Pharmaceutical particulars : מידע רוקחי

6.   PHARMACEUTICAL PARTICULARS

6.1     List of excipients
Sodium hydroxide, Water for injections.

6.2 Incompatibilities

Fluorouracil should only be diluted with normal saline or a 5 % glucose solution.
Fluorouracil should not be mixed with other substances in the same I.V. injection or infusion, as a precipitate may form.

Incompatibilities with following substances have been reported:
Cisplatin, cytarabine, doxorubicin, calcium folinate, methotrexate, vinorelbine, diazepam, droperidol, filgrastim, gallium nitrate, metoclopramide, morphine, ondansetron, parenteral nutrition solutions.


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

6.4 Special precautions for storage

Store below 25ºC. Do not refrigerate or freeze.
For single use only.
Only use clear and colourless to slightly yellowish solutions.
If a precipitate has formed as a result of exposure to low temperatures, redissolve by careful heating to 60°C accompanied by shaking. Allow to cool prior to use.

Shelf life after first opening
After first opening, can be used for 28 days at a temperature of 20 - 25°C.

Shelf life after dilution
Dilution can be done with 0.9% sodium chloride solution or 5% glucose solution. Stability data in concentrations of 0.35 mg/ml and 15 mg/ml have shown that the maximum shelf life of ready-made fluorouacil infusion solution is 28 days.

This shelf life refers both to refrigerator storage (2 - 8°C) including protection from light and storage at ambient temperature (20 - 25°C) with or without protection from light.

The prepared infusate demonstrated chemical and physical stability for 28 days. From a microbiological point of view, however, the product should be used immediately. If not used immediately, storage times and conditions of the prepared infusate prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 - 8°C, unless dilution has taken place under controlled and validated aseptic conditions.

6.5 Nature and contents of container

Glass vial containing 20ml
Glass vial containing 50ml
Glass vial containing 100ml
Type I amber glass vials with grey bromobutyl rubber stopper with aluminium crimp caps.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other instructions for handling 
Due to the possible mutagenic and carcinogenic effects, enhanced safety precautions for hospital staff and physicians apply. While handling fluorouacil any contact with skin and mucous membranes should be avoided. Failing this, immediately wash with soap and water.

In the event of contact with the eyes, the affected area should be washed with copious amounts of water, and medical attention should be sought. All provisions must be made to allow for absolutely aseptic work. The use of a workspace with laminar flow is recommended. Protective clothing must be worn while handling fluorouacil.

Pregnant staff must not work with Fluorouracil.

Inactivation:
700 °C
Sodium hypochlorite (liquor natrii hypochlorosi) diluted with 10 parts of water Concentrated NaOH over several hours.

The ready solution should be used immediately after preparation.
If a precipitate has formed as a result of exposure to low temperatures, redissolve by careful heating to 60°C accompanied by shaking. Allow to cool prior to use.

Loss of efficacy due to the adsorption of fluorouacil in the glass infusion container has been described in the literature.

The handling and disposal regulations for cytostatic agents must be met.

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

7.   LICENCE HOLDER AND MANUFACTURER