Pharmaceutical particulars : מידע רוקחי

6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Hydroxy propyl beta cyclodextrine (hydroxypropylbetadex)
Sodium chloride
Hydrochloric acid (for pH adjustment)

6.2   Incompatibilities

Vortimal must not be infused into the same line or cannula concomitantly with other intravenous products. The bag should be checked to ensure that the infusion is complete.
When the Vortimal infusion is complete, the line may be used for administration of other intravenous products.


Blood products and short-term infusion of concentrated solutions of electrolytes: Electrolyte disturbances such as hypokalemia, hypomagnesemia and hypocalcemia should be corrected prior to initiation of voriconazole therapy (see sections 4.2 and 4.4). Vortimal must not be administered simultaneously with any blood product or any short-term infusion of concentrated solutions of electrolytes, even if the two infusions are running in separate lines.


Total parenteral nutrition: Total parenteral nutrition (TPN) need not be discontinued when prescribed with Vortimal but does need to be infused through a separate line. If infused through a multiple-lumen catheter, TPN needs to be administered using a different port from the one used for Vortimal. Vortimal must not be diluted with 4.2% Sodium Bicarbonate Infusion. Compatibility with other concentrations is unknown.
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

6.3 Shelf life
Unopened vial: The expiry date of the product is indicated on the packaging materials.

Reconstituted solution:. From a microbiological point of view, once reconstituted, the product must 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 2ºC to 8ºC (in a refrigerator), unless reconstitution/dilution has taken place in controlled and validated aseptic conditions.
Chemical and physical in-use stability has been demonstrated at 15-25ºC (room temperature) and at 2-8ºC (refrigerator) for 72 hours.
6.4 Special precautions for storage
The unreconstituted vial should be stored below 25ºC.
Store in the original carton box to protect from light.
For storage conditions after reconstitution of the medicinal product, see section 6.3.

6.5   Nature and contents of container

Type I clear glass vial of 25 ml sealed with a rubber stopper and an aluminium cap with plastic sub-cap.
6.6   Special precautions for disposal and other handling


The powder is reconstituted with either 19 ml of water for injections or 19 ml of 9 mg/ml (0.9%) Sodium Chloride for Infusion to obtain an extractable volume of 20 ml of clear concentrate containing 10 mg/ml of voriconazole. Discard the Vortimal vial if vacuum does not pull the diluent into the vial. It is recommended that a standard 20 ml (non-automated) syringe be used to ensure that the exact amount (19.0 ml) of water for injections or (9 mg/ml [0.9%]) Sodium Chloride for Infusion is dispensed. This medicinal product is for single use only and any unused solution should be discarded. Only clear solutions without particles should be used.


For administration, the required volume of the reconstituted concentrate is added to a recommended compatible infusion solution (detailed in the table below) to obtain a final voriconazole solution containing 0.5-5 mg/mL.



Required Volumes of 10 mg/ml Vortimal Concentrate
Volume of Vortimal Concentrate (10 mg/mL) required for:
Body Weight (kg)        3 mg/kg dose         4 mg/kg dose           6 mg/kg dose       8mg/kg dose     9 mg/kg (number of vials)    (number of vials)      (number of vials)     (number of       dose vials)    (number of vials)
10                     -                 4.0mL (1)                 -            8.0 mL (1)    9.0 mL (1) 15                     -                 6.0mL (1)                 -            12.0 mL (1)   13.5 mL (1)          20                     -                 8.0mL (1)                 -            16.0 mL (1)   18.0 mL (1)
25                     -                10.0mL (1)                 -            20.0 mL (1)   22.5 mL (2)
30                9.0 mL (1)             12 mL (1)             18 mL (1)        24.0 mL (2)   27.0 mL (2) 35                10.5 mL (1)            14 mL (1)             21 mL (2)        28.0 mL (2)   31.5 mL (2)          40                12.0 mL (1)            16 mL (1)             24 mL (2)        32.0 mL (2)   36.0 mL (2)
45                13.5 mL (1)            18 mL (1)             27 mL (2)        36.0 mL (2)   40.5 mL (3)
50                15.0 mL (1)            20 mL (1)             30 mL (2)        40.0 mL (2)   45.0 mL (3) 55                16.5 mL (1)            22 mL (2)             33 mL (2)        44.0 mL (3)   49.5 mL (3) 60                18.0 mL (1)            24 mL (2)             36 mL (2)        48.0 mL (3)   54.0 mL (3) 65                19.5 mL (1)            26 mL (2)             39 mL (2)        52.0 mL (3)   58.5 mL (3) 70                21.0 mL (2)            28 mL (2)             42 mL (3)             -             - 75                22.5 mL (2)            30 mL (2)             45 mL (3)             -             - 80                24.0 mL (2)            32 mL (2)             48 mL (3)             -             - 85                25.5 mL (2)            34 mL (2)             51 mL (3)             -             - 90                27.0 mL (2)            36 mL (2)             54 mL (3)             -             - 

95              28.5 mL (2)             38 mL (2)           57 mL (3)             -     - 100              30.0 mL (2)             40 mL (2)           60 mL (3)             -     - 
The reconstituted solution can be diluted with:

Sodium Chloride 9 mg/ml (0.9 %) Solution for Injection
Compound Sodium Lactate Intravenous Infusion
5% Glucose and Lactated Ringer’s Intravenous Infusion
5 % Glucose and 0.45 % Sodium Chloride Intravenous Infusion
5 % Glucose Intravenous Infusion
5 % Glucose in 20 mEq Potassium Chloride Intravenous Infusion
0.45 % Sodium Chloride Intravenous Infusion
5 % Glucose and 0.9 % Sodium Chloride Intravenous Infusion
The compatibility of voriconazole with diluents other than described above or in section 6.2 is unknown.