Pharmaceutical particulars : מידע רוקחי

6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Powder:
L-arginine
Phosphoric acid
Polysorbate 80
Solvent:
Water for injections

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.

Actilyse should not be mixed with other medicinal products neither in the same infusion vial nor the same catheter (not even with heparin).

6.3 Shelf life

Unopened vials
The expiry date of the product is indicated on the packaging materials Reconstituted solution
The reconstituted solution has been demonstrated to be stable 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.
Actilyse                                                                  Updated Prescribing Information  20 mg, 50 mg                                                                                     Feb 2023
6.4 Special precautions for storage

Store in the original package in order to protect from light.
Do not store above 25°C.
For storage conditions after reconsititution of the medicinal product, see section 6.3.
6.5 Nature and contents of container
Powder:
20 ml or 50 ml sterilised glass vials, sealed with sterile siliconised grey butyl-type stoppers with aluminium/plastic flip-off caps.
Solvent:
For the 20 mg and 50 mg pack sizes, the water for injections is filled into either 20 ml or 50 ml vials, depending on the size of the powder vials. The water for injections vials are sealed with rubber stoppers and aluminium/plastic flip-off caps.

Transfer cannulas

Presentations:
20 mg:
1 vial with 933 mg powder for solution for injection and infusion
1 vial with 20 ml of water for injections
1 transfer cannula
50 mg
1 vial with 2333 mg powder for solution for injection and infusion.
1 vial with 50 ml of water for injections.
1 transfer cannula.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling
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 pack, which is to 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 (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 dry substance                 20 mg                   50 mg
(a) Volume of sterilised water for injections to be added to dry          20 mL                   50 mL substance
Final concentration:                   1 mg alteplase/mL       1 mg alteplase/mL (b) Volume of sterilised water for injections to be added to dry          10 mL                   25 mL substance
Final concentration:                   2 mg alteplase/mL       2 mg alteplase/mL Actilyse                                                               Updated Prescribing Information  20 mg, 50 mg                                                                                  Feb 2023
The reconstituted solution should then be administered intravenously. The 1 mg/mL reconstituted solution 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 since the occurrence of turbidity of the reconstituted solution cannot be excluded. A further dilution of the 1 mg/mL reconstituted solution with sterilised water for injections 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. Actilyse should not be mixed with other medicinal products in the same infusion-vial (not even with heparin).

For incompatibilities see section 6.2.

The reconstituted solution is for single use only. Any unused solution or waste material should be disposed in accordance with the local requirements.

Instructions for reconstituting Actilyse

1     Reconstitute immediately before administration.


2     Remove the protective cap on the two vials containing the sterile water and Actilyse dry substance by flipping them up with a thumb.



3     Swab the rubber top of each vial with an alcohol wipe.
Actilyse                                                      Updated Prescribing Information 20 mg, 50 mg                                                                         Feb 2023
4    Remove the transfer cannula from its cover. Do not disinfect or sterilize the transfer cannula; it is sterile. Take one cap off.



5    Stand the sterile water vial upright on a stable surface. From directly above, puncture the rubber stopper vertically in the stopper center with the transfer cannula, by pressing gently but firmly, without twisting.



6    Hold the sterile water vial and the transfer cannula steady with one hand using the two side flaps.
Remove the remaining cap on top of the transfer cannula.
Actilyse                                                   Updated Prescribing Information 20 mg, 50 mg                                                                      Feb 2023
7    Hold the sterile water vial and the transfer cannula steady with one hand using the two side flaps.

Hold the vial with Actilyse dry substance vertically above the transfer cannula and position the tip of the transfer cannula right in the center of the stopper.



Push down the vial with the dry substance onto the transfer cannula from directly above,
puncturing the rubber stopper vertically and gently but firmly without twisting.


8    Invert the two vials and allow the water to drain completely into the dry substance.
Actilyse                                             Updated Prescribing Information 20 mg, 50 mg                                                                Feb 2023


9    Remove the empty water vial together with the transfer cannula.
They can be disposed of.
Actilyse                                                               Updated Prescribing Information 20 mg, 50 mg                                                                                  Feb 2023
10   Take the vial with reconstituted Actilyse and swirl gently to dissolve any remaining powder,
but do not shake, as this will produce foam.



If there are bubbles, let the solution stand undisturbed for a few minutes to allow them to disappear.



11   The reconstituted solution consists of 1mg/mL alteplase. It should be clear and colourless to pale yellow and it should not contain any particles.

12   Remove the amount required only by using a needle and a syringe.
Do not use the puncture location from the transfer cannula to avoid leakage.



13   Use immediately.
Dispose of any unused solution.
Actilyse                                                     Updated Prescribing Information  20 mg, 50 mg                                                                        Feb 2023