Oxaliplatin

Oxaliplatin injection, 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.

• •Administer oxaliplatin injection 85 mg/m² as an intravenous infusion over 120 minutes concurrently with leucovorin over 120 minutes in separate bags, followed by fluorouracil on Day 1 of each 14-day cycle. Administer fluorouracil and leucovorin on Day 2 as recommended. (
  2.1 Recommended Dosage

  Administer oxaliplatin injection 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 injection 85 mg/m²as an intravenous infusion over 120 minutes and leucovorin 200 mg/m²as an intravenous infusion over 120 minutes at the same time in separate bags, followed by fluorouracil 400 mg/m²as intravenous bolus over 2 to 4 minutes, followed by fluorouracil 600 mg/m²as a 22-hour continuous infusion.

  Day 2

  Administer leucovorin 200 mg/m²as an intravenous infusion over 120 minutes, followed by fluorouracil 400 mg/m²as intravenous bolus over 2 to 4 minutes, followed by fluorouracil 600 mg/m²as a 22-hour continuous infusion.

  Refer to the prescribing information for fluorouracil and leucovorin for additional information.
  )
• •
  Adjuvant Treatment
  : Continue treatment for up to 12 cycles or unacceptable toxicity. (
  2.1 Recommended Dosage

  Administer oxaliplatin injection 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 injection 85 mg/m²as an intravenous infusion over 120 minutes and leucovorin 200 mg/m²as an intravenous infusion over 120 minutes at the same time in separate bags, followed by fluorouracil 400 mg/m²as intravenous bolus over 2 to 4 minutes, followed by fluorouracil 600 mg/m²as a 22-hour continuous infusion.

  Day 2

  Administer leucovorin 200 mg/m²as an intravenous infusion over 120 minutes, followed by fluorouracil 400 mg/m²as intravenous bolus over 2 to 4 minutes, followed by fluorouracil 600 mg/m²as a 22-hour continuous infusion.

  Refer to the prescribing information for fluorouracil and leucovorin for additional information.
  )
• •
  Advanced Colorectal Cancer
  : Continue treatment until disease progression or unacceptable toxicity. (
  2.1 Recommended Dosage

  Administer oxaliplatin injection 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 injection 85 mg/m²as an intravenous infusion over 120 minutes and leucovorin 200 mg/m²as an intravenous infusion over 120 minutes at the same time in separate bags, followed by fluorouracil 400 mg/m²as intravenous bolus over 2 to 4 minutes, followed by fluorouracil 600 mg/m²as a 22-hour continuous infusion.

  Day 2

  Administer leucovorin 200 mg/m²as an intravenous infusion over 120 minutes, followed by fluorouracil 400 mg/m²as intravenous bolus over 2 to 4 minutes, followed by fluorouracil 600 mg/m²as a 22-hour continuous infusion.

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

Injection: 50 mg (5 mg/mL) or 100 mg (5 mg/mL) clear, colorless solution in a single-dose vial.

• •
  Females
  : Advise female patients of reproductive potential to use effective contraception while receiving oxaliplatin and for 9 months after the final dose. (
  8.3 Females and Males of Reproductive Potential

  Pregnancy Testing

  Verify pregnancy status in females of reproductive potential prior to initiating oxaliplatin

  [see Use in Specific Populations ]

  .

  Contraception

  Oxaliplatin can cause embryo-fetal harm when administered to a pregnant woman

  [see Use in Specific Populations (

  8.1)]

  .

  Females

  Advise female patients of reproductive potential to use effective contraception while receiving oxaliplatin and for 9 months after the final dose.

  Males

  Based on its mechanism action as a genotoxic drug, advise males with female partners of reproductive potential to use effective contraception while receiving oxaliplatin and for 6 months after the final dose

  [see Nonclinical Toxicology (

  13.1)]

  .

  Infertility

  Based on animal studies, oxaliplatin may impair fertility in males and females

  [see Nonclinical Toxicology (

  13.1)]

  .
  )
• •
  Males
  : Based on its mechanism action as a genotoxic drug, advise males with female partners of reproductive potential to use effective contraception while receiving oxaliplatin and for 6 months after the final dose
  [see Nonclinical Toxicology (

  13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

  Long-term animal studies have not been performed to evaluate the carcinogenic potential of oxaliplatin. Oxaliplatin was not mutagenic to bacteria (Ames test) but was mutagenic to mammalian cells

  in vitro

  (L5178Y mouse lymphoma assay). Oxaliplatin was clastogenic both

  in vitro

  (chromosome aberration in human lymphocytes) and

  in vivo

  (mouse bone marrow micronucleus assay).

  In a fertility study, male rats were given oxaliplatin at 0, 0.5, 1, or 2 mg/kg/day for five days every 21 days for a total of three cycles prior to mating with females that received two cycles of oxaliplatin on the same schedule. A dose of 2 mg/kg/day (less than one-seventh the recommended human dose on a body surface area basis) did not affect pregnancy rate, but resulted in 97% postimplantation loss (increased early resorptions, decreased live fetuses, decreased live births), and delayed growth (decreased fetal weight).

  Testicular damage, characterized by degeneration, hypoplasia, and atrophy, was observed in dogs administered oxaliplatin at 0.75 mg/kg/day (approximately one-sixth of the recommended human dose on a body surface area basis) × 5 days every 28 days for three cycles. A no effect level was not identified.

  )].