Oxaliplatin, in combination with 5-fluorouracil (5FU) and folinic acid (FA), is indicated for:
• adjuvant treatment of stage III (Dukes’ C) colon cancer after complete resection of the primary tumor,
• treatment of metastatic colorectal cancer.

The preparation of injectable solutions of cytotoxic agents must always be carried out by trained specialist personnel with knowledge of the medicines used, in conditions ensuring drug integrity, the protection of the environment and in particular protection of the personnel handling the medicines, according to hospital practice. It requires a preparation area reserved for this purpose. It is forbidden to smoke, eat or drink in this area (see Section 6.6).
Posology
FOR USE IN ADULTS ONLY.
The recommended dose of oxaliplatin in the adjuvant setting is 85 mg/m² intravenously, repeated every 2 weeks for 12 cycles (6 months).
The recommended dose of oxaliplatin in the treatment of metastatic colorectal cancer is 85 mg/m² intravenously, repeated every two weeks.
The dose should be adjusted according to tolerability (see section 4.4).
Oxaliplatin should always be administered before fluoropyrimidines, i.e. before 5-fluorouracil.
Oxaliplatin is administered as a 2- to 6-hour intravenous infusion in 250 to 500 ml of 5% glucose solution (50 mg/ml) in order to obtain a concentration of between 0.2 mg/ml and 0.7 mg/ml; 0.7 mg/ml is equivalent to the highest concentration observed in clinical practice for an 85 mg/m2 dose of oxaliplatin.
Oxaliplatin was mostly administered in combination with continuous infusion of 5-fluorouracil. For the two-weekly treatment schedule, a 5-fluorouracil regimen with bolus and continuous infusion was used.
Populations at risk
Patients with renal insufficiency:
Oxaliplatin has not been studied in patients with severe renal insufficiency (see section 4.3).
In patients with moderate renal impairment, treatment can be initiated at the recommended dose (see section 4.4). There is no need for dose adjustment in patients with mild renal impairment.
Patients with hepatic insufficiency:

In a phase I study including patients with varying degrees of hepatic insufficiency, the frequency and severity of hepatobiliary disorders appeared to be related to progression of the disease and to initial liver function abnormalities. No specific dose adjustment was performed during clinical development for patients with impaired liver function.
Elderly subjects:
No increase in severe toxicities was observed when the drug was used as a single agent or in combination with 5-fluorouracil in patients over the age of 65. Therefore, no specific dose adjustment is required for elderly subjects.
Pediatric patients:
Oxaliplatin is not indicated for use in children. The efficacy of oxaliplatin administered alone in children with solid tumors has not been established (see section 5.1).
Method of administration
Oxaliplatin is administered by intravenous infusion.
The administration of oxaliplatin does not require hyperhydration.
Oxaliplatin diluted in 250-500 ml of 5% glucose solution (50 mg/ml) to obtain a concentration greater than 0.2 mg/ml, must be infused either via central venous line or into a peripheral vein over 2-6 hours. Oxaliplatin infusion must always be given before 5-fluorouracil.
In the event of extravasation, administration must be discontinued immediately.
Instructions for use
Oxaliplatin must be diluted before use. Only a 5% glucose solution (50 mg/ml) should be used to dilute the concentrate for solution (see section 6.6).

Oxaliplatin is contraindicated: • in patients with a history of hypersensitivity to oxaliplatin or to one of the excipients, • during breast-feeding, • in patients with bone marrow failure (neutrophils <2x109/l and/or platelet count <100x109/l) before the first treatment cycle, • in patients with peripheral sensory neuropathy with functional impairment before the first treatment cycle, • in patients with severe renal insufficiency (creatinine clearance <30 ml/min).

Oxaliplatin must only be used in departments specialized in administering cytotoxics and must be administered under the supervision of a physician qualified in the use of cancer chemotherapy agents.
Due to limited information on safety in patients with moderately impaired renal function, the benefit/risk ratio for the patient should be weighed before administration.
In these patients, renal function should be closely monitored and the dose adjusted based on toxicity.
Close clinical monitoring must be performed in patients with a history of allergic reactions to other platinum-containing compounds. If an anaphylactic-like reaction occurs, the infusion must be immediately discontinued and appropriate symptomatic treatment initiated. Oxaliplatin rechallenge is contraindicated in these patients.
In the event of extravasation, the infusion must be stopped immediately and usual local symptomatic treatment initiated.
Neurological toxicity of oxaliplatin must be carefully monitored, especially if co-administered with other medications with specific neurological toxicity. A neurological examination must be performed before each administration and periodically thereafter.
For patients who develop acute laryngopharyngeal dysesthesia (see section 4.8) during or within the hours following a two-hour infusion, subsequent oxaliplatin administration should be carried out over 6 hours.
If patients develop neurological symptoms (paresthesia, dysesthesia), the recommended oxaliplatin dose adjustments should be based on the duration and severity of these symptoms:
• if symptoms last longer than 7 days and are painful, the oxaliplatin dose for the following cycle should be reduced from 85 to 65 mg/m² (metastatic setting) or to 75 mg/m² (adjuvant setting),
• if paresthesia without functional impairment persists until the next cycle, the oxaliplatin dose should be reduced from 85 to 65 mg/m² (metastatic setting) or to 75 mg/m² (adjuvant setting),
• if paresthesia with functional impairment persists until the next cycle, oxaliplatin treatment should be discontinued,
• if symptoms improve following discontinuation of oxaliplatin therapy, resuming the treatment can be considered.

Patients should be informed that symptoms of peripheral sensory neuropathy may persist after the end of treatment. Moderate, localized paresthesia or paresthesia that may interfere with functional activities may persist for more than 3 years after stopping treatment in the adjuvant setting.
Gastrointestinal toxicity, such as nausea and vomiting, warrants prophylactic and/or curative antiemetic treatment (see section 4.8).
Severe diarrhea and/or vomiting may cause dehydration, paralytic ileus, intestinal occlusion, hypokalemia, metabolic acidosis and renal impairment, particularly when oxaliplatin is used in combination with 5-fluorouracil.
If hematological toxicity occurs (neutrophils <1.5x109/l or platelets <50x109/l), administration of the next cycle should be postponed until hematological values return to acceptable levels. A complete blood count must be performed before initiating oxaliplatin treatment and before each new cycle.
Patients must be informed of the risk of diarrhea/vomiting, mucositis/stomatitis and neutropenia after oxaliplatin and 5-fluorouracil administration, and must urgently contact their treating physician for appropriate care.
If mucositis/stomatitis occurs, with or without neutropenia, the next administration should be postponed until mucositis/stomatitis have returned to grade 1 or lower and/or until the neutrophil count is ≥ 1.5x109/l.
As oxaliplatin is combined with 5-fluorouracil (with or without folinic acid), the usual dose adjustments recommended for 5-fluorouracil-associated toxicities must be applied.
If grade 4 diarrhea, grade 3 or 4 neutropenia (neutrophils <1x109/l) or grade 3 or 4 thrombocytopenia (platelets <50x109/l) occur, the oxaliplatin dose must be reduced from 85 to 65 mg/m² (metastastic setting) or to 75 mg/m² (adjuvant setting), in addition to any 5-fluorouracil dose adjustment.
If unexplained respiratory symptoms such as non-productive cough, dyspnea, crepitant rale or radiologically visible pulmonary infiltrates occur, oxaliplatin treatment must be discontinued until lung examinations rule out interstitial lung disease (see section 4.8).
In the event of abnormal liver function test results or portal hypertension clearly not due to liver metastases, the possibility of very rare cases of liver vascular disorders induced by the drug should be considered.
Concerning use in pregnant women, see section 4.6.
Genotoxic effects have been observed with oxaliplatin in preclinical studies. Men are therefore advised not to father children during treatment with oxaliplatin and for 6 months following the end of treatment, and also to ask for advice about banking sperm before treatment, since oxaliplatin can cause irreversible infertility. Women must not become pregnant during oxaliplatin treatment and must use an effective method of contraception (see section 4.6).

In patients who have received a single dose of 85 mg/m² oxaliplatin immediately before administration of 5-fluorouracil, no change in exposure to 5-fluorouracil has been observed.
In vitro, no significant displacement of oxaliplatin plasma protein binding has been observed with the following agents: erythromycin, salicylates, granisetron, paclitaxel, and sodium valproate.

There is no information available to date on the safety of use of oxaliplatin in pregnant women. Reproduction toxicity has been observed in animal studies.
Oxaliplatin is therefore inadvisable during pregnancy and in women of child-bearing age who are not using contraception.
Oxaliplatin administration must only be considered after informing the patient specifically of the risk to the fetus and with her consent.
Appropriate contraceptive measures must be used during treatment and continued by female patients for 4 months, and by male patients for 6 months following the end of treatment.
Excretion in breast milk has not been studied. Breast-feeding is contraindicated during oxaliplatin treatment.
Oxaliplatin could have a negative effect on fertility (see section 4.4).

Effects on the ability to drive and use machines have not been studied. However, since oxaliplatin treatment causes an increased risk of dizziness, nausea, vomiting and other neurological symptoms affecting walking and balance, treatment may have a minor or moderate impact on the ability to drive and use machines. Vision disorders, in particular transient loss of sight (reversible upon treatment discontinuation) may affect the ability to drive and to use machines. Patients must therefore be warned of these possible effects on the ability to drive and use machines.

The most frequent adverse events observed with the oxaliplatin + 5-fluorouracil/folinic acid (5-FU/FA) combination are gastrointestinal (diarrhea, nausea, vomiting and mucositis), hematological (neutropenia, thrombocytopenia) and neurological (acute and dose-cumulative peripheral sensory neuropathy). Overall, these adverse events were more frequent and severe with the oxaliplatin + 5-FU/FA combination than with 5-FU/FA alone.
The incidences reported in the table below were obtained from clinical studies in the metastatic and adjuvant settings (including 416 and 1108 patients, respectively, in the oxaliplatin + 5-FU/FA treatment arm) and from post-marketing experience.
The incidences shown in the table are categorized using the following scale: very common ( 1/10), common ( 1/100, < 1/10), uncommon ( 1/1000, < 1/100), rare ( 1/10 000, < 1/1000), very rare (< 1/10 000), and not known (cannot be estimated from the available data).
Further details are given after the table.

Nervous system disorders
The dose-limiting toxicity of oxaliplatin is neurological. This mainly involves peripheral sensory neuropathy, characterized by dysesthesia and/or paresthesia of the extremities with or without cramps, often triggered by the cold. These symptoms occur in up to 95% of patients treated. The duration of these symptoms, which usually regress between treatment cycles, increases with the number of cycles.
Depending on the duration of symptoms, the onset of pain and/or functional impairment requires dose adjustment or even treatment discontinuation (see section 4.4).
This functional impairment, which includes difficulty performing precise movements, is a possible consequence of sensory damage. The risk of onset of persistent symptoms at a cumulative dose of 850 mg/m² (i.e. 10 cycles) is about 10%, and about 20% at a cumulative dose of 1 020 mg/m² (i.e. 12 cycles).
In most cases, neurological signs and symptoms improve or resolve completely when treatment is discontinued.
In the adjuvant treatment of colon cancer, 87% of patients have either no symptoms or only moderate symptoms 6 months after discontinuing treatment. After more than 3 years of follow-up, about 3% of patients have either persistent, localized paresthesia of moderate intensity (2.3%) or paresthesia that may interfere with functional activities (0.5%).
Acute neurosensory effects have been reported (see section 5.3). These symptoms appear within hours of administration and often occur on exposure to cold. The usual signs are transient paresthesia, dysesthesia or hypoesthesia. Acute laryngopharyngeal dysesthesia occurs in 1% - 2% of patients, and is characterized by subjective sensations of dysphagia or dyspnea/feeling of suffocation, with no objective signs of respiratory distress (with no cyanosis or hypoxia), or by laryngospasm or bronchospasm (with no stridor or wheezing).
Although antihistamines and bronchodilators have been administered in such cases, these symptoms are rapidly reversible, even if no treatment is given. Extending the infusion time during subsequent cycles helps to reduce the incidence of this syndrome (see section 4.4).
Other symptoms have occasionally been observed: jaw spasm, muscle spasm, involuntary muscle contractions, myoclonus, coordination disorders, abnormal gait, ataxia, balance disorders, constriction of the throat or chest, oppression, discomfort, and pain. Furthermore, cranial nerve damage may occur concomitantly or separately, such as palpebral ptosis, diplopia, aphonia, dysphonia, hoarseness, occasionally described as vocal cord paralysis, lingual dysesthesia or dysarthria occasionally described as aphasia, trigeminal neuralgia, facial or ocular pain, reduced visual acuity, visual field disturbances.
Other neurological symptoms, such as dysarthria, loss of tendon reflexes and Lhermitte's sign have been reported during treatment with oxaliplatin. Isolated cases of optic neuritis have been reported.
Post-marketing experience: seizures of unknown incidence.

Prophylactic and/or curative treatment with potent anti-emetic agents is indicated.
Severe diarrhea and/or vomiting may result in dehydration, paralytic ileus, intestinal obstruction, hypokalemia, metabolic acidosis and renal impairment, particularly when oxaliplatin is combined with 5-fluorouracil (see section 4.4).
Hepatobiliary disorders
Very rare (≤ 1/10 000):
Hepatic sinusoidal obstruction syndrome, also known as hepatic veno-occlusive disease, or histological abnormalities related to this type of syndrome, including peliosis hepatis, nodular regenerative hyperplasia and perisinusoidal fibrosis. The clinical signs may be portal hypertension and/or elevated transaminases.
Renal and urinary disorders
Very rare (≤ 1/10 000):
Acute tubular necrosis, acute interstitial nephritis resulting in acute renal failure.

There is no known antidote to oxaliplatin.
In the event of overdose, exacerbation of adverse effects can be expected. Monitoring of hematological parameters must be initiated, together with symptomatic treatment of other toxicities.

Pharmacotherapeutic group: other antineoplastic agents, platinum compounds.
ATC code: L01XA03
Oxaliplatin is an antineoplastic agent belonging to a new class of platinum compounds in which the platinum atom is complexed with 1,2-diaminocyclohexane ("DACH") and an oxalate group. Oxaliplatin is a single enantiomer, (SP-4-2)-[(1R,2R)-cyclohexane-1,2-diamine-kN, KN’] [ethanediato(2-)-kO1, KO2] platinum.
Oxaliplatin exhibits a wide spectrum of both in vitro cytotoxicity and in vivo antitumor activity in various tumor model systems, including human colorectal cancer models.
Oxaliplatin has also shown in vitro and in vivo efficacy in various cisplatin-resistant cell lines.
Synergistic cytotoxic activity with 5-fluorouracil has been demonstrated both in vitro and in vivo.
Studies on the mechanism of action, which has however not been completely elucidated, have shown that the aqua derivatives resulting from the biotransformation of oxaliplatin interact with DNA to form both intra- and inter-strand cross-links, resulting in interruption of DNA synthesis, which underlies the cytotoxic and antitumor effects.
In patients with metastatic colorectal cancer, the efficacy of oxaliplatin (85 mg/m2 repeated every two weeks) in combination with 5-fluorouracil/folinic acid (5-FU/FA) has been reported in three clinical studies:
• as first-line treatment, in a 2-arm, comparative, phase III study (EFC2962), 420 patients were randomized either to 5-FU/FA alone (LV5FU2, N=210) or to oxaliplatin+5-FU/FA (FOLFOX4, N=210);

• in pretreated patients, in a 3-arm, comparative, phase III study (EFC4584), 821 patients, refractory to the irinotecan (CPT-11) + 5-FU/FA combination, were randomized to 5-FU/FA alone (LV5FU2, N=275), to single-agent oxaliplatin (N=275), or to oxaliplatin+5-FU/FA (FOLFOX4, N=271);
• finally, in a non-controlled phase II study (EFC2964), patients refractory to 5-FU/FA alone were treated with the oxaliplatin+5-FU/FA combination (FOLFOX4, N=57).
In the two randomized clinical studies (EFC2962 as first-line treatment and EFC4584 in pretreated patients) a significantly superior response rate was demonstrated as well as longer progression-free survival (PFS)/time to progression (TTP) compared to treatment with 5-FU/FA alone.
In the EFC4584 study in refractory pretreated patients, the difference in median overall survival (OS) between oxaliplatin + 5-FU/FA combination and 5-FU/FA was not statistically significant.

Overall Survival (ITT analysis):
At the time of the 3-year disease-free survival analysis, which was the primary endpoint of the MOSAIC study, 85.1% of the patients were still alive in the FOLFOX4 arm versus 83.8% in the LV5FU2 arm. This showed an overall reduction in mortality risk of 10% in favor of FOLFOX4, not reaching statistical significance (hazard ratio = 0.90).
Results were 92.2% versus 92.4% in the stage II (Dukes’ B2) sub-group (hazard ratio = 1.01) and 80.4% versus 78.1% in the stage III (Dukes’ C) sub-group (hazard ratio = 0.87), for FOLFOX4 and LV5FU2, respectively.
Oxaliplatin single-agent therapy was studied in children in 2 phase I studies (69 patients) and in 2 phase II studies (90 patients). A total of 159 pediatric patients (age range: 7 months to 22 years) with solid tumors were treated. The efficacy of oxaliplatin administered alone was not established in the treated population.
Enrollment in these two phase II studies was stopped due to lack of tumor response.

The pharmacokinetics of the various active metabolites have not been determined. The table below indicates the pharmacokinetic parameters of ultrafiltered platinum, i.e. all the unbound, active and inactive species of platinum, following a two-hour infusion of oxaliplatin 130 mg/m² every three weeks for 1 to 5 cycles, and of oxaliplatin 85 mg/m² every two weeks for 1 to 3 cycles:

Following a 2-hour infusion, 15% of administered platinum is found in the systemic circulation, the remaining 85% having been rapidly distributed into tissues or excreted in urine. Irreversible binding to red blood cells and plasma results in half-lives in these matrices that are close to the natural turnover of red blood cells and serum albumin. No accumulation of platinum was observed in plasma ultrafiltrate following an 85 mg/m2 infusion every 2 weeks or a 130 mg/m2 infusion every 3 weeks, and steady state was reached in cycle 1 in this matrix. Inter- and intra-individual variability is generally low.
In vitro, metabolites result from non-enzymatic degradation and there is no evidence of cytochrome P450-mediated biotransformation of the diaminocyclohexane (DACH) ring.
Oxaliplatin is highly metabolized in humans; no parent drug was detectable in plasma ultrafiltrate following a 2-hour infusion. Several cytotoxic metabolites including the monochloro-, dichloro- and diaquo-DACH platinum species have been identified in the systemic circulation, as have a number of inactive metabolites at later timepoints. Platinum is predominantly excreted in the urine, with clearance mainly occurring in the 48 hours following
administration.
At Day 5, approximately 54% of the dose is recovered in the urine and less than 3% in the feces.
A significant decrease in clearance from 17.6 ± 2.18 l/h to 9.95 ± 1.91 l/h has been observed in patients with
renal insufficiency together with a statistically significant decrease in distribution volume from 330 ± 40.9 to
241 ± 36.1 l. The effect of severe renal insufficiency on platinum clearance has not been studied.

The target organs identified in the species used in preclinical studies (mice, rats, dogs and/or monkeys) in
single-dose and repeated dose-studies included bone marrow, the gastrointestinal system, the kidney, the
testes, the nervous system and the heart. The toxicities in the target organs observed in animals are similar
to those observed with other platinum-based agents and other cytotoxic drugs, which interact with DNA,
used in the treatment of cancer in humans, with the exception of those on the heart. Effects on the heart
were only observed in the dog and included electrophysiological abnormalities with lethal ventricular
fibrillation. Cardiotoxicity is considered to be specific to dogs, not only because it was only observed in this
species, but also because doses similar to lethal doses in the dog (150 mg/m²) were well tolerated in
humans. Preclinical studies using rat sensory neurons suggested that the oxaliplatin-induced acute
neurosensory symptoms may be related to an interaction with voltage-gated Na+ channels.
Oxaliplatin is mutagenic and clastogenic in mammalian cells and has demonstrated embryo-fetal toxicity in
rats. Although no studies have been performed concerning its carcinogenic potential, oxaliplatin is
considered to be probably carcinogenic.

Lactose monohydrate.

The diluted drug must not be mixed with other medicines in the same infusion bag or infusion line. Oxaliplatin
may be co-administered with folinic acid, using a Y-line, according to the instructions for use presented in
section 6.6.
• DO NOT mix with alkaline medications or solutions, particularly 5-fluorouracil, folinic acid products
containing trometamol as an excipient, and trometamol salts of other medicines. Alkaline solutions and
medications negatively affect the stability of oxaliplatin (see section 6.6).
• DO NOT reconstitute or dilute with saline solutions or other solutions containing chloride ions (including
calcium, potassium and sodium chloride).
• DO NOT mix with other medicines in the same infusion bag or infusion line (see section 6.6 for
instructions on simultaneous administration of folinic acid).
• DO NOT use injection material containing aluminum.

3 years. Reconstituted solution in original vial: For microbiological and chemical reasons, the reconstituted solution must be diluted immediately. Solution for infusion: Physical and chemical stability after dilution of the reconstituted solution in 5% glucose solution (50 mg/ml) have been demonstrated for 24 hours between +2°C and +8°C. Nevertheless, for microbiological reasons, the solution for infusion must be used immediately. If the drug is not used immediately, the duration and conditions of storage before use are the sole responsibility of the user and should not exceed 24 hours at a temperature between +2°C and +8°C, unless dilution was performed in duly controlled and validated aseptic conditions.

This medicinal product does not require any special precautions for storage.

Reconstituted solution:
To be diluted immediately (see Section 6.3).
Solution for infusion:
To be stored between +2°C and +8°C for a maximum of 24 hours.
Inspect visually before use. Only clear solutions with no particles should be used.
The medicinal product is for single use only. Any unused solution must be discarded.

Powder (containing 20 mg of oxaliplatin) in 24 ml (type I colorless glass) vials with a chlorobutyl stopper; box
of 1.
Powder (containing 50 mg of oxaliplatin) in 36 ml (type I colorless glass) vials with a chlorobutyl stopper; box
of 1.
Powder (containing 100 mg of oxaliplatin) in 50 ml (type I colorless glass) vials with a chlorobutyl stopper;
box of 1.

As for any potentially toxic agent, caution should be exercised when handling and preparing oxaliplatin.
Instructions for handling
Handling of this cytotoxic agent by healthcare personnel requires a set of precautions to ensure the
protection of the handler and his/her surroundings.

The preparation of injectable solutions of cytotoxic agents must always be carried out by trained specialist
personnel with knowledge of the medicines used, in conditions ensuring drug integrity, the protection of the
environment and in particular protection of the personnel handling the medicines, according to hospital
practice. 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, particularly long-sleeved coats, protection
masks, caps, protective goggles, sterile disposable 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 and avoid handling cytotoxic agents.
Any broken container must be treated with the same precautions and considered as contaminated waste.
Contaminated waste must be incinerated in suitably labeled rigid containers (see section on waste disposal
below).
If the powder, the reconstituted solution or solution for infusion should come into contact with the skin,
immediately remove carefully with water.
If the powder, the reconstituted solution or solution for infusion should come into contact with mucous
membranes, immediately remove carefully with water.
These provisions can be considered as part of the oncology network (Circular DGS/DH/98 No. 98/18 dated
March 24, 1998), in collaboration with any appropriate unit that fulfils the conditions required.
Special precautions for administration
• NEVER use injection material containing aluminum.
• NEVER administer undiluted.
• Only use a 5% glucose solution (50 mg/ml) to dilute. DO NOT use solutions containing chloride or
sodium chloride to reconstitute or dilute for infusion.
• NEVER mix with any other medicines in the same infusion bag, or administer simultaneously by the
same infusion line. DO NOT mix with alkaline medications or solutions, particularly 5-fluorouracil, folinic
acid products containing trometamol as an excipients, and trometamol salts of other active substances.
Alkaline solutions and medications negatively affect the stability of oxaliplatin.
Instructions for use with folinic acid (such as disodium folinate or calcium folinate)
An IV infusion of oxaliplatin 85 mg/m2 in 250 to 500 ml of 5% glucose solution (50 mg/ml) is administered at
the same time as an IV infusion of folinic acid in a 5% glucose solution (50 mg/ml), for 2 to 6 hours, using a
Y-line placed just ahead of the injection site. 

These two medicines must not be mixed in the same infusion bag. Folinic acid must not contain trometamol as an excipient and must only be diluted in 5% isotonic glucose solution (50 mg/ml), never in alkaline solutions or solutions containing chloride or sodium chloride.
Instructions for use with 5-fluorouracil
Oxaliplatin must always be administered before fluoropyrimidines, i.e. 5-fluorouracil.
After oxaliplatin administration, rinse the infusion line and then administer 5-fluorouracil.
For more information on medicines combined with oxaliplatin, see the respective manufacturer’s SPC.
Use only the recommended solvents (see below).
Any reconstituted solution showing traces of precipitation must not be administered and must be disposed of in compliance with the regulatory requirements concerning the elimination of toxic waste (see below).
Solution reconstitution
• Water for injections or a 5% glucose solution (50 mg/ml) should be used to reconstitute the solution.
• For a 20 mg vial: add 4 ml of the solvent to obtain an oxaliplatin concentration of 5 mg/ml.
• For a 50 mg vial: add 10 ml of the solvent to obtain an oxaliplatin concentration of 5 mg/ml.
• For a 100 mg vial: add 20 ml of the solvent to obtain an oxaliplatin concentration of 5 mg/ml.
For microbiological and chemical reasons, the reconstituted solution should be diluted immediately with a 5% glucose solution (50 mg/ml).
Inspect visually before use. Only clear solutions with no particles can be used.
The medicinal product is for single use only. Any unused solution must be disposed of.
Dilution for intravenous infusion
Withdraw the required amount of reconstituted solution from the vial and then dilute with 250 to 500 ml of 5% glucose solution (50 mg/ml) to obtain an oxaliplatin concentration of between 0.2 mg/ml and 0.7 mg/ml. The concentration range for which the physical and chemical stability of oxaliplatin have been demonstrated is between 0.2 mg/ml and 2.0 mg/ml.
Administer by intravenous infusion.
Physical and chemical stability after dilution in 5% glucose solution (50 mg/ml) have been demonstrated for 24 hours between +2°C and +8°C.
For microbiological reasons, the solution for infusion must be used immediately.
If the drug is not used immediately, the duration and conditions of storage before use are the sole responsibility of the user and should usually not exceed 24 hours at a temperature between +2°C and +8°C, unless dilution was performed in controlled and validated aseptic conditions.
Inspect visually before use. Only clear solutions with no particles can be used.
The medicinal product is for single use only. Any unused solution must be disposed of (see section on waste disposal below).
NEVER use solutions containing chloride or sodium chloride for reconstitution or dilution.
The compatibility of the oxaliplatin solution for infusion has been tested with standard PVC-based administration sets.
Infusion
The administration of oxaliplatin does not require prehydration.
Oxaliplatin diluted in 250 to 500 ml 5% glucose solution (50 mg/ml) to obtain a concentration greater than 0.2 mg/ml must be infused either in peripheral a vein or using central venous line over 2 to 6 hours. When oxaliplatin is administered with 5-fluorouracil, the oxaliplatin infusion must be given before 5-fluorouracil.
Waste disposal

Any unused product, as well as all materials that have been used for reconstitution, dilution and administration, must be destroyed according to standard hospital procedures relative to cytotoxic agents as per current laws related to the disposal of toxic waste.