Pharmaceutical particulars : מידע רוקחי

6.      PHARMACEUTICAL PARTICULARS

6.1     List of excipients
Lactose monohydrate
Water for injections

6.2     Incompatibilities
The diluted medicinal product should not be mixed with other medications in the same infusion bag or infusion line. Under instructions for use described in section 6.6, oxaliplatin can be co-administered with folinic acid via a Y-line.


- DO NOT mix with alkaline medicinal agents or solutions, in particular 5-fluorouracil, folinic acid preparations containing trometamol as an excipient and trometamol salts of other medicinal products.
Alkaline medicinal agents or solutions will adversely affect the stability of oxaliplatin (see section 6.6).
- DO NOT dilute oxaliplatin with saline or other solutions containing chloride ions (including calcium, potassium or sodium chlorides).
- DO NOT mix with other medicinal products in the same infusion bag or infusion line (see section 6.6 for instructions concerning simultaneous administration with folinic acid).
- DO NOT use injection equipment containing aluminium.
6.3     Shelf life

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

After dilution in 5% glucose solution, chemical and physical in-use stability has been demonstrated for 24 hours at 2-8°C and for 6 hours when stored in ambient light at 15-25°C.
From a microbiological point of view, the solution for infusion 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 2-8°C unless dilution has taken place in controlled and validated aseptic conditions.


6.4     Special precautions for storage

Store below 25°C and keep the vial in the original package in order to protect from light.
For storage conditions of the diluted medicinal product, see section 6.3.

6.5     Nature and contents of container
Colourless, type I glass vial of 4 ml, 10 ml, 20 ml or 40 ml of concentrate with bromobutyl rubber stopper, aluminium seal and polypropylene snap-cap.
Pack sizes: packs with 1 vial containing 4 ml, 10 ml, 20 ml, or 40 ml of concentrate for solution for infusion.
Not all pack sizes may be marketed.

6.6     Special precautions for disposal and other 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 medicinal products used, in conditions that guarantee the integrity of the medicinal products, the protection of the environment and, in particular, the protection of the personnel handling the medicinal products, in accordance with the hospital policy. 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 below section “Disposal”.
If oxaliplatin concentrate or infusion solution should come into contact with skin, wash immediately and thoroughly with water.
If oxaliplatin concentrate or infusion solution should come into contact with mucous membranes, wash immediately and thoroughly with water.

Special precautions for administration
- DO NOT use injection equipment containing aluminium.
- DO NOT administer undiluted.
- ONLY glucose 5% infusion solution (50 mg/ml) is to be used as a diluent.
- DO NOT dilute for infusion with sodium chloride or chloride-containing solutions.
- DO NOT administer extravascularly.
- DO NOT mix with any other medication in the same infusion bag or administer simultaneously by the same infusion line.
- DO NOT mix with alkaline medicinal agents or solutions, in particular 5-fluorouracil, folinic acid preparations containing trometamol as an excipient and trometamol salts of other medicinal products. Alkaline medicinal agents or solutions will adversely affect the stability of oxaliplatin.


Instructions for use with folinic acid (as calcium folinate or disodium folinate) 
Oxaliplatin 85 mg/m2 IV infusion in 250 ml to 500 ml of 5% glucose solution (50 mg/ml) is given at the same time as folinic acid IV infusion in 5% glucose solution, over 2 to 6 hours, using a Y-line placed immediately before the site of infusion.
These 2 medicinal products should not be combined in the same infusion bag. Folinic acid must not contain trometamol as an excipient and must only be diluted using isotonic 5% glucose solution, never in alkaline solutions or sodium chloride or chloride-containing solutions.

Instructions for use with 5-fluorouracil
Oxaliplatin should always be administered before fluoropyrimidines - i.e., 5-fluorouracil.
After oxaliplatin administration, flush the line and then administer 5-fluorouracil.
For additional information on medicinal products combined with oxaliplatin, see the corresponding manufacturer’s summary of product characteristics.


Concentrate for solution for infusion
Inspect visually prior to use. Only clear solutions without particles should be used.
The medicinal product is for single use only. Any unused concentrate should be discarded (see below section “Disposal”).

Dilution before infusion
Withdraw the required amount of concentrate from the vial(s) and then dilute with 250 ml to 500 ml of a 5% glucose solution to give an oxaliplatin concentration between 0.2 mg/ml and 0.7 mg/ml. Physico-chemical stability of oxaliplatin has been demonstrated for a concentration range between 0.2 mg/ml and 2 mg/ml.
Administer by IV infusion.
After dilution in 5% glucose, chemical and physical in-use stability has been demonstrated for 24 hours at 2- 8°C and for 6 hours when stored in ambient light at 15-25°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 2-8°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 infusion solution should be discarded.
NEVER use sodium chloride solution or chloride-containing solutions for dilution.
The compatibility of oxaliplatin solution for infusion has been tested with representative, PVC-based administration sets.

Infusion
The administration of oxaliplatin does not require prehydration.
Oxaliplatin diluted in 250 ml 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 must precede the administration of 5-fluorouracil.

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



7.      LICENCE HOLDER AND MANUFACTURER

Teva Israel Ltd.,
124 Dvora HaNevi'a St., Tel Aviv 6944020.