Eloxatin - General Information
Eloxatin is a platinum-based chemotherapy drug in the same family as cisplatin and carboplatin. It is typically administered in combination with fluorouracil and leucovorin in a combination known as Folfox for the treatment of colorectal cancer. Compared to cisplatin the two amine groups are replaced by cyclohexyldiamine for improved antitumour activity. The chlorine ligands are replaced by the oxalato bidentate derived from oxalic acid in order to improve water solubility. Eloxatin is marketed by Sanofi-Aventis under the trademark Eloxatin®.
Pharmacology of Eloxatin
Eloxatin selectively inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of Eloxatin-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed.
Eloxatin for patients
Patients and patients caregivers should be informed of the expected side effects of ELOXATIN, particularly its neurologic effects, both the acute, reversible effects, and the persistent neurosensory toxicity. Patients should be informed that the acute neurosensory toxicity may be precipitated or exacerbated by exposure to cold or cold objects. Patients should be instructed to avoid cold drinks, use of ice, and should cover exposed skin prior to exposure to cold temperature or cold objects.
Patients must be adequately informed of the risk of low blood cell counts and instructed to contact their physician immediately should fever, particularly if associated with persistent diarrhea, or evidence of infection develop.
Patients should be instructed to contact their physician if persistent vomiting, diarrhea, signs of dehydration, cough or breathing difficulties occur, or signs of allergic reaction appear.
No specific cytochrome P450-based drug interaction studies have been conducted. No pharmacokinetic interaction between 85 mg/m2 ELOXATIN and infusional 5-FU has been observed in patients treated every 2 weeks. Increases of 5-FU plasma concentrations by approximately 20% have been observed with doses of 130 mg/m2 ELOXATIN dosed every 3 weeks. Since 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.
ELOXATIN should not be administered to patients with a history of known allergy to ELOXATIN or other platinum compounds.
Additional information about Eloxatin
Eloxatin Indication: Used in combination with infusional 5-FU/LV, is indicated for the treatment of advanced carcinoma of the colon or rectum and for adjuvant treatment of stage III colon cancer patients who have undergone complete resection of the primary tumor.
Mechanism Of Action: After activation oxaliplatin binds preferentially to the guanine and cytosine moieties of DNA, leading to cross-linking of DNA, thus inhibiting DNA synthesis and function.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Oxaliplatin
Synonyms: Oxaloplatino [Spanish]; Oxaloplatine [French]; Oxaliplatinum [Latin]; Oxaliplatino [Spanish]; Oxaliplatin [Usan:Inn:Ban]; Oxalatoplatinum; Oxalatoplatin
Drug Category: Antineoplastic Agents
Drug Type: Small Molecule; Approved; Investigational
Other Brand Names containing Oxaliplatin: DACPLAT; Eloxatin; Foloxatine; Transplatin; Elplat;
Absorption: Bioavailability is complete following intravenous administration.
Toxicity (Overdose): There have been five cases of oxaliplatin overdose reported. One patient received two 130 mg/m2 doses of oxaliplatin (cumulative dose of 260 mg/m2) within a 24-hour period. The patient experienced Grade 4 thrombocytopenia (<25,000/mm3) without any bleeding, which resolved. Two other patients were mistakenly administered oxaliplatin instead of carboplatin. One patient received a total oxaliplatin dose of 500 mg and the other received 650 mg. The first patient experienced dyspnea, wheezing, paresthesia, profuse vomiting and chest pain on the day of administration. She developed respiratory failure and severe bradycardia, and subsequently did not respond to resuscitation efforts. The other patient also experienced dyspnea, wheezing, paresthesia, and vomiting.
Protein Binding: Plasma protein binding of platinum (active metabolite) is irreversible and is greater than 90%.
Biotransformation: 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. There is no evidence of cytochrome P450-mediated metabolism in vitro.
Half Life: Approximately 10 - 25 minutes
Dosage Forms of Eloxatin: Powder, for solution Intravenous
Chemical IUPAC Name: (1R,2R)-cyclohexane-1,2-diamine; oxalate; platinum(+2) cation
Chemical Formula: C8H14N2O4Pt
Oxaliplatin on Wikipedia: https://en.wikipedia.org/wiki/Oxaliplatin
Organisms Affected: Humans and other mammals