Pharmaceutical particulars : מידע רוקחי

6.    PHARMACEUTICAL PARTICULARS
6.1   List of excipients

Sucrose
Distearoylphosphatidylcholine
Distearoylphosphatidylglycerol
Copper gluconate
Cholesterol
Triethanolamine

6.2   Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

6.3   Shelf life

Unopened vials
The expiry date of the product is indicated on the packaging materials 
Stability of reconstituted suspension in the vial
Chemical and physical in-use stability has been demonstrated for 4 hours at 2°C to 8°C when kept in an upright position.
From a microbiological point of view, unless the method of opening/reconstitution/dilution precludes the risk of microbial contamination, the product should be used immediately.
If not used immediately, in-use storage times and conditions are the responsibility of the user.
Stability of diluted infusion solution
Chemical and physical in-use stability has been demonstrated for 4 hours at 2°C to 8°C.

From a microbiological point of view, unless the method of opening/reconstitution/dilution precludes the risk of microbial contamination, the product should be used immediately.
If not used immediately, in-use storage times and conditions are the responsibility of the user.

The maximum combined storage time for reconstituted product in the vial and reconstituted product diluted into an infusion bag is up to 4 hours at 2°C to 8°C.

6.4 Special precautions for storage
Store in a refrigerator (2°C – 8°C).

Keep the vial in the original carton in order to protect from light. Store in an upright position.
For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.

6.5   Nature and contents of container

50 mL vial (type 1 glass) with a stopper (chlorobutyl rubber), and an overseal (aluminium) containing 44 mg daunorubicin and 100 mg cytarabine.

Each pack contains either 1 vial, 2 vials or 5 vials. Not all pack sizes may be marketed.

6.6   Special precautions for disposal and other handling
Vyxeos liposomal is a cytotoxic medicinal product. Applicable special handling and disposal procedures should be followed. The product is intended for single use only. Any unused product should be disposed of in accordance with local requirements for cytotoxic agents.

Preparation instructions
•     Determine the dose and number of vials of Vyxeos liposomal based on the individual patient’s BSA as outlined in section 4.2.
•     Remove the appropriate number of vials of Vyxeos liposomal from the refrigerator and equilibrate to the room temperature (15°C to 30°C) for 30 minutes.
•     Then, reconstitute each vial with 19 mL of sterile water for injections using a 20 mL syringe, and immediately thereafter start a 5-minute timer.
•     Carefully swirl the contents of the vial for 5 minutes while gently inverting the vial every 30 seconds.
•     Do not heat, vortex, or shake vigorously.
•     After reconstitution, let it rest for 15 minutes.
•     The reconstituted product should be an opaque, purple, homogeneous dispersion, essentially free from visual particulates.
•     If the reconstituted product is not diluted into an infusion bag immediately, store in a refrigerator (2ºC to 8ºC) for up to 4 hours.
•     Following the storage of reconstituted product in the vial for up to 4 hours at 2°C to 8°C in an upright position, the reconstituted product must immediately be diluted into an infusion solution and run for the 90-minute infusion time.
o Reconstituted product in the vial and reconstituted product which has been diluted into an infusion solution are stable for a maximum combined storage time of up to 4 hours when stored at 2°C to 8°C, The 4-hour stability period for the reconstituted product in the vial does not allow for an additional 4-hour stability period after the appropriate dose from the reconstituted vial is diluted into the infusion solution.
o The 4-hour stability period when reconstituted product diluted into the infusion bag is stored at 2°C to 8°C does not include the time required for reconstitution or the 90-minute infusion time.
o The diluted infusion solution must be immediately infused for the 90-minute infusion time following the up to 4-hour stability period.
•     Calculate the volume of reconstituted Vyxeos liposomal required using the following formula: [volume required (mL) = dose of daunorubicin (mg/m2) x patient’s BSA (m2)/2.2 (mg/mL)].
The concentration of the reconstituted solution is 44 mg/20 mL (2.2 mg/mL) daunorubicin and 100 mg/20 mL (5 mg/mL) cytarabine.
•     Gently invert each vial 5 times prior to withdrawing the concentrate for dilution.
•     Aseptically withdraw the calculated volume of reconstituted Vyxeos liposomal from the vial(s) with a sterile syringe and transfer it to an infusion bag containing 500 mL of sodium chloride 9 mg/mL (0.9%) solution for injection, or 5% glucose. There may be residual product remaining in the vial. Discard unused portion.
•     Gently invert the bag to mix the solution. The dilution of the reconstituted product results in a deep purple, translucent, homogeneous dispersion.
•     If the diluted infusion solution is not used immediately, store in a refrigerator (2°C to 8°C) for up to 4 hours.
•     Gently invert the bag to mix the solution after refrigeration.

Administration instructions
•    Do not mix Vyxeos liposomal with, or administer as an infusion with, other medicinal products.
•    Administer Vyxeos liposomal by constant intravenous infusion over 90 minutes via an infusion pump through a central venous catheter or a peripherally inserted central catheter. An in-line membrane filter may be used for the intravenous infusion of Vyxeos liposomal, provided the minimum pore diameter of the filter is greater than or equal to 15 µm.
•    Flush the line after administration with sodium chloride 9 mg/mL (0.9%) solution for injection.

This medicinal product could have potential risk for the environment due to the cytotoxic and antimitotic activities, which could induce possible reproductive effects. All materials used for dilution and administration should be disposed of according to local procedures applicable to the discarding of antineoplastic agents. Any unused medicinal product or waste material should be disposed of in accordance with local requirements for cytotoxic agents.