Oxaliplatin

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 injection dose to 65 mg/m 2 [see Use in Specific Populations , Clinical Pharmacology ] .

Dose Modifications for Adverse Reactions Prolongation of infusion time for oxaliplatin injection from 2 hours to 6 hours may mitigate acute toxicities, such as non-life-threatening infusion-related reactions. Permanently discontinue oxaliplatin injection for any of the following:

Hypersensitivity Reactions [see Warnings and Precautions ]

Posterior reversible encephalopathy syndrome (PRES) [see Warnings and Precautions ]

Confirmed interstitial lung disease or pulmonary fibrosis [see Warnings and Precautions ]

Rhabdomyolysis [see Warnings and Precautions ] 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 Injection Dosage Modifications Peripheral Sensory Neuropathy [see Warnings and Precautions ] Persistent Grade 2 Consider reducing oxaliplatin injection dose to 75 mg/m 2 .

Persistent Grade 3 Consider discontinuing oxaliplatin injection. Grade 4 Discontinue oxaliplatin injection. Myelosuppression [see Warnings and Precautions , Adverse Reactions ]. Grade 4 neutropenia or febrile neutropenia Delay the next dose until neutrophils greater than or equal to 1.5 × 10 9 /L and platelets greater than or equal to 75 × 10 9 /L.

Reduce oxaliplatin injection dose to 75 mg/m 2 . Grade 3 to 4 thrombocytopenia Gastrointestinal Adverse Reactions [see Adverse Reactions ] Grade 3 to 4 After recovery, reduce oxaliplatin injection dose to 75 mg/m 2 along with a dose reduction of fluorouracil to 300 mg/m 2 as an intravenous bolus and 500 mg/m 2 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 Injection Dosage Modifications Neuropathy [see Warnings and Precautions ] Persistent Grade 2 Consider reducing oxaliplatin injection dose to 65 mg/m 2 .

Persistent Grade 3 Consider discontinuing oxaliplatin injection. Grade 4 Discontinue oxaliplatin injection. Myelosuppression [see Warnings and Precautions , Adverse Reactions ] Grade 4 neutropenia or febrile neutropenia Delay the next dose until neutrophils greater than or equal to 1.5 × 10 9 /L and platelets greater than or equal to 75 × 10 9 /L.

Reduce oxaliplatin injection dose to 65 mg/m 2 . Grade 3 to 4 thrombocytopenia Gastrointestinal Adverse Reactions [see Adverse Reactions ] Grade 3 to 4 After recovery, reduce oxaliplatin injection dose to 65 mg/m 2 along with a dose reduction of fluorouracil to 300 mg/m 2 as an intravenous bolus and 500 mg/m 2 as a 22-hour continuous infusion.

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 injection or administer oxaliplatin injection 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 injection. Aluminum has been reported to cause degradation of platinum compounds. Administer oxaliplatin injection as an intravenous infusion over 120 minutes concurrently with leucovorin over 120 minutes in separate bags.