ELOXATIN, used in combination with infusional 5-FU/LV, is indicated for:

• adjuvant treatment of stage III colon cancer in patients who have undergone complete resection of the primary tumor. The indication is based on an improvement in disease-free survival, with no demonstrated benefit in overall survival after a median follow up of 4 years.
• treatment of advanced colorectal cancer.

ELOXATIN (oxaliplatin injection) should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate diagnostic and treatment facilities are readily available.

Dosage

Administer ELOXATIN in combination with 5-FU/LV every 2 weeks. For advanced disease, treatment is recommended until disease progression or unacceptable toxicity. For adjuvant use, treatment is recommended for a total of 6 months (12 cycles):

Day 1: ELOXATIN 85 mg/m² IV infusion in 250-500 mL 5% Dextrose injection, USP (D5W) and leucovorin 200 mg/m² IV infusion in D5W both given over 120 minutes at the same time in separate bags using a Y-line, followed by 5-FU 400 mg/m² IV bolus given over 2-4 minutes, followed by 5-FU 600 mg/m IV infusion in 500 mL D5W (recommended) as a 22-hour continuous infusion.

Day 2: Leucovorin 200 mg/m² IV infusion over 120 minutes, followed by 5-FU 400 mg/m² IV bolus given over 2-4 minutes, followed by 5-FU 600 mg/m²IV infusion in 500 mL D5W (recommended) as a 22-hour continuous infusion.

Figure 1

The administration of ELOXATIN does not require prehydration. Premedication with antiemetics, including 5-HT₃ blockers with or without dexamethasone, is recommended.

For information on 5-fluorouracil and leucovorin, see the respective package inserts.

Dose Modification Recommendations

Prior to subsequent therapy cycles, patients should be evaluated for clinical toxicities and recommended laboratory tests [see WARNINGS and PRECAUTIONS]. Prolongation of infusion time for ELOXATIN from2 hours to 6 hours may mitigate acute toxicities. The infusion times for 5-FU and leucovorin do not need to be changed.

Adjuvant Therapy in Patients with Stage III Colon Cancer

Neuropathy and other toxicities were graded using the NCI CTC scale version 1 [see WARNINGS and PRECAUTIONS].

For patients who experience persistent Grade 2 neurosensory events that do not resolve, a dose reduction of ELOXATIN to 75 mg/m² should be considered. For patients with persistent Grade 3 neurosensory events, discontinuing therapy should be considered. The infusional 5-FU/LV regimen need not be altered.

A dose reduction of ELOXATIN to 75 mg/m² and infusional 5-FU to 300 mg/m² bolus and 500 mg/m² 22 hour infusion is recommended for patients after recovery fromgrade 3/4 gastrointestinal (despite prophylactic treatment) or grade 4 neutropenia or grade 3/4 thrombocytopenia. The next dose should be delayed until: neutrophils ≥ 1.5 x 10⁹/L and platelets ≥ 75 x 10⁹/L.

Dose Modifications in Therapy in Previously Untreated and Previously Treated Patients with Advanced Colorectal Cancer

Neuropathy was graded using a study-specific neurotoxicity scale [see WARNINGS and PRECAUTIONS]. Other toxicities were graded by the NCI CTC, Version 2.0.

For patients who experience persistent Grade 2 neurosensory events that do not resolve, a dose reduction of ELOXATIN to 65 mg/m² should be considered. For patients with persistent Grade 3 neurosensory events, discontinuing therapy should be considered. The 5-FU/LV regimen need not be altered.

A dose reduction of ELOXATIN to 65 mg/m² and 5-FU by 20% (300 mg/m² bolus and 500 mg/m² 22-hour infusion) is recommended for patients after recovery fromgrade 3/4 gastrointestinal (despite prophylactic treatment) or grade 4 neutropenia or grade 3/4 thrombocytopenia. The next dose should be delayed until: neutrophils ≥ 1.5 x 10⁹/L and platelets ≥ 75 x 10⁹/L.

Preparation of Infusion Solution

Reconstitution or final dilution must never be performed with a sodiumchloride solution or other chloride containing solutions.

The lyophilized powder is reconstituted by adding 10 mL (for the 50 mg vial) or 20 mL (for the 100 mg vial) of Water for Injection, USP or 5% Dextrose Injection, USP. Do not administer the reconstituted solution without further dilution. The reconstituted solution must be further diluted in an infusion solution of 250-500 mL of 5% Dextrose Injection, USP.

After reconstitution in the original vial, the solution may be stored up to 24 hours under refrigeration [2-8°C (36-46°F)]. After final dilution with 250-500 mL of 5% Dextrose Injection, USP, the shelf life is 6 hours at roomtemperature [20-25°C (68-77°F)] or up to 24 hours under refrigeration [2-8°C (36-46°F)].

ELOXATIN is not light sensitive.

ELOXATIN is incompatible in solution with alkaline medications or media (such as basic solutions of 5-FU) and must not be mixed with these or administered simultaneously through the same infusion line. The infusion line should be flushed with D5W prior to administration of any concomitant medication.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration and discarded if present.

Needles or intravenous administration sets containing aluminumparts that may come in contact with ELOXATIN should not be used for the preparation or mixing of the drug. Aluminumhas been reported to cause degradation of platinumcompounds.

Dosage Forms and Strengths

ELOXATIN is supplied in single-use vials containing 50 mg or 100 mg of oxaliplatin as a sterile, preservative-free lyophilized powder for reconstitution.

ELOXATIN is supplied in clear, glass, single-use vials with gray elastomeric stoppers and aluminumflip-off seals containing 50 mg or 100 mg of oxaliplatin as a sterile, preservative-free lyophilized powder for reconstitution. Lactose monohydrate is also present as an inactive ingredient.

NDC 0024-0596-02: 50 mg single-use vial with green flip-off seal individually packaged in a carton.

NDC 0024-0597-04: 100 mg single-use vial with dark blue flip-off seal individually packaged in a carton.

Storage

Store under normal lighting conditions at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP controlled roomtemperature].

Handling and Disposal

As with other potentially toxic anticancer agents, care should be exercised in the handling and preparation of infusion solutions prepared fromELOXATIN. The use of gloves is recommended. If a solution of ELOXATIN contacts the skin, wash the skin immediately and thoroughly with soap and water. If ELOXATIN contacts the mucous membranes, flush thoroughly with water.

Procedures for the handling and disposal of anticancer drugs should be considered. Several guidelines on the subject have been published [see References]. There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

REFERENCES

1. NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings. 2004. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004-165.

2. OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling Occupational Exposure to Hazardous Drugs. OSHA, 1999. ttp://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html

3. NIH [2002]. 1999 recommendations for the safe handling of cytotoxic drugs. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, NIH Publication No. 92-2621.

4. American Society of Health-SystemPharmacists. (2006) ASHP Guidelines on Handling Hazardous Drugs.

5. Polovich, m., White, J. m., & Kelleher, L.O. (eds.) 2005. Chemotherapy and biotherapy guidelines and recommendations for practice (2nd. ed.) Pittsburgh, PA: Oncology Nursing Society.

Manufactured for: sanofi-aventis U.S. LLC Bridgewater, NJ 08807, ©2007 sanofi-aventis U.S. LLC. FDA revision date: 1/10/2007

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