Oxaliplatin

BRAND NAMES

Eloxatin: Eloxatin includes the active components of oxaliplatin. It is offered as an intravenous infusion to treat colon cancer. It is a platinum-based medication used in conjunction with inffusional fluorouracil and leucovorin for the adjuvant treatment of stage III colon cancer in patients who have had total resection of the main tumor, as well as for advanced colorectal cancer.

MECHANISM OF ACTION

Oxaliplatin is an alkylating agent with non-cell cycle-specific cytotoxicity. The platinum complex of the medication attaches to DNA, forming cross-links. Cross-links hinder DNA replication, transcription, and cell cycle arrest, culminating in cell death. It has a synergistic effect with fluoropyrimidines like 5-fluorouracil. Oxaliplatin is useful in treating fast-growing cancers such as those in the gastrointestinal tract, which have a high cell turnover rate.

PHARMACOKINETICS

Absorption

Oxaliplatin is biotransform into aquated forms in the blood, where three species are present. Total platinum is ultra-filterable or free, as is erythrocyte platinum. Flameless atomic absorption is used to determine platinum concentrations in diverse tissues.

Distribution

The mean volume of distribution of oxaliplatin is 440 L/kg.

Metabolism

Oxaliplatin undergoes nonenzymatic conversion to active derivatives in physiological solution by displacing the labile oxalate ligand. Several transitory reactive species are produced, including monocoque and diaquo DACH platinum, which form covalent bonds with macromolecules.

Excretion

Approximately 50% of oxaliplatin is excreted through urine and the other 2% through feces.

PHARMACODYNAMICS

Oxaliplatin, when combined with fluorouracil, has more antiproliferative action in vitro and in vivo than either chemical alone in a variety of tumor types, including mammary and leukemia. Oxaliplatin has been proven in vivo to have anti-tumor activity against colon cancer.

DOSAGE AND ADMINISTRATION

Oxaliplatin comes as a solution that can be injected into the vein. Oxaliplatin is administered by a physician or nurse. It is usually given once every fourteen days.

It is available in the form of powder for injectable solutions with the strengths of 50 mg, 100 mg, and 200 mg/vial.

DRUG INTERACTIONS

Drug interactions with oxaliplatin may include

• Anti-arrhythmic drugs: quinidine, disopyramide, procainamide, lidocaine, mexiletine, flecainide, and propafenone.
• Anti-coagulants: warfarin

CONTRAINDICATIONS

Contraindications of oxaliplatin in patients who have severe renal impairment, posterior reversible encephalopathy syndrome, or rhabdomyolysis.

SIDE EFFECTS

Oxaliplatin may cause side effects

• Pain in the hands
• Decreased sense of touch
• Increased sensitivity
• Vomiting
• Nausea
• Constipation
• Loss of appetite
• Stomach pain
• Heartburn
• Dry mouth
• Tiredness
• Depression
• Anxiety
• Dry skin
• Flushing

Some serious side effects may include

• Difficulty speaking
• Loss of balance
• Cough
• Pain when urinating
• Chest pain
• Decreased urination
• Blood in urine
• Weakness
• OVERDOSE
• Symptoms of overdose may include
• Shortness of breath
• Wheezing
• Vomiting
• Chest pain
• Slowed breathing
• Diarrhea
• Numbness in the finger

TOXICITY

No known antidote exists for oxaliplatin overdose. Oxaliplatin has dose-dependent toxicity in the hematopoietic system. It causes myelosuppression, anemia, and thrombocytopenia. In rare cases with repeated oxaliplatin treatment, hypersensitivity reactions, hemolytic anemia, and secondary immune thrombocytopenia can occur. Oxaliplatin has dose-limiting toxicity on the nervous system. It can cause acute or chronic peripheral neuropathy. The therapy is discontinuation and symptomatic management.