Pharmaceutical particulars : מידע רוקחי

6.      PHARMACEUTICAL PARTICULARS
6.1     List of excipients

Lactose monohydrate.

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

Medicinal product as packaged for sale:
The expiry date of the product is indicated on the packaging materials.
Reconstituted concentrate solution in the original vial:
The reconstituted concentrate solution should be diluted immediately.

Solution for infusion after dilution:
After dilution of the reconstituted solution in 5 % glucose solution, 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 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°C to 8°C.

6.4      Special precautions for storage

Medicinal product as packaged for sale: Store below 25°C.
For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.

6.5      Nature and contents of container

Type I glass vials with stoppers of chlorobutyl elastomer.
Supplied in packs of 1 vial containing oxaliplatin 50 mg or 100 mg.
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 product, 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 powder, reconstituted solution or infusion solution should come into contact with skin, wash immediately and thoroughly with water.

If oxaliplatin powder, reconstituted 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 aluminium.
-   DO NOT administer undiluted.
-   Only glucose 5% infusion solution (50 mg/ml) is to be used as a diluent.
-   DO NOT reconstitute or 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.

Instruction for use with folinic acid (as calcium folinate or disodium folinate) 
Oxaliplatin 85mg/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.

Instruction 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.

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 powder

-   Water for injections or 5 % glucose solution (50 mg/ml) 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.
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 (see below “Disposal”).

Dilution before infusion

Withdraw the required amount of reconstituted concentrate solution from the vial(s) and then dilute with 250 ml to 500 ml of a 5 % glucose solution to give an oxaliplatin concentration between not less than
0.2 mg/ml and 0.7 mg/ml, concentration range for which the physico-chemical stability of oxaliplatin has been demonstrated.
Administer by IV infusion.
After dilution in 5% glucose, 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.
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.
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 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.


7. MANUFACTURER medac Gesellschaft für klinische Spezialpräparate mbH
Wedel, Germany.