Vexplatin-50/Vexplatin-100 Special Precautions

General: Oxaliplatin should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents.
Neuropathy - Previously Unrated and Previously Treated Patients with Advanced Colorectal Cancer: In the previously treated study, neuropathy information was collected to establish that Oxaliplatin in associated with two types of neuropathy.
Pulmonary Toxicity: Oxaliplatin has been associated with pulmonary fibrosis (< 1% of study patients), which may be fatal.
Hepatotoxicity: Hepatotoxicity as evidenced in the adjuvant study, by increase in transaminases (57% vs. 34%) and alkaline phosphatase (42% vs. 20%) was observed more commonly in the Oxaliplatin combination arm than in the control arm.
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 caused developmental mortality (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 x 5 days every 28 days for three cycles.
Patients with Renal impairment: The exposure (AUC) of unbound platinum in plasma ultrafiltrate tends to increase in renally impaired patients. Caution and close monitoring should be exercised when Oxaliplatin is administered to patients with renal impairment. The starting Oxaliplatin dose does not need to be reduced in patients with mild (creatinine clearance=50-80 mL/min) or moderate (creatinine clearance=30-49 mL/min) renal impairment. However, the starting dose of Oxaliplatin should be reduced in patients with severe renal impairment (creatinine clearance< 30 mL/min).
Use in Pregnancy: Pregnancy Category D: Oxaliplatin may cause fetal harm when administered to a pregnant woman.
Use in Lactation: It is not known whether Oxaliplatin or its derivatives are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Oxaliplatin, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Use in Children: The effectiveness of oxaliplatin in children has not been established.
Use in the Elderly: No significant effect of age on the clearance of ultrafilterable platinum has been observed. No adjustment to starting dose was required in patient's ≥65 years old.