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. Oxaliplatin is a platinum-based drug used in combination with infusional fluorouracil and leucovorin, which 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.

Oxaliplatin undergoes nonenzymatic conversion in physiologic solutions to active derivatives via displacement of the labile oxalate ligand. Several transient reactive species are formed, including monoaquo and diaquo DACH platinum, which covalently bind with macromolecules. Both inter- and intrastrand Pt-DNA crosslinks are formed. Crosslinks are formed between the N7 positions of two adjacent guanines (GG), adjacent adenine-guanines (AG), and guanines separated by an intervening nucleotide (GNG). These crosslinks inhibit DNA replication and transcription. Cytotoxicity is cell-cycle nonspecific. In vivo studies have shown antitumor activity of oxaliplatin against colon carcinoma.

Administer oxaliplatin injection 85 mg/m 2 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. Adjuvant Treatment: Continue treatment for up to 12 cycles or unacceptable toxicity. Advanced Colorectal Cancer: Continue treatment until disease progression or unacceptable toxicity.

Oxaliplatin is contraindicated in patients with a history of a hypersensitivity reaction to oxaliplatin or other platinum-based drugs. Reactions have included anaphylaxis. History of hypersensitivity reaction to oxaliplatin or other platinum-based drugs.

Boxed warning (hypersensitivity reactions, including anaphylaxis): Serious and fatal hypersensitivity adverse reactions, including anaphylaxis, can occur with oxaliplatin within minutes of administration and during any cycle. Oxaliplatin is contraindicated in patients with hypersensitivity reactions to oxaliplatin and other platinum-based drugs. Peripheral Sensory Neuropathy: Acute and delayed neuropathy can occur. Avoid topical application of ice. Reduce the dose or permanently discontinue oxaliplatin as recommended. Severe Myelosuppression: Delay oxaliplatin until neutrophils are greater than or equal to 1.5 × 10 9 /L and platelets are greater than or equal to 75 × 10 9 /L. Withhold oxaliplatin for sepsis or septic shock. Dose reduce after recovery from grade 4 neutropenia, febrile neutropenia, or grade 3 to 4 thrombocytopenia as recommended.

The following clinically significant adverse reactions are described elsewhere in labeling: Hypersensitivity Reactions Peripheral Sensory Neuropathy Severe Myelosuppression Reversible Posterior Leukoencephalopathy Syndrome Pulmonary Toxicity Hepatotoxicity QT Interval Prolongation and Ventricular Arrhythmias Rhabdomyolysis Hemorrhage Most common adverse reactions (incidence greater than or equal to 40%) were peripheral sensory neuropathy, neutropenia, thrombocytopenia, anemia, nausea, increase in transaminases and alkaline phosphatase, diarrhea, emesis, fatigue, and stomatitis.

Drugs that Prolong the QT Interval QT interval prolongation and ventricular arrhythmias can occur with oxaliplatin. Avoid coadministration of oxaliplatin with medicinal products with a known potential to prolong the QT interval.

Store at 20° to 25°C (68° to 77°F), excursions permitted to 15° to 30°C (59° to 86°F). Do not freeze and protect from light (keep in original outer carton).