Oxaliplatin

What it is and how it works

Mechanism of Action 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.

Indications

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 injection 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.

Dosage and administration (summary)

• 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. 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.

Contraindications

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. ( 4 , 5.1 )

Warnings and precautions

• 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 x 10 9 /L and platelets are greater than or equal to 75 x 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.

Pregnancy

Pregnancy Risk Summary Based on its direct interaction with DNA, oxaliplatin can cause fetal harm when administered to a pregnant woman. The available human data do not establish the presence or absence of major birth defects or miscarriage related to the use of oxaliplatin.

Storage and supply

Oxaliplatin injection, USP is supplied in clear, glass, single-dose vials with grey rubber stoppers and aluminum flip-off seals containing 50 mg/10 mL or 100 mg/20 mL of oxaliplatin as a sterile, clear, colorless, preservative-free, aqueous solution at a concentration of 5 mg/mL.

Source: Oxaliplatin (Oxaliplatin) — US FDA prescribing information, 2023-07-20, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.