ACTILYSE CATHFLO

Ireland - English - HPRA (Health Products Regulatory Authority)

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Active ingredient:
ALTEPLASE
Available from:
Boehringer Ingelheim Limited
ATC code:
B01AD02
INN (International Name):
ALTEPLASE
Dosage:
2 Milligram
Pharmaceutical form:
Pdr+Solv for soln for inf/inj
Prescription type:
Product subject to prescription which may not be renewed (A)
Therapeutic area:
alteplase
Authorization status:
Marketed
Authorization number:
PA0007/043/005
Authorization date:
2010-04-09

PACKAGE LEAFLET:

INFORMATION FOR THE USER

Actilyse

Cathflo

2 mg

powder for solution for

injection and infusion

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.

- 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.

What is in this leaflet:

1. What Actilyse Cathflo is and what

it is used for

2. What you need to know before you

receive Actilyse Cathflo

3. How is Actilyse Cathflo

administered

4. Possible side effects

5. How to store Actilyse Cathflo

6. Contents of the pack and other

information

1.

What Actilyse Cathflo is and

what it is used for

The active substance in Actilyse

Cathflo is alteplase. It belongs to a

group of medicines called

thrombolytic agents. These

medicines act by dissolving blood

clots.

2.

What you need to know before

you get Actilyse Cathflo

You should not receive Actilyse

Cathflo

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).

Your doctor will take special care

with Actilyse Cathflo

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 a bleeding in any part of

the body

if in the past 48 hours you have had

a condition that increases your risk

of bleeding, including:

surgery

biopsy (a procedure for obtaining

a tissue specimen)

puncture

delivery of a baby

if you have a bleeding disorder or

tendency to bleed

if you have severe liver or kidney

disease

if a blood vessel located close to

the catheter is blocked by blood

clots (venous thrombosis)

if there is or may be an infection

located in the catheter

Other medicines and Actilyse Cathflo

Tell your doctor if you are taking,

have recently taken or might take 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:

acetylsalicylic acid

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 Cathflo if the

possible benefit outweighs the

possible risk to your baby.

Actilyse Cathflo may contain

gentamicin as trace residue from the

manufacturing process; the

packaging contains natural rubber

(latex).

3.

How is Actilyse Cathflo

administered

Actilyse Cathflo will be prepared and

administered to you by your doctor

or by a health care professional. It is

not for self-administration.

The dose you are given depends on

your body weight. The maximum

dose of Actilyse Cathflo is 2 mg but

will be lower if you weigh less than

30 kg.

Actilyse Cathflo is filled in the

blocked catheter. After 30 min your

doctor will check if the catheter has

already been cleared. If this is the

case, treatment with Actilyse Cathflo

will be stopped. If this is not yet the

case, the product will remain in the

catheter for another 90 min.

After treatment, Actilyse Cathflo is

removed from the catheter. The

catheter is rinsed with sterile saline

solution.

If the catheter is still blocked after

your first treatment with Actilyse

Cathflo, the whole procedure may be

repeated once.

Actilyse Cathflo should not be mixed

with other medicines.

If you have any further questions on

the use of this medicine, ask your

doctor or nurse.

4.

Possible side effects

Like all medicines, this medicine can

cause side effects, although not

everybody gets them.

The side effects described below

have been experienced by people

given Actilyse Cathflo:

Uncommon (occurs in less than 1 in

100 patients receiving the medicine)

release of an infection from the

catheter to the blood vessels

leading to blood poisoning (sepsis)

damage to the catheter such as:

blockage

leakage

burst

Rare (occurs in less than 1 in 1,000

patients receiving the medicine)

fever

In principle, all undesirable effects as

found for the application of Actilyse

(10, 20, 50 mg of alteplase) for heart

attacks, pulmonary embolism or

stroke may also occur during

treatment of catheters blocked by

blood clots. This is however only

possible in cases where Actilyse

Cathflo (2 mg of alteplase) reaches

the blood circulation. The following

side effects may occur: e.g. bleeding

(haemorrhage), sudden blocking of a

blood vessel (embolism), allergic

(hypersensitivity/anaphylactoid)

reactions, blood pressure decreased,

nausea, vomiting, body temperature

increased. However none of these

side effects has ever been observed

with Actilyse Cathflo so far. Due to

the small amount of medicine used,

these side effects are very unlikely to

occur with Actilyse Cathflo (2 mg) –

apart from allergic reactions for

which a small amount may be

sufficient. When using the product

Actilyse (10, 20, 50 mg of alteplase),

allergic reactions have been observed

rarely.

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 on the

safety of this medicine.

United Kingdom

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

Ireland

HPRA Pharmacovigilance

Earlsfort Terrace

IRL – Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.hpra.ie

e-mail: medsafety@hpra.ie

abcd

Actilyse Cathflo is used to clear

catheters which are blocked by

blood clots.

File information

Issue date of TD:

PPM SKU:

PPM SKU version:

Issue date of artwork:

Print colors:

PAN Black

15.01.2015

P035389

15.11.2012

Yes

Yes

No

Yes

No

Yes

No

Yes

No

No

Yes

Yes

TD

Printfile

Mandatory in

Mat. No. Pack. Site:

Min. font size:

307972-01

12pt

Legend case version:

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

a = Batch No.

b = Expiry date

c = Manufacturing date

d = Price/Sample/Clinic

Technical colors

BI-Diecut-Legendcase

Free area

Gluepoints

Technical information

Template name: TD-PI_160x630

Index: b

Additional Requirements of Packaging site

MASS

8,5 mm

MASS

2,2 mm

MASS

max. 42,5 mm

5.

How to store Actilyse Cathflo

Normally you will not be asked to

store Actilyse Cathflo as it will be

given to you by your doctor.

Keep this medicine out of the sight

and reach of children.

Store in a refrigerator (2 – 8 °C).

Store in the original package in order

to protect from light.

Do not use this medicine after expiry

date which is stated on the vial label

and the carton. The expiry date refers

to the last day of that month.

After reconstitution: From a

microbiological point of view, the

product should be used immediately

after reconstitution. If not used

immediately, in-use storage times

and conditions prior to use are the

responsibility of the user and would

normally not be longer than 24 hours

at 2 – 8°C.

6.

Contents of the pack and other

information

What Actilyse Cathflo contains

The active substance is alteplase. Each

vial contains 2 mg (corresponding

to 1,160,000 IU) alteplase.

The other ingredients are arginine,

phosphoric acid (for pH-adjustment)

and polysorbate 80.

The rubber stopper of the

packaging material contains natural

rubber (latex)

What Actilyse Cathflo looks like and

contents of the pack

Actilyse Cathflo is a powder for

solution for injection and infusion.

Each pack contains five vials, each with

2 mg alteplase.

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 01/2015.

© Boehringer Ingelheim Limited 2015

307972-01

The following information is

intended for medical or healthcare

professionals only:

Instructions for reconstitution

The 2 mg presentation of alteplase is

not indicated for use in myocardial

infarction, acute pulmonary embolism

or acute ischaemic stroke (due to risk

of massive underdosing). Only 10, 20

or 50 mg presentations are indicated

for use in those indications.

The 2 mg vial (with a total amount of

2.2 mg alteplase including 0.2 mg

overage which will remain in the

transfer syringe so that the amount

practically administered is 2 mg

alteplase) should always be

reconstituted to a final concentration

of 1 mg alteplase per ml.

To this end, 2.2 mL sterile water for

injection should be transferred to the

vial containing the Actilyse Cathflo

powder by use of a syringe with a

suitable measuring precision under

aseptic conditions.

The reconstituted solution should

then be instilled into the dysfunctional

central venous access device. 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 Cathflo

should not be mixed with other

medicinal products in the same

catheter (not even with heparin).

For incompatibilities see section 6.2

of the SmPC.

When reconstituting the product

from the respective amount of

powder and solvent, the mixture

should only be swirled gently until

complete dissolution. Any vigorous

agitation should be avoided to

prevent foam formation.

The reconstituted preparation is a

clear and colourless to pale yellow

solution. Prior to administration it

should be inspected visually for

particles and colour.

For storage conditions, please see

section 5 of this leaflet.

The reconstituted solution is for

single use only. Any unused solution

should be discarded.

Instructions for administration in

occluded central venous access

devices including those used for

haemodialysis

1. Reconstitute the content of an

injection vial to a final concentration

of 1 mg alteplase per ml. For

catheters with a lumen volume

greater than 2 ml, the reconstituted

solution can be further diluted with

sterile sodium chloride 9 mg/ml

(0.9 %) solution for injection to the

desired volume. I.e. for a catheter

with internal volume of 2.5 ml the

total dose of Actilyse Cathflo would

be 2.0 mg in a volume of 2.5 ml.

2. Instil the appropriate dose of

Actilyse Cathflo into the

dysfunctional central venous

access device.

3. After 30 minutes of dwell time,

assess catheter function by

attempting to aspirate blood. If the

catheter is functional, go to Step 6.

If the catheter is not functional, go

to Step 4.

4. After 120 minutes of dwell time,

assess catheter function by

attempting to aspirate blood and

catheter contents. If the catheter is

functional, go to Step 6. If the

catheter is not functional, go to

Step 5.

5. If catheter function is not restored

after the first dose, a second dose

of equal amount may be instilled.

Repeat the procedure beginning

with Step 1. If after a second dose

of alteplase the device remains

dysfunctional consider device

replacement.

6. If catheter function has been

restored, aspirate 4–5 ml of blood

in patients weighing 10 kg or more,

or 3 ml in patients with a body

weight below 10 kg to remove

Actilyse Cathflo and residual clot,

and gently irrigate the catheter

with sterile sodium chloride

9 mg/ml (0.9 %) solution for

injection.

------------------------------------------------------------------------------------

Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Actilyse Cathflo 2 mg powder for solution for injection and infusion.

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

1 vial with powder contains:

2 mg alteplase (corresponding to 1,160,000 IU)

Alteplase is produced by recombinant DNA technique using a Chinese hamster ovary cell-line. The specific activity of

alteplase in-house reference material is 580,000 IU/mg. This has been confirmed by comparison with the second

international WHO standard for t-PA. The specification for the specific activity of alteplase is 522,000 to 696,000

IU/mg.

Each constituted vial will deliver 2 mg of alteplase.

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Powder

for solution for injection and infusion.

The powder is presented as a colourless to pale yellow lyophilizate cake. The reconstituted preparation is a clear and

colourless to pale yellow solution.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

Thrombolytic treatment of occluded central venous access devices including those used for haemodialysis

The 2 mg vial is the only recommended presentation of alteplase for use in this indication.

4.2 Posology and method of administration

Actilyse Cathflo should be given as soon as possible after occlusion. The following dose guidelines apply.

Posology

A dose of up to 2 mg alteplase administered up to two times for any one occlusion can be used to restore function of

ports, single and multiple lumen catheters including those used for haemodialysis, which became dysfunctional due to

thrombotic occlusion.

For use in this indication reconstitution to a final concentration of 1 mg alteplase per ml is recommended.

In patients with a body weight of 30 kg or more, a total dose of 2 mg alteplase in 2 ml of reconstituted solution should

be instilled into the dysfunctional central venous access device.

In patients with a body weight below 30 kg, the volume of reconstituted solution to be instilled into the dysfunctional

central venous access devices should correspond to 110% of the internal lumen volume of the device. The total dose of

alteplase should not exceed 2 mg. I.e. for a catheter with internal volume of 1.0 ml the total dose of Actilyse Cathflo

would be 1.1 mg in a volume of 1.1 ml.

If central venous access device function is not restored at 120 minutes after the first dose, a second dose of equal

amount may be instilled.

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Method of catheter clearance

The reconstituted solution should be instilled into the occluded central venous access device.

Only 2 mg vials of alteplase are indicated for use in this indication. For instructions on how to reconstitute the product

prior to administration, see section 6.6.

Reconstitute the content of an injection vial to a final concentration of 1 mg alteplase per ml. For catheters with a

lumen volume greater than 2 ml, the reconstituted solution can be further diluted with sterile sodium chloride 9

mg/ml (0.9 %) solution for injection to the desired volume. I.e. for a catheter with internal volume of 2.5 ml the

total dose of Actilyse Cathflo would be 2.0 mg in a volume of 2.5 ml.

Instil the appropriate dose of Actilyse Cathflo into the dysfunctional central venous access device.

After 30 minutes of dwell time, assess catheter function by attempting to aspirate blood. If the catheter is

functional, go to Step 6. If the catheter is not functional, go to Step 4.

After 120 minutes of dwell time, assess catheter function by attempting to aspirate blood and catheter contents. If

the catheter is functional, go to Step 6. If the catheter is not functional, go to Step 5.

If catheter function is not restored after the first dose, a second dose of equal amount may be instilled. Repeat the

procedure beginning with Step 1. If after a second dose of alteplase the device remains dysfunctional consider

device replacement.

If catheter function has been restored, aspirate 4–5 ml of blood in patients weighing 10 kg or more, or 3 ml in

patients with a body weight below 10 kg to remove Actilyse Cathflo and residual clot, and gently irrigate the

catheter with sterile sodium chloride 9 mg/ml (0.9 %) solution for injection.

Paediatric population

The Paediatric population is covered by the general dosing scheme as described above.

4.3 Contraindications

Actilyse Cathflo should not be administered to patients with known hypersensitivity to the active substance alteplase,

gentamicin (a trace residue from the manufacturing process) or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

The appropriate presentation of alteplase product should be chosen carefully and in accordance with the intended use.

The 2 mg presentation of alteplase is not indicated for use in acute myocardial infarction, acute 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 those

indications.

General:

The coadministration of heparin with Actilyse Cathflo has not been shown to improve the rates of catheter function

restoration and is not recommended. If heparin is considered necessary to prevent re-occlusion this should be

administered separately after catheter function has been restored.

Catheter dysfunction may be caused by a variety of conditions other than thrombus formation, such as catheter

malposition, mechanical failure, constriction by a suture, and lipid deposits or drug precipitates within the catheter

lumen. Because of the risk of damage to the vascular wall or collapse of soft-walled catheters, vigorous suction should

not be applied during attempts to determine catheter occlusion. Excessive pressure should be avoided when Actilyse

Cathflo is instilled into the catheter. Such force could cause rupture of the catheter or expulsion of the clot into the

circulation.

Particular caution is necessary if small volume syringes (

1 ml) are used for application, especially if small volume

catheters are used as typical in the paediatric population.

Bleeding:

The most frequent adverse reaction associated with all thrombolytics in all approved indications is bleeding.

Actilyse

Cathflo has not been studied in patients with occluded catheters known to be at risk for bleeding events that may be

associated with the use of thrombolytics. Caution should be exercised with patients who have active internal bleeding

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or who have had any of the following within 48 hours: surgery, obstetrical delivery, percutaneous biopsy of viscera or

deep tissues, or puncture of non-compressible vessels. In addition, caution should be exercised with patients who have

thrombocytopenia, other haemostatic defects (including those secondary to severe hepatic or renal disease), or any

condition for which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its

location, or who are at high risk for embolic complications (e.g., venous thrombosis in the region of the catheter).

Death and permanent disability have been reported in patients who have experienced stroke and other serious bleeding

episodes when receiving pharmacologic doses of a thrombolytic. Should serious bleeding in a critical location (e.g.,

intracranial, gastrointestinal, retroperitoneal, pericardial) occur, treatment with Actilyse Cathflo should be stopped and

the drug should be withdrawn from the catheter.

Infection:

Using Actilyse Cathflo in patients whose catheters are occluded by infected thrombi may release microorganisms into

the systemic circulation leading to sepsis. As with all catheterisation procedures, care should be taken to maintain

aseptic technique and appropriate antibiotic treatment used as necessary.

Hypersensitivity

Antibody formation in patients receiving one or more doses of alteplase for restoration of dysfunctional central venous

access devices has not been studied. Hypersensitivity reactions associated with the administration of Actilyse Cathflo

can be caused by the active substance alteplase, gentamicin (a trace residue from the manufacturing process), any of the

excipients, or the stopper of the glass vial with Actilyse Cathflo powder which contains natural rubber (a derivative of

latex).

If a severe hypersensitivity reaction occurs, the instillation should be discontinued and appropriate treatment should be

promptly initiated.

4.5 Interaction with other medicinal products and other forms of interaction

No formal interaction studies with Actilyse Cathflo have been performed.

The risk of haemorrhage is increased if coumarine derivatives, oral anticoagulants, platelet aggregation inhibitors,

unfractionated heparin or LMWH or other agents inhibiting coagulation are administered (before, during or within the

first 24 hours after treatment with Actilyse Cathflo).

Concomitant treatment with ACE inhibitors may enhance the risk of suffering a hypersensitivity reaction.

4.6 Fertility, pregnancy and lactation

There is very limited experience with the use of alteplase during pregnancy and lactation. Studies in animals have

shown reproductive toxicity (see section 5.3). In cases of an acute life-threatening disease the benefit has to be

evaluated against the potential risk. It is not known if alteplase is excreted into human milk.

4.7 Effects on ability to drive and use machines

Not relevant.

4.8 Undesirable effects

Adverse reactions listed below are classified according to frequency and system organ class. Frequency groupings are

defined according to the following convention: Very common (

1/10), Common (

1/100 to <1/10), Uncommon

1/1,000 to <1/100), Rare (

1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the

available data).

In clinical trials investigating treatment of occluded catheters with Actilyse Cathflo the following undesirable effects

were observed:

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Under systemic application of alteplase (i.e. high dose in thrombo-embolic indications), the following dose-

independent side effects have been reported:

*See sections 4.4 and 4.5

In principle, all undesirable effects as found for the systemic application of Actilyse (using the 10, 20, 50 mg

presentations of alteplase, please refer to respective SmPC) may also occur during treatment of occluded catheters in

cases where Actilyse Cathflo (2 mg of alteplase) reaches the systemic circulation (e.g. haemorrhage, embolism,

hypersensitivity reactions, blood pressure decreased, nausea, vomiting, body temperature increased). However,

pharmacokinetic data indicate that physiologically relevant plasma concentrations are not reached using this dosage.

Immune system disorders, on the other hand, can be regarded dose-independent and have therefore been copied from

the systemic application; immune system disorders have however not been observed in clinical trials with Actilyse

Cathflo.

Paediatric Population

Based on clinical study data, the safety profile for use in children is comparable with the one observed in adults.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued

monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any

suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971;

Fax: +353 1 6762517. Website:

http://www.hpra.ie/; e-mail: medsafety@hpra.ie.

4.9 Overdose

The relative fibrin specificity notwithstanding, a clinical significant reduction in fibrinogen and other blood coagulation

components may occur after overdosage. In most cases, it is sufficient to await the physiological regeneration of these

factors after the Actilyse Cathflo therapy has been terminated. If, however, severe bleeding results, the infusion of fresh

frozen plasma is recommended and if necessary, synthetic antifibrinolytics may be administered.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antithrombotic agents, ATC code: B01AD02

Alteplase is a recombinant human tissue-type plasminogen activator, a glycoprotein, which activates plasminogen

directly to plasmin. When administered intravenously, alteplase remains relatively inactive in the circulatory system.

Once bound to fibrin, it is activated, inducing the conversion of plasminogen to plasmin leading to the dissolution of

the fibrin clot.

Class

Adverse reaction

Infections and infestations

uncommon

sepsis

General disorders and administration site

conditions

uncommon

catheter related complication

rare

pyrexia

Immune system disorders

rare

hypersensitivity reactions (e.g. rash, urticaria, bronchospasm, angio-oedema,

hypotension, shock)*

very rare

serious anaphylaxis

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Due to its relative fibrin-specificity alteplase at a dose of 100 mg leads to a modest decrease of the circulating

fibrinogen levels to about 60 % at 4 hours, which is generally reverted to more than 80 % after 24 hours. Plasminogen

and alpha-2-antiplasmin decrease to about 20 % and 35 % respectively after 4 hours and increase again to more than

80 % at 24 hours. A marked and prolonged decrease of the circulating fibrinogen level is only seen in few patients.

Occluded central venous access devices including those used for haemodialysis

In two clinical studies more than 1,100 mainly adult patients with improperly functioning central venous access devices

were treated with alteplase. Restoration rates of catheter function were between 74 % and 77 % following one dose and

between 87 % and 90 % following two doses of alteplase. In studies with haemodialysis catheters using dwell times

ranging from

2 hours to the next dialysis session comparable restoration rates were reported.

In a study of 310 children the overall rate of catheter function restoration of 83 % after up to two doses of alteplase was

similar to that observed in adults. A total of 432 patients under age of 17 have received a dose of up to 2 mg alteplase

for up to two administrations in pivotal trials of catheter clearance. Overall safety and efficacy results were similar in

the paediatric and adult patients.

5.2 Pharmacokinetic properties

Alteplase is cleared rapidly from the circulating blood and metabolised mainly by the liver (plasma clearance 550 - 680

ml/min.). The relevant plasma half-life t

alpha is 4-5 minutes. This means that after 20 minutes less than 10 % of the

initial value is present in the plasma. For the residual amount remaining in a deep compartment, a beta-half-life of

about 40 minutes was measured.

When Actilyse Cathflo is administered for restoration of dysfunctional central venous access devices according to the

instructions circulating plasma levels of alteplase are not expected to reach pharmacologic concentrations. If a 2 mg

dose of alteplase was administered by bolus injection directly into the systemic circulation (rather than instilled into the

catheter), the concentration of circulating alteplase would be expected to return to undetectable limits within 30-60

minutes.

5.3 Preclinical safety data

In subchronic toxicity studies in rats and marmosets no unexpected undesirable effects were found. No indications of a

mutagenic potential were found in mutagenic tests.

In pregnant animals no teratogenic effects were observed after intravenous infusion of pharmacologically effective

doses. In rabbits embryotoxicity (embryolethality, growth retardation) was induced by more than

3 mg/kg/day. No

effects on peri-postnatal development or on fertility parameters were observed in rats with doses up to 10 mg/kg/day.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Powder:

Arginine

Phosphoric acid (for pH-adjustment)

Polysorbate 80

6.2 Incompatibilities

The reconstituted solution may be diluted with sterile sodium chloride 9 mg/ml (0.9 %) solution for injection up to a

minimal concentration of 0.2 mg alteplase per ml.

Further dilution, the use of water for injections for dilution or in general the use of carbohydrate infusion solutions, e.g.

dextrose, is not recommended due to increasing formation of turbidity of the reconstituted solution.

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Actilyse Cathflo should not be mixed with other medicinal products (not even with heparin).

6.3 Shelf life

3 years

Chemical and physical in-use stability has been demonstrated for 24 hours at 2 °C – 8 °C and for 8 hours at 25 °C.

From a microbiological point of view, the product should be used immediately after reconstitution. If not used

immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not

be longer than 24 hours at 2 to 8°C.

6.4 Special precautions for storage

Store in the original package in order to protect from light.

Store in a refrigerator (2 – 8 °C).

For storage conditions after reconstitution of the medicinal product, see section 6.3.

6.5 Nature and contents of container

Powder:

2 ml sterilised glass vials, sealed with sterile siliconised grey butyl-type stoppers with aluminium/plastic flip-off caps.

Pack sizes:

5 vials with 93 mg powder for solution for injection and infusion.

6.6 Special precautions for disposal and other handling

The 2 mg presentation of alteplase is not indicated for use in myocardial infarction, acute pulmonary embolism or acute

ischaemic stroke (due to risk of massive underdosing). Only 10, 20 or 50 mg presentations are indicated for use in those

indications.

The 2 mg vial (with a total amount of 2.2 mg alteplase including 0.2 mg overage which will remain in the transfer

syringe so that the amount practically administered is 2 mg alteplase) should always be reconstituted to a final

concentration of 1 mg alteplase per ml.

To this end, 2.2 ml sterile water for injection should be transferred to the vial containing the Actilyse Cathflo powder

by use of a syringe with a suitable measuring precision under aseptic conditions.

The reconstituted solution should then be instilled into the dysfunctional central venous access device. 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 Cathflo should not be mixed with other medicinal

products in the same catheter (not even with heparin).

For incompatibilities see section 6.2.

When reconstituting the product from the respective amount of powder and solvent, the mixture should only be swirled

gently until complete dissolution. Any vigorous agitation should be avoided to prevent foam formation.

The reconstituted preparation is a clear and colourless to pale yellow solution. Prior to administration it should be

inspected visually for particles and colour.

The reconstituted solution is for single use only. Any unused solution or waste material should be disposed in

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accordance with the local requirements.

7 MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim Limited

Ellesfield Avenue

Bracknell

Berkshire

RG12 8YS

United Kingdom

8 MARKETING AUTHORISATION NUMBER

PA0007/043/005

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 9

April 2010

Date of last renewal: 26

April 2009

10 DATE OF REVISION OF THE TEXT

May 2018

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