Pharmaceutical particulars : מידע רוקחי

6.    PHARMACEUTICAL PARTICULARS
6.1   List of excipients

Myocet doxorubicin HCl
• lactose

Myocet liposomes
• egg phosphatidylcholine
•     cholesterol
•     citric acid
•     sodium hydroxide
•     water for injections 
Myocet buffer
• sodium carbonate
• water for injections

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

18 months
Chemical and physical in-use stability after reconstitution has been demonstrated for up to 8 hours at 25°C, and for up to 5 days at 2°C – 8C.

From a microbiological point of view, the medicinal product should be used immediately. 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C – 8C, unless reconstitution and dilution has taken place in controlled and validated aseptic conditions.

6.4     Special precautions for storage

Store in a refrigerator (2ºC – 8ºC).
For storage conditions after reconstitution of the medicinal product, see section 6.3.

6.5     Nature and contents of container

Myocet is available in cartons containing 1 set or 2 sets of the three constituents. Not all pack-sizes may be marketed.

Myocet doxorubicin HCl
Type I glass vials sealed with grey butyl rubber stoppers and orange flip-off aluminium seals, containing 50 mg of doxorubicin HCl lyophilised powder.

Myocet liposomes
Type I flint glass tubing vials sealed with siliconised grey stopper and green flip-off aluminium seals, containing not less than 1.9 ml of liposomes.

Myocet buffer
Glass vials sealed with siliconised grey stopper and blue aluminium flip-off seals, containing not less than 3 ml of buffer.

6.6     Special precautions for disposal and other handling

Preparation of Myocet
Aseptic technique must be strictly observed throughout handling of Myocet since no preservative is present.

Caution should be exercised in the handling and preparation of Myocet. The use of gloves is required 

Step 1. Set up
Two alternative heating methods can be used : a Techne DB-3 Dri Block heater or a water bath:
• Turn on the Techne DB-3 Dri Block heater and set the controller to 75°C-76°C. Verify the temperature set point by checking the thermometer(s) on each heat block insert.
• If using a water bath, turn on the water bath and allow it to equilibrate at 58°C (55°C-60°C).
Verify the temperature set point by checking the thermometer.

(Please note that whilst the control settings on the water bath and heat block are set to different levels the temperature of the vial contents are in the same range (55°C-60°C)).

Remove the carton of Myocet constituents from the refrigerator.

Step 2. Reconstitute doxorubicin HCl
• Withdraw 20 ml sodium chloride solution for injection (0.9%), preservative free (not provided in the package), and inject into each Myocet doxorubicin HCl, intended for preparation.
• Shake well in the inverted position to ensure doxorubicin is fully dissolved.

Step 3. Heat in water bath or dry heat block
• Heat the reconstituted Myocet doxorubicin HCl vial in the Techne DB-3 Dri Block heater with the thermometer in the block reading (75°C-76°C) for 10 minutes (not to exceed 15 minutes). If using the water bath heat the Myocet doxorubicin HCl vial with the thermometer temperature reading 55°C-60°C for 10 minutes (not to exceed 15 minutes).
• While heating proceed to step 4 
Step 4. Adjust Ph of liposomes
• Withdraw 1.9 ml of Myocet liposomes. Inject into Myocet buffer vial to adjust the Ph of liposomes. Pressure build-up may require venting.
• Shake well.

Step 5. Add Ph-adjusted liposomes to doxorubicin
• Using syringe, withdraw the entire vial contents of Ph-adjusted liposomes from the Myocet buffer vial.
• Remove the reconstituted Myocet doxorubicin HCl vial from the water bath or dry heat block.
SHAKE VIGOROUSLY. Carefully insert a pressure-venting device equipped with a hydrophobic filter. Then IMMEDIATELY (within 2 minutes) inject Ph-adjusted liposomes into vial of heated reconstituted Myocet doxorubicin HCl. Remove venting device.
• SHAKE VIGOROUSLY.
• WAIT for a minimum of 10 MINUTES before using, keeping the medicine at room temperature.

•   The Techne DB-3 Dri Block Heater is fully validated for use in the constitution of Myocet. Three inserts, each with two 43.7mm openings per insert must be used. To ensure correct temperature control the use of a 35mm immersion thermometer is recommended.

The resulting reconstituted preparation of Myocet contains 50 mg of doxorubicin HCl/25 ml of liposomal dispersion (2 mg/ml).

After reconstitution the finished product must be further diluted in 0.9% (w/v) sodium chloride for injection, or 5% (w/v) glucose solution for injection to a final volume of 40 ml to 120 ml per 50 mg reconstituted Myocet so that a final concentration of 0.4 mg/ml to 1.2 mg/ml doxorubicin is obtained.
Once constituted, the liposomal dispersion for infusion containing liposome-encapsulated doxorubicin should be a red orange opaque homogeneous dispersion. All parenteral solutions should be inspected visually for particulate matter and discoloration prior to administration. Do not use the preparation if foreign particulate matter is present.

Procedure for proper disposal

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.