Pharmaceutical particulars : מידע רוקחי

6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients

VFEND powder for solution for infusion:
Sulphobutylether Beta Cyclodextrin Sodium (SBECD)
Water for Injections

VFEND film coated tablets:
Tablet Core:
Lactose Monohydrate
Pregelatinised Starch
Croscarmellose Sodium
Povidone
Magnesium Stearate

Film Coat:
Hypromellose
Titanium Dioxide
Lactose Monohydrate
Glycerol Triacetate

VFEND powder for oral suspension:
Sucrose
Citric Acid Anhydrous
Natural Orange Flavour
Sodium Citrate Dihydrate
Sodium Benzoate
Xanthan Gum
Silica Colloidal anhydrous
Titanium Dioxide
6.2 Incompatibilities

VFEND powder for solution for infusion:
VFEND 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 VFEND 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 hypokalaemia, hypomagnesaemia and hypocalcaemia should be corrected prior to initiation of voriconazole therapy (see sections 4.2 and 4.4). VFEND 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 VFEND 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 VFEND. VFEND 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.

VFEND film-coated tablets:
Not applicable

VFEND Powder for oral suspension:
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

6.3 Shelf life

VFEND powder for solution for infusion:
The expiry date of the product is indicated on the packaging materials.
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 2°C to 8°C (in a refrigerator), unless reconstitution has taken place in controlled and validated aseptic conditions.

Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C to 8°C.

VFEND film-coated tablets:
The expiry date of the product is indicated on the packaging materials.
VFEND powder for oral suspension:
The expiry date of the product is indicated on the packaging materials.
The shelf life of the constituted oral suspension is 14 days at a temperature below 30°C, do not refrigerate or freeze.

6.4 Special precautions for storage

VFEND powder for solution for infusion:
The unreconstituted vial should be stored below 30ºC.
For storage conditions after reconstitution of the medicinal product, see section 6.3.
VFEND film-coated tablets:
Store below 30°C.

VFEND powder for oral suspension:
Store at 2°C- 8°C (in a refrigerator) before constitution.
For storage conditions after constitution, see section 6.3.
Keep the container tightly closed.

6.5 Nature and contents of container
VFEND powder for solution for infusion:
Sterile lyophilised powder in single use 30 mL clear Type I glass vial.

Film-coated tablets:
PVC / Aluminium blister in cartons of 2, 10, 14, 20, 28, 30, 50, 56 and 100.
Not all pack sizes may be marketed.

VFEND powder for oral suspension:
One 100ml high-density polyethylene (HDPE) bottle (with polypropylene child resistant closure) containing 45g of powder for oral suspension. A measuring cup (graduated to indicate 23ml), 5ml oral syringe and a press-in bottle adaptor are also provided.

6.6   Special precautions for disposal and other handling

VFEND powder for solution for infusion:
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 VFEND 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 VFEND Concentrate

Volume of VFEND Concentrate (10 mg/mL) required for:

Body Weight         3 mg/kg dose         4 mg/kg dose       6 mg/kg dose        8mg/kg       9 mg/kg (kg)              (number of           (number of         (number of           dose         dose vials)               vials)             vials)         (number       (number of vials)    of vials)
10                    -              4.0mL (1)                -            8.0 mL        9.0 mL (1)          (1)
15                    -              6.0mL (1)                -           12.0 mL       13.5 mL (1)          (1)
20                    -              8.0mL (1)                -           16.0 mL       18.0 mL
(1)          (1)
25                    -              10.0mL (1)               -           20.0 mL       22.5 mL
(1)          (2)
30               9.0 mL (1)          12 mL (1)           18 mL (1)        24.0 mL       27.0 mL (2)          (2)
35              10.5 mL (1)          14 mL (1)           21 mL (2)        28.0 mL       31.5 mL (2)          (2)
40              12.0 mL (1)          16 mL (1)           24 mL (2)        32.0 mL       36.0 mL
(2)          (2)
45              13.5 mL (1)          18 mL (1)           27 mL (2)        36.0 mL       40.5 mL
(2)          (3)
50              15.0 mL (1)          20 mL (1)           30 mL (2)        40.0 mL       45.0 mL (2)          (3)
55              16.5 mL (1)          22 mL (2)           33 mL (2)        44.0 mL       49.5 mL (3)          (3)
60              18.0 mL (1)          24 mL (2)           36 mL (2)        48.0 mL       54.0 mL (3)          (3)
65              19.5 mL (1)          26 mL (2)           39 mL (2)        52.0 mL       58.5 mL (3)          (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.

VFEND film-coated tablets:
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

VFEND powder for oral suspension:
Constitution instructions:
1. Tap the bottle to release the powder.
2. Add 2 measuring cups of water, providing a total volume of 46 ml.
3. Shake the closed bottle vigorously for about 1 minute.
4. Remove child-resistant cap. Press bottle adaptor into the neck of the bottle.
5. Replace the cap.
6. Write the date of expiration of the constituted suspension on the bottle label (the shelf life of the constituted oral suspension is 14 days).

Following constitution, the volume of the oral suspension is 75ml, providing a usable volume of 70ml.

Instructions for use:
Shake the closed bottle of constituted suspension for approximately 10 seconds before each use.
Once constituted, VFEND oral suspension should only be administered using the oral syringe supplied with each pack. Refer to the patient leaflet for more detailed instructions for use.

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