Oxaliplatin

OXALIPLATIN- oxaliplatin injection, solution, concentrate
Hospira, Inc.

1 INDICATIONS AND USAGE

Oxaliplatin, in combination with infusional fluorouracil and leucovorin, is indicated for:

• adjuvant treatment of stage III colon cancer in patients who have undergone complete resection of the primary tumor.
• treatment of advanced colorectal cancer.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

Administer Oxaliplatin in combination with fluorouracil and leucovorin every 2 weeks.

• For adjuvant treatment, continue treatment for up to 12 cycles or unacceptable toxicity.
• For advanced colorectal cancer, continue treatment until disease progression or unacceptable toxicity.

Day 1

Administer Oxaliplatin 85 mg/m² as an intravenous infusion over 120 minutes and leucovorin 200 mg/m² as an intravenous infusion over 120 minutes at the same time in separate bags, followed by fluorouracil 400 mg/m² as intravenous bolus over 2 to 4 minutes, followed by fluorouracil 600 mg/m² as a 22-hour continuous infusion.

Day 2

Administer leucovorin 200 mg/m² as an intravenous infusion over 120 minutes, followed by fluorouracil 400 mg/m² as intravenous bolus over 2 to 4 minutes, followed by fluorouracil 600 mg/m² as a 22-hour continuous infusion.

Refer to the prescribing information for fluorouracil and leucovorin for additional information.

2.2 Dose Modifications for Adverse Reactions

Prolongation of infusion time for Oxaliplatin from 2 hours to 6 hours may mitigate acute toxicities, such as non-life threatening infusion-related reactions.

Permanently discontinue Oxaliplatin for any of the following:

• Hypersensitivity Reactions [see Warnings and Precautions (5.1)]
• Posterior reversible encephalopathy syndrome (PRES) [see Warnings and Precautions (5.4)]
• Confirmed interstitial lung disease or pulmonary fibrosis [see Warnings and Precautions (5.5)]
• Rhabdomyolysis [see Warnings and Precautions (5.8)]

Refer to the fluorouracil and leucovorin prescribing information for dosage modifications for adverse reactions.

Dosage Modifications for Adjuvant Treatment

Dosage modifications for adverse reactions for adjuvant treatment are presented in Table 1.

Table 1: Dosage Modifications for Adjuvant Treatment in Patients with Stage III Colon Cancer

Adverse Reactions	Severity	Oxaliplatin Dosage Modifications
Peripheral Sensory Neuropathy [see Warnings and Precautions (5.2)]	Persistent Grade 2	Consider reducing Oxaliplatin dose to 75 mg/m2.
	Persistent Grade 3	Consider discontinuing Oxaliplatin.
	Grade 4	Discontinue Oxaliplatin.
Myelosuppression [see Warnings and Precautions (5.3), Adverse Reactions (6.1)]	Grade 4 neutropenia or febrile neutropenia	Delay the next dose until neutrophils greater than or equal to 1.5 × 109 /L and platelets greater than or equal to 75 × 109 /L.Reduce Oxaliplatin dose to 75 mg/m2.
	Grade 3–4 thrombocytopenia
Gastrointestinal Adverse Reactions [see Adverse Reactions (6.1)]	Grade 3–4	After recovery, reduce Oxaliplatin dose to 75 mg/m2 along with a dose reduction of fluorouracil to 300 mg/m2 as an intravenous bolus and 500 mg/m2 as a 22-hour continuous infusion.

Dosage Modifications for Advanced Colorectal Cancer

Dosage modifications for adverse reactions for advanced colorectal cancer are presented in Table 2.

Table 2: Dosage Modifications for Advanced Colorectal Cancer

Adverse Reactions	Severity	Oxaliplatin Dosage Modifications
Neuropathy [see Warnings and Precautions (5.2)]	Persistent Grade 2	Consider reducing Oxaliplatin dose to 65 mg/m2.
	Persistent Grade 3	Consider discontinuing Oxaliplatin.
	Grade 4	Discontinue Oxaliplatin.
Myelosuppression [see Warnings and Precautions (5.3), Adverse Reactions (6.1)]	Grade 4 neutropenia or febrile neutropenia	Delay the next dose until neutrophils greater than or equal to 1.5 × 109 /L and platelets greater than or equal to 75 × 109 /L.Reduce Oxaliplatin dose to 65 mg/m2.
	Grade 3–4 thrombocytopenia
Gastrointestinal Adverse Reactions [see Adverse Reactions 6.1)]	Grade 3–4	After recovery, reduce Oxaliplatin dose to 65 mg/m2 along with a dose reduction of fluorouracil to 300 mg/m2 as an intravenous bolus and 500 mg/m2 as a 22-hour continuous infusion.

2.3 Dose Modifications for Patients with Renal Impairment

In patients with severe renal impairment (creatinine clearance [CLcr] less than 30 mL/min, calculated by the Cockcroft-Gault equation), reduce the Oxaliplatin dose to 65 mg/m² [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

2.4 Preparation and Administration

• Oxaliplatin is a cytotoxic drug. Follow applicable special handling and disposal procedures.¹
• Do not freeze.
• Protect the concentrated solution from light.
• Dilute concentrated solution with 250 to 500 mL of 5% Dextrose Injection, USP. Do not dilute with sodium chloride solution or other chloride-containing solutions.
• Store diluted solution for no more than 6 hours at room temperature (20°C to 25°C [68°F to 77°F]) or 24 hours under refrigeration (2°C to 8°C [36°F to 46°F]). Protection from light is not required.
• Visually inspect for particulate matter and discoloration prior to administration and discard if present.
• Do not mix Oxaliplatin or administer Oxaliplatin through the same infusion line concurrently with alkaline medications or media (such as basic solutions of fluorouracil).
• Flush the infusion line with 5% Dextrose Injection, USP prior to administration of any concomitant medication.
• Do not use needles or intravenous administration sets containing aluminum parts for the preparation or mixing of Oxaliplatin. Aluminum has been reported to cause degradation of platinum compounds.
• Administer Oxaliplatin as an intravenous infusion over 120 minutes concurrently with leucovorin over 120 minutes in separate bags.