Description
Pharmacological action
Antitumor agent, a derivative of platinum. Oxaliplatin is a stereoisomer in the molecule of which the central atom of platinum is surrounded by oxalate and diaminocyclohexane located in trans positions. Like other platinum derivatives, oxaliplatin interacts with DNA, forming intra- and inter-helix cross-linking, which blocks its synthesis and subsequent replication. The synthesis of oxaliplatin-DNA bonds is fast and lasts for a maximum of 15 minutes (in cisplatin this process is biphasic with a delayed 4-8-hour phase). Violation of DNA synthesis leads to inhibition of the synthesis of RNA and cellular protein. Oxaliplatin is effective on some cisplatin-resistant lines.
Pharmacokinetics
Oxaliplatin is extensively metabolized and by the end of 2-hour administration at a dose of 130 mg / m2 it is no longer detectable, with 15% of the administered dose being in the blood and the remaining 85% is rapidly distributed in the tissues (or excreted in the urine). Platinum binds to plasma albumin.
Excreted in urine during the first 48 hours.
By the fifth day, about 54% of the total dose is found in urine and less than 3% in feces.
In renal failure, a significant decrease in clearance was observed from 17.55 В± 2.18 l / h to 9.95 В± 1.91 l / h and Vd from 330 В± 40.9 to 241 В± 36.1 l. The effect of severe renal failure on platinum clearance has not been studied.
Indications
Metastatic colorectal cancer as a monotherapy or as part of combination therapy with fluoropyrimidines.
Ovarian cancer.
Contraindications
Myelosuppression before the first course of therapy with neutrophils less than 2 × 109 / L and / or platelets less than 100 × 109 / L, peripheral sensory neuropathy before the first course of treatment, severe renal impairment (CC less than 30 ml / min ), pregnancy, lactation (breastfeeding), hypersensitivity to oxaliplatin.
Recommendations for the use of
Set individually, depending on the indications and stage of the disease, the state of the hematopoietic system, the anti-tumor therapy regimen.
Special instructions
Oxaliplatin can only be used by a qualified doctor who has experience in conducting antitumor chemotherapy.
Before starting treatment and before the next administration of oxaliplatin, it is necessary to conduct a study of peripheral blood, in addition, a neurological examination should be performed regularly, especially when used with drugs with potential neurotoxicity.
The use of antiemetics is recommended for the prevention and treatment of nausea and vomiting.
In cases of hematological disorders (leukopenia less than 2 Г— 109 / l and / or thrombocytopenia less than 50 Г— 109 / l), the next administration should be postponed until the normal blood picture is restored.
Composition
1 ml contains:
Active substances: oxaliplatin – 5 mg,
Excipients: lactose monohydrate – 45 mg, water d / and – up to 1.
Side effects
From the hemopoietic system: anemia, leukopenia, granulocytopenia, thrombocytopenia.
From the digestive system: nausea, vomiting, diarrhea.
From the side of the central nervous system and peripheral nervous system: often – peripheral neuropathies, characterized by paresthesia of the limbs may be accompanied by seizures, dysesthesia of the perioral region or upper respiratory tract (which can simulate the clinical picture of reversible laryngospasm) and gastrointestinal tract. The appearance of such symptoms is often due to exposure to cold. Paresthesia mainly regresses between courses of treatment, however, it can become permanent and cause functional impairment usually after exceeding a total dose of 800 mg / m2 (6 courses).
Other: in some cases – fever, skin rash.
Terms of delivery from
pharmacies Prescription
dosage form
infusion solution