Xalipat-50/Xalipat-100

Oxaliplatin.

Each ml contains: Oxaliplatin BP 2 mg, Water for Injection BP qs. (See Table 1.)

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Excipients/Inactive Ingredients: Water for injection BP.

Pharmacotherapeutic group: Antineoplastic agent. ATC code: L01XA03.
Pharmacology: Oxaliplatin a cell phase nonspecific antineoplastic drug belongs to a new class of platinum agent that contains a platinum atom complexed with oxalate and diaminocyclohexane (DACH).
Mechanism of Action: The exact mechanism of action of oxaliplatin is not known. The mechanism of action of oxaliplatin is probably similar to that of cisplatin. Oxaliplatin forms reactive platinum complexes that are believed to inhibit DNA synthesis by forming interstrand and intrastrand cross-linking of DNA molecules. Oxaliplatin is not cross resistant to Cisplatin or Carboplatin, probably due to the DACH group and resistance to DNA mismatch repair. Oxaliplatin is a radiation sensitizing agent.
Pharmacokinetics: After intravenous distribution, Oxaliplatin is mainly accumulated in erythrocytes and does not diffuse into the plasma. 85-88% of platinum is protein bound in the first 5 hours after administration. Oxaliplatin undergoes rapid nonenzymatic biotransformation to reactive platinum complexes. The active metabolites of oxaliplatin are DACH platinum species. Oxaliplatin is excreted by renal excretion. Approximately 50% of the administered dose is excreted in the urine within the first 3 days. Fecal excretion is approximately 0.5% per day and reaches 5% of the total dose by day 11. The terminal half-life of ultra-filterable platinum (Oxaliplatin and free Oxaliplatin metabolites) is 273±19 hrs. The platinum elimination from the erythrocytes takes about 48 days.

Oxaliplatin is indicated in the treatment of metastatic colorectal cancer after failure of treatment with fluoropyrimidines, alone by monochemotherapy or along with fluoropyrimidines.

As single agent: When used alone, the recommended dose of Oxaliplatin is 130 mg/m² as a continuous intravenous infusion over 2 to 6 hours. The dose may be repeated at an interval of 3 weeks.
In combination therapy: IV: On day 1, administer oxaliplatin 85mg/m² concurrently with leucovorin 200 mg/m² (in separate containers using a Y line) by IV infusion over 2 hours. Then administer fluorouracil 400 mg/m² by IV injection over 2 to 4 minutes, followed by fluorouracil 600 mg/m² by IV infusion over 22 hours.
On day 2, administer leucovorin 200mg/m² by IV infusion over 2 hours. Then administer fluorouracil 400 mg/m² by IV injection over 2 to 4 minutes, followed by fluorouracil 600 mg/m² by IV infusion over 22 hours. Repeat regimen at intervals of 2 weeks. (See Table 2.)

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Do not administer next dose until neutrophil count is > 1500 / mm³ and platelet count > 75.000 /mm³.
Renal Impairment: In patients with impaired renal function, observe caution.
Monitoring Parameters: Asses the patient for differential WBC count, hemoglobin, platelet count and ALT, AST, bilirubin and creatinine levels before each Xalipat cycle.

There is no known antidote for oxaliplatin over dosage. In general, supportive care and frequent monitoring of vital signs should be administered.

Oxaliplatin is contraindicated in patients with: History of severe allergy to the drug; Severe pre-existing peripheral neuropathy; Severe renal dysfunction (CrCl<30ml/min); Pregnancy and breast feeding.

Oxaliplatin should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents.
Aluminium has been reported to cause degradation of platinum compounds and hence needles or intravenous administration sets containing aluminium parts that may come in contact with oxaliplatin should not be used for the preparation or mixing of the drug.
Oxaliplatin should not be administered undiluted. Dilute with 5% Dextrose infusion.
Oxaliplatin should not be mixed with any other medication and it should not be administered simultaneously by the infusion line.
Caution is recommended while administering oxaliplatin to patients with known hypersensitivity to other platinum agents.
Oxaliplatin is incompatible in solution with alkaline medications or media and hence it is advised that oxaliplatin should never be diluted with Sodium Chloride / Chloride containing infusion solutions.
Oxaliplatin has been found to be mutagenic in mammalian in vitro mutation chromosome test. Although carcinogenic studies have not been done. Oxaliplatin is considered probable carcinogen.
Oxaliplatin is embryotoxic in rats. Oxaliplatin may cause fetal harm when administered to pregnant women. The patient should be apprised of potential hazard to the fetus and potential risk for loss of the pregnancy if there is exposure to oxaliplatin during pregnancy.
It is not known whether oxaliplatin is excreted in human milk or not. Caution should be exercised when oxaliplatin is administered to a nursing woman as many drugs are excreted in human milk.
Inspect the solution visually for particulate matter and discolouration prior to administration.
Effects on ability to drive and use machine: Not known.

Oxaliplatin is embryotoxic in rats. Oxaliplatin may cause fetal harm when administered to pregnant women. The patient should be apprised of potential hazard to the fetus and potential risk for loss of the pregnancy if there is exposure to oxaliplatin during pregnancy.
It is not known whether oxaliplatin is excreted in human milk or not. Caution should be exercised when oxaliplatin is administered to a nursing woman as many drugs are excreted in human milk.

Commonly occurring adverse effects of Oxaliplatin are: Sensory neuropathy (dose limiting toxicity); Anaemia; Fever; Nausea & vomiting; Liver function abnormalities; Infections; Alopecia; Pharyngolaryngeal dysesthesia.
Other side effects that become more pronounced when used in combination with fluorouracil and leucovorin are: Neutropenia; Thrombocytopenia; Diarrhoea; Mucositis.

Oxaliplatin induces irinotecan-related cholinergic syndrome by potentiating irinotecan inhibition of acetylcholinesterase. Oxaliplatin has no influence on fluorouracil and topotecan pharmacokinetics. Preclinical studies have shown oxaliplatin to be synergistic with fluorouracil and SN-38, the active metabolite of irinotecan.
There are no other studies documenting any major interactions of oxaliplatin with other drugs.

Incompatibilities: None.

To be stored at a temperature below 25°C. Protect from light. Do not freeze.
Shelf life of the medicinal product as package for sale: 24 Months.

Cytotoxic Chemotherapy

L01XA03 - oxaliplatin ; Belongs to the class of platinum-containing antineoplastic agents. Used in the treatment of cancer.

POM

Xalipat-50: Inj (vial) 50 mg/50 mL x 1's.
Xalipat-100: Inj (vial) 100 mg/50 mL x 1's.