes, whic

used. For the 10 mg vial a syringe should b

For reconstitution to a final concentration

alteplase per ml only half of the solvent pr

should be used (as per table below). In the

always a syringe should be used to transfe

required amount of solvent to the vial con

Actilyse powder.

Under aseptic conditions the content of an

vial of Actilyse (10 mg or 20 mg or 50 mg) i

with water for injections according to the f

table to obtain either a final concentration

alteplase/ml or 2 mg alteplase/ml:

The reconstituted solution should then be administered intravenously. The 1 mg/mL reconstituted solution may be diluted further with sterile sodium chlo

(0.9 %) solution for injection up to a minima

concentration of 0.2 mg/ml since the occur

turbidity of the reconstituted solution can

excluded. A further dilution of the 1mg/mL

reconstituted solution with sterilised wate

injections or in general, the use of carbohy

infusion solutions, e.g. dextrose is not reco

due to increasing formation of turbidity of

reconstituted solution. Actilyse should not

with other medicinal products in the same

vial (not even with heparin).

For storage conditions, please see section

leaflet.

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

Instructions for reconstituting Actilyse

(*if a transfer cannula is included in the kit. The reconstitution can also be performed with a syringe and a needle.)

307453-09