Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Sandoz Ltd, Frimley Business Park, Frimley, Camberley, Surrey, GU16 7SR, UK
Oxaliplatin in combination with 5-fluorouracil (5-FU) and folinic acid (FA) is indicated for:
The preparation of injectable solutions of cytotoxic agents must be carried out by trained specialist personnel with knowledge of the medical product used, in conditions that guarantee the integrity of the medical 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 (see section 6.6 for detailed information).
FOR ADULTS ONLY
The recommended dose for oxaliplatin in adjuvant setting is 85 mg/m² intravenously repeated every two weeks for 12 cycles (6 months).
The recommended dose for oxaliplatin in treatment of metastatic colorectal cancer is 85 mg/m² intravenously repeated every 2 weeks.
Dosage given should be adjusted according to tolerability (see section 4.4).
Oxaliplatin should always be administered before fluoropyrimidines-i.e. 5-fluorouracil (5FU).
Oxaliplatin is administered as a 2- to 6-hour intravenous infusion in 250 to 500 ml of 5% glucose solution (50mg/ml) to give a concentration between 0.2 mg/ml and 0.70 mg/ml; 0.7 mg/ml is the highest concentration in clinical practice for an oxaliplatin dose of 85 mg/m².
Oxaliplatin was mainly used in combination with continuous infusion 5-fluorouracil based regimens. For the two-weekly treatment schedule 5-fluorouracil regimens combining bolus and continuous infusion were used.
Oxaliplatin has not been studied in patients with severe renal impairment (see section 4.3).
In patients with moderate renal impairment, treatment may be initiated at the normally recommended dose (see section 4.4).
There is no need for dose adjustment in patients with mild renal dysfunction.
In a phase I study including patients with several levels of hepatic impairment, frequency and severity of hepato-biliary disorders appeared to be related to progressive disease and impaired liver function tests at baseline. No specific dose adjustment for patients with abnormal liver function tests was performed during clinical development.
No increase in severe toxicities was observed when oxaliplatin was used as a single agent or in combination with 5-fluorouracil in patients over the age of 65. In consequence no specific dose adaptation is required for elderly patients.
There is no relevant indication for use of oxaliplatin in children. The effectiveness of oxaliplatin single agent in the paediatric populations with solid tumors has not been established (see section 5.1).
Oxaliplatin is administered by intravenous infusion.
The administration of oxaliplatin does not require hyperhydration.
Oxaliplatin diluted in 250 to 500 ml of 5% glucose solution to give a concentration not less than 0.2 mg/ml must be infused via a central venous line or peripheral vein over 2 to 6 hours. Oxaliplatin infusion should always precede that of 5-fluorouracil.
In the event of extravasation, administration must be discontinued immediately.
Oxaliplatin must be further diluted before use. Only 5% glucose diluent is to be used to dilute the concentrate for solution for infusion (see section 6.6).
There is no known antidote to oxaliplatin. In cases of overdose, exacerbation of adverse events can be expected. Monitoring of haematological parameters should be initiated and symptomatic treatment given.
Medicinal product as packaged for sale: 24 months.
In-use stability after dilution: From a microbiological point of view, the product 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 to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.
Chemical and physical in-use stability has been demonstrated for 48 hours at 2 to 8°C when diluted to the concentrations of 0.2 mg/ml and 2.0 mg/ml with glucose 5% as well as for 6 hours at 20-25°C when diluted to the concentration of 0.2 mg/ml and 2.0 mg/ml with glucose 5%.
Keep the vial in the outer carton in order to protect from light.
Do not freeze.
Do not store above 25°C.
For storage conditions of the diluted medicinal product, see section 6.3.
Colourless glass vials with grey Halobutyl rubber stoppers and aluminium seals with plastic flip-off caps, with or without a protective plastic overwrap (Onco-Safe).
Pack sizes:
50mg/10ml: 1 vial, 5 vials, 10 vials
100mg/20ml: 1 vial
150mg/30ml: 1 vial
200mg/40ml: 1 vial
250mg/50ml: 1 vial
Not all pack sizes may be marketed.
As with other potentially toxic compounds, caution should be exercised when handling and preparing oxaliplatin solutions.
The handling of this cytotoxic agent by healthcare 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 solution for infusion should come into contact with skin, wash immediately and thoroughly with water.
If oxaliplatin concentrate or solution for infusion should come into contact with mucous membranes, wash immediately and thoroughly with water.
Oxaliplatin 85mg/m² IV infusion in 250 to 500 ml of 5% glucose solution 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 two 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.
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.
Inspect visually prior to use. Only clear solutions free from visible particles should be used.
This medicinal product is for single use only. Any unused concentrate should be discarded.
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 not less than 0.2 mg/ml.
Administer by IV infusion.
From a microbiological point of view, the product 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.
Chemical and physical in-use stability has been demonstrated for 48 hours at 2 to 8°C when diluted to the concentrations of 0.2 mg/ml and 2.0 mg/ml with glucose 5% as well as for 6 hours at 20-25 °C when diluted to the concentration of 0.2 mg/ml and 2.0 mg/ml with glucose 5%.
Inspect visually prior to use. Only clear solutions free from visible particles should be used.
The medicinal product is for single use only. Any unused infusion solution should be discarded (see chapter “disposal” below).
NEVER use sodium chloride solution for either reconstitution or dilution.
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 must precede the administration of 5-fluorouracil.
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 and in accordance with local requirements related to the disposal of hazardous waste.
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