Pharmaceutical particulars : מידע רוקחי

6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients

Lactose monohydrate

6.2 Incompatibilities
• DO NOT use in association with alkaline drugs or solutions (in particular 5-fluorouracil, basic solutions, trometamol and folinic acid products containing trometamol as an excipient).
• DO NOT reconstitute or dilute for infusion with saline solution.
• DO NOT mix with other drugs in the same infusion bag or infusion line (see Section 6.6:” Instructions concerning simultaneous administration with folinic acid).
• DO NOT use injection equipment containing aluminium

6.3 Shelf-life

Medicinal product as packaged for sale: 3 years
Reconstituted solution in the original vial:
From a microbiological and chemical point of view, the reconstituted solution should be diluted immediately.
Infusion preparation:
Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C to 8°C.
From a microbiological point of view, the infusion preparation 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 to 8°C unless dilution has taken place in controlled and validated aseptic conditions.

6.4 Special precautions for storage

Medicinal product as packaged for sale: no special storage conditions are required Reconstituted solution: should be diluted immediately.

Infusion preparation: store at 2°C to 8°C for not longer than 24 hours.
Inspect visually prior to use. Only clear solutions without particles should be used.
The medicinal product is for single use only. Any unused solution should be discarded.

6.5 Nature and contents of container
Glass vials with stoppers of chlorobutyl elastomer.
6.6 Instructions for use/handling
As with other potentially toxic compounds, caution should be exercised when handling and preparing oxaliplatin solutions.
Instructions for Handling
The handling of this cytotoxic agent by nursing or medical personnel requires every precaution to guarantee the protection of the handler and his surroundings.

The preparation of injectable solutions of cytotoxic agents must be carried out by trained specialist personnel with knowledge of the medicines used, in conditions that guarantee the protection of the environment and in particular the protection of the personnel handling the medicines. It requires a preparation area reserved for this purpose. It is forbidden to smoke, eat or drink in this area.

Personnel must be provided with appropriate handling materials, notably long sleeved gowns, protection masks, caps, protective goggles, sterile single-use gloves, protective covers for the work area, containers and collection bags for waste.
Excreta and vomit must be handled with care.
Pregnant women must be warned to avoid handling cytotoxic agents.
Any broken container must be treated with the same precautions and considered as contaminated waste.
Contaminated waste should be incinerated in suitably labelled rigid containers. (See section 6.6:”Instructions for use/handling”)

If oxaliplatin concentrate, reconstituted solution or infusion solution, should come into contact with skin, wash immediately and thoroughly with water.

If oxaliplatin concentrate, premix solution or infusion solution, should come into contact with mucous membranes, wash immediately and thoroughly with water.


Special precautions for administration
•   DO NOT use injection material containing aluminum.
•   DO NOT administer undiluted.

•   DO NOT reconstitute or dilute for infusion with saline solution.
•   DO NOT mix with any other medication in the same infusion bag or administer simultaneously by the same infusion line (in particular 5-fluorouracil, basic solutions, trometamol and folinic acid products containing trometamol as an excipient)

Oxaliplatin can be co-administered with folinic acid infusion using a Y-line placed immediately before the site of injection. The drugs should not be combined in the same infusion bag. Folinic acid must be diluted using isotonic infusion solutions such as 5 % glucose solution but NOT sodium chloride solutions or alkaline solutions.

Flush the line after oxaliplatin administration.
• USE ONLY the recommended solvents (see below).
• Any reconstituted solution that shows evidence of precipitation should not be used and should be destroyed with due regard to legal requirements for disposal of hazardous waste (see below).


Reconstitution of the solution
• Water for injections or 5 % glucose solution should be used to reconstitute the solution.
• For a vial of 50 mg: add 10 ml of solvent to obtain a concentration of 5 mg oxaliplatin/ml.
• For a vial of 100 mg: add 20 ml of solvent to obtain a concentration of 5 mg oxaliplatin/ml.

From a microbiological and chemical point of view, the reconstituted solution should be diluted immediately with 5 % glucose solution.
Inspect visually prior to use. Only clear solutions without particles should be used.
The medicinal product is for single use only. Any unused solution should be discarded.

Dilution before infusion

Withdraw the required amount of reconstituted solution from the vial(s) and then dilute with 250 ml to 500 ml of a 5 % glucose solution to give an oxaliplatin concentration not less than 0.2 mg/ml and 0.7 mg/ml. The concentration range over which the physico-chemical stability of oxaliplatin has been demonstrated is 0.2 mg/ml to 1.0 mg/ml 1.
Administer by IV infusion.
Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C to 8°C.
From a microbiological point of view, this infusion preparation 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 to 8°C unless dilution has taken place in controlled and validated aseptic conditions.
Inspect visually prior to use. Only clear solutions without particles should be used.
The medicinal product is for single use only. Any unused solution should be discarded.
NEVER use sodium chloride solution for either reconstitution or dilution.

Infusion
The administration of oxaliplatin does not require prehydration.
Oxaliplatin diluted in 250 to 500 ml of a 5 % glucose solution to give a concentration not less than 0.2 mg/ml must be infused either by peripheral vein or central venous line over 2 to 6 hours. When oxaliplatin is administered with 5-fluorouracil, the oxaliplatin infusion should precede that of 5-fluorouracil.


Disposal
Remnants of the medicinal product as well as all materials that have been used for reconstitution, for dilution and administration must be destroyed according to hospital standard procedures applicable to cytotoxic agents with due regard to current laws related to the disposal of hazardous waste.


6.7 Manufacturer
EBEWE Pharma Ges.m.b.H., A-4866 Unterach, Austria
6.8 Importer & License Holder`

Pharmalogic LTD, P.O.B. 3838, Petah-Tikva 49130