SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET

1

SUMMARY OF PRODUCT CHARACTERISTICS

2 1. NAME OF THE MEDICINAL PRODUCT

[To be completed nationally Actilyse Cathflo 2 mg Powder and solvent 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.

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Powder and solvent for solution for injection and infusion.

The powder is presented as a colourless to pale yellow lyophilizate cake.

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 for use in this indication.

4.2 Posology and method of administration

Actilyse Cathflo should be given as soon as possible after symptom onset. 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.

3 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 prior to reconstitution prior to administration, see section 6.6.

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 . 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.

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. Hypersensitivity to the active substance or to any of the excipients.

4.4 Special warnings and precautions for use

2 mg vials are not indicated for use in the indications myocardial infarction, pulmonary embolism or acute ischaemic stroke (due to risk of massive underdosing). Only 10, 20 or 50 mg vials are indicated for use in those indications.

Special warnings and precautions in the treatment of occluded central venous access devices including those used for haemodialysis:

General: The coadministation 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 reocclusion 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 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.

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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 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 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. Although physiologically relevant plasma concentrations are not reached, hypersensitivity might occur. Anaphylactoid reactions associated with the administration of Actilyse Cathflo can be caused by hypersensitivity to the active substance alteplase, gentamicin (a trace residue from the manufacturing process) or to any of the excipients. The stopper of the glass vial with Actilyse Cathflo powder contains natural rubber (a derivative of latex) which may cause allergic reactions.

If an anaphylactoid reaction occurs, the instillation should be discontinued and appropriate treatment should be initiated.

Re-administration: Patients may receive up to 2 mg alteplase administered up to two times for any one occlusion. In the event of continuing catheter dysfunction other causes for dysfunction should be sought. Subsequent occlusions may be treated similarly although it should be noted that frequent re-occlusions may indicate the need for catheter replacement. Antibody formation in patients receiving one or more doses of alteplase for restoration of dysfunctional central venous access devices has not been studied.

4.5 Interaction with other medicinal products and other forms of interaction

The risk of haemorrhage is increased if coumarine derivatives, oral , aggregation inhibitors, unfractionated heparin or LMWH or other agents inhibiting 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 an anaphylactoid reaction, as in the cases describing such reactions a relatively larger proportion of patients were receiving ACE inhibitors concomitantly.

4.6 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 breast milk.

4.7 Effects on ability to drive and use machines

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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:

Infections and infestations uncommon: sepsis

General disorders and administration site conditions uncommon: catheter related complications rare: fever

In general, all undesirable effects as found for the systemic application of Actilyse (10, 20, 50 mg of alteplase) 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/anaphylactoid reactions, blood pressure decreased, nausea, vomiting, body temperature increased).

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 or fresh blood is recommended and if necessary, synthetic may be administered.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: agent, ATC code: B 01 A D 02

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.

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

6 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 t1/2 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, dilute Polysorbate 80

Solvent: Water for injections

The pH of the reconstituted solution is 7.3 ± 0.5.

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.

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

6.3 Shelf life

2 mg pack size: 3 years

After reconstitution, an immediate use is recommended. However, the in-use stability has been demonstrated for 24 hours at 2 °C – 8 °C and for 8 hours at 25 °C.

6.4 Special precautions for storage

Store in the original package in order to protect from light. For 2 mg pack size: Store in a refrigerator (2 – 8 °C). For storage conditions of the reconstituted 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.

Solvent: For the 2 mg pack size the water for injections is filled into 5 ml sterilised glass ampoules. The water for injections vials are sealed with rubber stoppers and aluminium/plastic flip-off caps.

Pack sizes:

5 vials with 93 mg powder for solution for injection and infusion 5 ampoules with 2.2 ml of water for injections

6.6 Special precautions for disposal and other handling

2 mg vials of alteplase are not indicated for use in the indications myocardial infarction, pulmonary embolism or ischaemic stroke (due to risk of massive underdosing).

The 2 mg vial should always be reconstituted to a final concentration of 1 mg alteplase per ml.

To this end, the full volume of solvent provided should be transferred to the vial containing the Actilyse Cathflo powder by use of a syringe.

Under aseptic conditions the content of an injection vial of Actilyse Cathflo (2 mg,) is dissolved with water for injections according to the following table to obtain a final concentration of 1 mg alteplase/ml:

Actilyse Cathflo vial 2 mg Volume of water for injections to be added to dry powder: Final concentration (a) 1 mg alteplase/ml 2.2 (ml) (b) 2 mg alteplase/ml not recommended (ml)

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

8 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 agitated 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 should be discarded.

7. MARKETING AUTHORISATION HOLDER

<[To be completed nationally]>

8. MARKETING AUTHORISATION NUMBER(S)

<[To be completed nationally]>

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: Date of last renewal:

10. DATE OF REVISION OF THE TEXT

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LABELLING

10 PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON (2 MG PACK SIZE/ 5 VIALS + 5 AMPOULES)

1. NAME OF THE MEDICINAL PRODUCT

[To be completed nationally]

Actilyse Cathflo 2 mg Powder and solvent for solution for injection and infusion alteplase

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each vial contains 2 mg alteplase corresponding to 1,160,000 IU). Alteplase is produced by recombinant DNA technique using a Chinese hamster ovary cell-line.

3. LIST OF EXCIPIENTS

Each vial with powder also contains arginine, phosphoric acid (dilute) and polysorbate 80. Solvent: water for injections

4. PHARMACEUTICAL FORM AND CONTENTS

Powder and solvent for solution for injection and infusion 5 vials of powder, each containing 2 mg alteplase 5 ampoules, each with 2.2 ml solvent

5. METHOD AND ROUTE(S) OF ADMINISTRATION

RECONSTITUTION Add 2.2 ml water for injections to a 2 mg vial of Actilyse Cathflo. Agitate gently until dissolved. DO NOT SHAKE.

Read the package leaflet before use. For catheter clearance only.

[PARTICULARS TO APPEAR ON THE INNER SIDE OF THE LID OF THE CARTON] For catheter clearance only.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE REACH AND SIGHT OF CHILDREN

Keep out of the reach and sight of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

11 8. EXPIRY DATE

EXP For storage of the reconstituted solution read the package leaflet.

9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator (2 – 8 °C). Store in the original package in order to protect from light.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

[To be completed nationally]

12. MARKETING AUTHORISATION NUMBER(S)

[To be completed nationally]

13. BATCH NUMBER

Batch

14. GENERAL CLASSIFICATION FOR SUPPLY

[To be completed nationally]

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

[Justification for not including Braille accepted]

12 MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

VIAL LABEL FOR POWDER FOR SOLUTION FOR INJECTION AND INFUSION (2 MG PACK SIZE)

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

[To be completed nationally]

Actilyse Cathflo 2 mg Powder for use in catheter clearance only alteplase

2. METHOD OF ADMINISTRATION

Read the package leaflet before use.

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Batch

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

6. OTHER

Store at 2 – 8 °C. Protect from light.

13 MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

VIAL LABEL FOR SOLVENT (2 MG PACK SIZE)

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Solvent for Actilyse Cathflo 2 mg

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Batch

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

2.2 ml water for injections

6. OTHER

Do not store above 25 °C. Protect from light.

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PACKAGE LEAFLET

15 PACKAGE LEAFLET: INFORMATION FOR THE USER

Actilyse Cathflo 2 mg Powder and solvent for solution for injection and infusion [To be completed nationally (the strength can be included here optionally)] Alteplase

Read all of this leaflet carefully before you start using this medicine. - Keep this leaflet. You may need to read it again. - If you have any further questions, ask your doctor. - This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours. - If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

In this leaflet: 1. What Actilyse Cathflo is and what it is used for 2. Before you receive Actilyse Cathflo 3. How is Actilyse Cathflo administered 4. Possible side effects 5. How to store Actilyse Cathflo 6. Further information

1. WHAT ACTILYSE CATHFLO IS AND WHAT IT IS USED FOR

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

Actilyse Cathflo is used to clear catheters which are blocked by blood clots.

2. BEFORE YOU RECEIVE ACTILYSE CATHFLO

Actilyse Cathflo will not be given by your doctor, • if you are allergic (hypersensitive) to the active substance alteplase, to gentamicin (a trace residue from the manufacturing process), to natural rubber (also called latex which is part of the packaging material) or to any of the other ingredients of this medicine Actilyse Cathflo (listed insee section 6: “Further information”).

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 located in the catheter

16 Taking other medicines Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. It is particularly important that you tell your doctor if you are taking or have recently taken: • any medicines which are used to “thin “ the blood, including:  aspirin  warfarin  coumarin  heparin • certain medicines used to treat high blood pressure (ACE inhibitors).

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

3. HOW IS ACTILYSE CATHFLO ADMINISTERED

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

Actilyse Cathflo is supplied as a powder and solvent. This means that each pack contains one or more vials with powder and an equal amount of ampoules with the solvent (water for injections). Before use, the solvent is added to the powder to form a solution ready for 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 Actilyse Cathflo, ask your doctor.

4. POSSIBLE SIDE EFFECTS

Like all medicines, Actilyse Cathflo 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)

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• fever

In general, all undesirable effects as found for the systemic application of Actilyse (10, 20, 50 mg of alteplase) may also occur during treatment of catheters blocked by blood clots in cases where Actilyse Cathflo (2 mg of alteplase) reaches the blood circulation (e.g. bleeding (haemorrhage), sudden blocking of a blood vessel (embolism), allergic (hypersensitivity/anaphylactoid) reactions, blood pressure decreased, nausea, vomiting, body temperature increased).

Tell your doctor immediately if you think you are experiencing one of these side effects.

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

5. HOW TO STORE ACTILYSE CATHFLO

Keep out of the reach and sight of children.

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

Normally you will not be asked to store Actilyse Cathflo as it will be given to you by your doctor. Actilyse Cathflo should be stored in a refrigerator (2 – 8 °C). Store in the original package in order to protect from light.

Once the solution is ready for administration, it should be used immediately. When necessary however, the solution may be stored for 24 hours at 2 °C – 8 °C or for 8 hours at up to 25 °C. However your doctor will normally use the solution immediately.

6. FURTHER INFORMATION

What Actilyse Cathflo contains

- The active substance is alteplase. Each vial contains 2 mg (corresponding to 1,160,000 IU) alteplase. Alteplase is produced by means of recombinant DNA technique using a Chinese hamster ovary cell- line. - The other ingredients are arginine, phosphoric acid (dilute) and polysorbate 80. - The solvent is water for injections. - The rubber stopper of the packaging material contains natural rubber (latex)

What Actilyse Cathflo looks like and contents of the pack

Actilyse Cathflo is a powder and solvent for solution for instillation into a blocked catheter. This means that each complete pack contains several vials with powder and an equal amount of ampoules with the solvent.

For clearance of blocked catheters Actilyse Cathflo is available in the following complete pack:

- Five vials, each with 2 mg alteplase, and five ampoules, each with 2.2 ml water for injections.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

<[To be completed nationally]>

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Manufacturer

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

This leaflet was last approved in {MM/YYYY}.

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Due to the nature of this medicinal product it is considered important that healthcare professionals have access to the full scientific information at the point of use. The complete SPC will therefore be provided as a separate document in the product package.

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