OXALIPLATIN HOSPIRA 5MG/ML, 100MG/20ML [SIN13943P]

Product Info

OXALIPLATIN HOSPIRA 5MG/ML, 100MG/20ML

[SIN13943P]

4.1 Therapeutic Indications

Oxaliplatin, in combination with fluorouracil and folinic acid, is indicated for:

• adjuvant treatment of stage III (Duke’s C) colon cancer after complete resection of the primary tumour

• treatment of metastatic colorectal cancer

4.2 Dose and Method of Administration

Dosage

In combination with fluorouracil and folinic acid the recommended dose for the treatment of metastatic colorectal cancer is 85 mg/m² intravenously repeated every two weeks.

In combination with fluorouracil and folinic acid the recommended dose for adjuvant treatment is 85 mg/m² intravenously repeated every two weeks for 12 cycles (6 months).

Dosage Modification

Prior to each treatment cycle, patients should be evaluated for toxicity and the dose of oxaliplatin adjusted accordingly.

Neurological Toxicity

If acute neurological reactions occur, e.g., acute pharyngolaryngeal dysaesthesia, increase the oxaliplatin infusion time from 2 hours to 6 hours. This decreases C_max by 30% and may lessen acute toxicities.

If symptoms last longer than seven 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 paraesthesia 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 paraesthesia 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.

Haematological Toxicity

If haematological toxicity (neutrophils <1.5 x 10⁹/L or platelets <75 x 10⁹/L) is present before starting treatment or prior to the next course:

• Delay treatment until neutrophil count is ≥1.5 x 10⁹/L and platelet count is ≥75 x 10⁹/L and

• Reduce the 85 mg/m² oxaliplatin dose to 75 mg/m² every two weeks in addition to any fluorouracil (FU) dose adjustment (adjuvant setting)

• Reduce the 85 mg/m² oxaliplatin dose to 65 mg/m² every two weeks in addition to any FU dose adjustment (metastatic setting).

Gastrointestinal Toxicity

If Grade 3–4 gastrointestinal reactions occur, as assessed according to US National Cancer Institute criteria:

• Delay treatment until resolution of the adverse reactions and

• Reduce the 85 mg/m² oxaliplatin dose to 75 mg/m² every two weeks in addition to any FU dose adjustment (adjuvant setting)

• Reduce the 85 mg/m² oxaliplatin dose to 65 mg/m² every two weeks in addition to any FU dose adjustment (metastatic setting)

Toxicity Associated with Fluorouracil

Dose adjustments should also be made for fluorouracil associated toxicities (see relevant Product Information).

Oxaliplatin should be administered before fluorouracil.

Oxaliplatin is administered as a 2- to 6-hour intravenous infusion in 250 to 500 mL of 5% glucose injection.

Method of Administration

Special Precautions for Administration

• DO NOT use any injection material containing aluminium.

• DO NOT administer undiluted.

• DO NOT mix or administer with sodium chloride injection or any other solution containing chlorides.

• DO NOT mix with any other medication or administer simultaneously by the same infusion line (in particular fluorouracil and folinic acid). A Y-tube may be used (see Administration).

• USE ONLY the recommended diluents (see below).

Handling

As with other potentially toxic compounds, caution should be exercised when handling and preparing oxaliplatin solutions.

The handling of this cytotoxic agent by health care personnel requires every precaution to guarantee the protection of the handler and their surroundings. It is essential to use appropriate protective clothing, including protective goggles, mask and gloves. Pregnant women must be warned to avoid handling cytotoxic agents. If premixed solution or infusion solution should come into contact with skin, mucous membranes or eyes, wash immediately and thoroughly with water.

Preparation

Dilution of Concentrate before Infusion

The solution must be further diluted in an infusion solution of 250–500 mL of 5% glucose injection. From a microbiological and chemical point of view, this infusion preparation should be used immediately. Inspect visually prior to use. Only clear solutions without particles should be used. The product contains no preservative and is for single use only. Discard any remaining contents. NEVER use sodium chloride solution for dilution.

Administration

The administration of oxaliplatin does not require prehydration. Oxaliplatin diluted in 250 to 500 mL of a glucose 5% injection must be infused either by central venous line or peripheral vein over 2 to 6 hours. When oxaliplatin is administered with fluorouracil, the oxaliplatin infusion should precede that of fluorouracil.

Oxaliplatin can be co-administered with folinic acid infusion using a Y-tube placed immediately before the site of injection. The medicines should not be combined in the same infusion bag. Folinic acid must be diluted using isotonic infusion solutions such as 5% glucose solution but NOT sodium chloride solutions or alkaline solutions.

Flush the line after oxaliplatin administration.

While oxaliplatin has minimal to no vesicant potential, extravasation may result in local pain and inflammation which may be severe and lead to complications especially when oxaliplatin is infused through a peripheral vein. In case of oxaliplatin extravasation, the infusion must be stopped immediately and the usual local symptomatic treatment initiated.

To reduce microbiological hazard, use as soon as practicable after preparation. If storage is necessary, hold at 2° – 8°C for not more than 24 hours.

4.3 Contraindications

Oxaliplatin is contraindicated in patients who:

• have a known history of hypersensitivity to oxaliplatin, any of the excipients or other platinum compounds

• are pregnant

• are breastfeeding

• have myelosuppression prior to starting first course, as evidenced by baseline neutrophils <1.5 x 10⁹/L and/or platelet count of <75 x 10⁹/L

• have a peripheral sensory neuropathy with functional impairment prior to first course

• have severely impaired renal function (creatinine clearance less than 30 mL/min)

• if contraindications exist to any of the agents in combination regimens, that agent should not be used.