It is a platinum-based drug used in combination with infusional 5? fluorouracil /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. In combination with 5-fluorouracil, oxaliplatin exhibits in vitro and in vivo antiproliferative activity greater than either compound alone in several tumor models [HT29 (colon), GR (mammary), and L1210 (leukemia)].
Administer It in combination with 5-fluorouracil/leucovorin every 2 weeks.: ? Day 1: It 85 mg/m2 intravenous infusion in 250-500 mL 5% Dextrose Injection,USPand leucovorin 200 mg/m2 intravenous infusion in 5% Dextrose Injection,USP both given over 120 minutes at the same time in separate bags using a Y-line,followed by 5-fluorouracil 400 mg/m2 intravenous bolus given over 2-4 minutes,followed by 5? fluorouracil 600 mg/m2 intravenous infusion in 500 mL 5% Dextrose Injection,USP (recommended) as a 22-hour continuous infusion. ? Day 2: leucovorin 200 mg/m2 intravenous infusion over 120 minutes, followed by 5-fluorouracil 400 mg/m2 IV bolus given over 2-4 minutes, followed by 5-fluorouracil 600 mg/m2 intravenous infusion in 500 mL 5% Dextrose Injection,USP (recommended) as a 22-hour continuous infusion. ? Reduce the dose of It to 75 mg/m? (adjuvant setting) or 65 mg/m? (advanced colorectal cancer: ? if there are persistent grade 2 neurosensory events that do not resolve. ? after recovery from grade 3/4 gastrointestinal toxicities (despite prophylactic treatment) or grade 4 neutropenia or grade 3/4 thrombocytopenia. Delay next dose until neutrophils ?1.5 x 109 /L and platelets ?75 x 109 /L. ? For patients with severe renal impairment (creatinine clearance <30 mL/min),the initial recommended dose is 65 mg/m?. ? Discontinue It if there are persistent Grade 3 neurosensory events. ? Never reconstitute or prepare final dilution with a sodium chloride solution or other chloride-containing solutions.
No specific cytochrome P-450-based drug interaction studies have been conducted. No pharmacokinetic interaction between 85 mg/m² oxaliplatin and 5-fluorouracil/folinic acid has been observed in patients treated every 2 weeks. Increases of 5-fluorouracil plasma concentrations by approximately 20% have been observed with doses of 130 mg/m² oxaliplatin dosed every 3 weeks. Because platinum-containing species are eliminated primarily through the kidney, clearance of these products may be decreased by coadministration of potentially nephrotoxic compounds; although, this has not been specifically studied.
Known allergy to It or other platinum compounds.
Peripheral sensory neuropathy,neutropenia,thrombocytopenia,anemia,nausea,increase in transaminases and alkaline phosphatase,diarrhea,emesis,fatigue and stomatitis.
Category D: There is positive evidence of human foetal risk,but the benefits from use in pregnant women may be acceptable despite the risk (e.g.,if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
There is no known antidote for oxaliplatin overdose. In addition to thrombocytopenia, the anticipated complications of an oxaliplatin overdose include hypersensitivity reaction, myelosuppression, nausea, vomiting, diarrhea and neurotoxicity. Several cases of overdoses have been reported with oxaliplatin. Adverse reactions observed were Grade 4 thrombocytopenia (<25,000/mm3) without any bleeding, anemia, sensory neuropathy such as paresthesia, dysesthesia, laryngospasm and facial muscle spasms, gastrointestinal disorders such as nausea, vomiting, stomatitis, flatulence, abdomen enlarged and Grade 4 intestinal obstruction, Grade 4 dehydration, dyspnea, wheezing, chest pain, respiratory failure, severe bradycardia and death. Patients suspected of receiving an overdose should be monitored, and supportive treatment should be administered. The maximum dose of oxaliplatin that has been administered in a single infusion is 825 mg.
Store in a cool & dry place, protected from light and moisture. Keep out of reach of children.
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