Pharmaceutical particulars : מידע רוקחי

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients
Water for injection.

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 coadministered with folinic acid via a Y-line.

- DO NOT mix with alkaline drugs or solutions, in particular 5-fluorouracil, folinic acid preparations containing trometamol as an excipient and trometamol salts of other drugs. Alkaline drugs 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 drugs in the same infusion bag or infusion line (see section6.6 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% dextrose, chemical and physical in-use stability has been demonstrated for 48 hours at +2°C to +8°C and for 8 hours at <25°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

Keep the vial in the original packaging to protect from light.

Do not store above +300C. Do not freeze.
6.5 Nature and contents of container

1 vial with 10 ml concentrate (Type I clear glass) with bromobutyl elastomer stopper and aluminum cap 
1 vial with 20 ml concentrate (Type I clear glass) with bromobutyl elastomer stopper and aluminum cap 
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 medicines used, in conditions that guarantee the integrity of the product, the protection of the environment and in particular the protection of the personnel handling the medicines, 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 dextrose 5% infusion solution is to be used as a diluent. DO NOT dilute for infusion with sodium chloride or chloride containing solutions.
- 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 drugs or solutions, in particular 5-fluorouracil, folinic acid preparations containing trometamol as an excipient and trometamol salts of other drugs. Alkaline drugs 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 to 500 ml of 5% dextrose solution is given at the same time as folinic acid IV infusion in 5% dextrose solution, over 2 to 6 hours, using a Y-line placed immediately before the site of infusion. These two drugs 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% dextrose 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.

Instructions for use in combined therapy of oxaliplatin with leucovorin, irinotecan and 5-fluorouracil (FOLFIRINOX)

Oxaliplatin 85 mg/m2 given as a 2-hour intravenous infusion, immediately followed by leucovorin (400 mg/m2, 2-hour intravenous infusion) with the addition after 30 minutes of irinotecan (180 mg/m2, 90- minute intravenous infusion through a Y-connector) and immediately followed by 5-fluorouracil (400 mg/m2 intravenous bolus followed by 2,400 mg/m2 continuous intravenous infusion for 46 hours), in 2- week cycles up to 6 months.

For additional information on drugs 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.
Dilution before infusion

Oxaliplatin is administered as a 2- to 6-hour intravenous infusion in 250 to 500 ml of 5% dextrose solution to give a concentration between 0.2 mg/ml and 0.7 mg/ml; 0.70 mg/ml is the highest concentration in clinical practice for an oxaliplatin dose of 85 mg/m2.

Withdraw the required amount of concentrate from the vial(s) and then dilute with 250 ml to 500 ml of a 5% dextrose solution to give an oxaliplatin concentration between 0.2 mg/ml and 2 mg/ml; concentration range for which the physico-chemical stability of oxaliplatin has been demonstrated.

Administer by IV infusion.
After dilution in 5% dextrose, chemical and physical in-use stability has been demonstrated for 48 hours at +2°C to +8°C and for 8 hours at <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°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 infusion solution should be discarded.

NEVER use sodium chloride 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 to 500 ml of a 5% dextrose 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.