Description
Latin name
OXALIPLATIN-EBEWE
Release form
Lyophilisate for solution for infusion.
Packing
In a bottle of 50 mg of lyophilisate. In a cardboard box 1 bottle.
Pharmacological action
Pharmacodynamics
An antitumor drug belonging to a new class of platinum-based compounds in which the platinum atom forms a complex bond with 1,2-diaminocyclohexane (DACG) and the oxalate group.
Oxaliplatin has antitumor activity in various types of tumors, including colorectal cancer. It is also effective in the treatment of cisplatin-resistant tumors. The action is manifested regardless of the phase of the cell cycle. When used with 5-fluorouracil, a synergistic cytotoxic effect is observed. The mechanism of the antitumor effect of oxaliplatin is based on the cytotoxic effect and is not fully understood. Presumably, oxaliplatin forms inter- and intra-linkages with DNA, thereby inhibiting the phases of its replication and transcription.
Pharmacokinetics of
In vivo, oxaliplatin undergoes active biotransformation and is not detected in plasma by the end of 2 hours after administration at a dose of 130 mg / m2, with 15% of the administered platinum in the blood and the remaining 85% quickly distributed in the tissues or excreted by the kidneys.
In vitro biotransformation is the result of non-enzymatic degradation, and there is no evidence that oxaliplatin is metabolized by cytochrome P450. Oxaliplatin undergoes extensive metabolism, while the drug is not found in plasma ultrafiltrate after a 2-hour infusion. Some cytotoxic decomposition products of oxaliplatin, including Platinum monochloro-, dichloro- and quadro-diaminocyclohexane are found in blood plasma together with inactive conjugates at a later date of the study.
Platinum binds to plasma albumin and is excreted in the urine during the first 48 hours. By day 5, about 54% of the entire dose is found in urine and less than 3% in feces.
Pharmacokinetics in special clinical cases
The effect of renal dysfunction on the distribution of oxaliplatin was studied in patients with varying degrees of renal dysfunction. Oxaliplatin was administered at a dose of 85 mg / m2 in the control group with normal renal function (CC more than 80 ml / min), in patients with minor (CC from 50 to 80 ml / min) and moderate impaired renal function (CC from 30 to 49 ml / min) and at a dose of 65 mg / m2 in patients with severe renal failure (CC less than 30 ml / min). It was found that excretion of oxaliplatin significantly correlates with CC. Renal clearance of platinum was reduced in patients by 30%, 65% and 84% with mild, moderate and severe renal impairment, respectively, compared with patients with normal renal function.
Indications
Adjuvant therapy of stage III colorectal cancer (C according to Duke) after radical resection of the primary tumor in combination with 5-fluorouracil and calcium folinate
disseminated colorectal cancer (as monotherapy or combination therapy in combination with 5-fluorine)
ovarian cancer (as a second-line therapy).
Contraindications
Myelosuppression before the first course of therapy with neutrophils less than 2000 / μl and / or platelets less than 100,000 / μl
peripheral sensory neuropathy with functional impairment before the first course of
expressed renal impairment / min less than 30 min K )
pregnancy
lactation (breastfeeding)
childhood
hypersensitivity to oxaliplatin, other platinum derivatives or other components of the drug.
Caution: the drug should be prescribed for impaired renal function, rare hereditary forms of lactose intolerance, lactase deficiency or malabsorption of glucose / galactose (because the composition contains lactose).
Use during pregnancy and lactation
Oxaliplatin-Ebeve should not be used during pregnancy.
No controlled studies of doxorubicin use in pregnant women have been conducted. Animal studies have shown the embryotoxic, teratogenic and mutagenic effects of oxaliplatin. Therefore, oxaliplatin should not be prescribed to pregnant women.
It is not known whether oxaliplatin passes into breast milk, therefore, to avoid the potential toxic effect of the drug on the baby, breastfeeding should be discontinued during treatment.
Composition
1 vial contains:
Active substances: oxaliplatin 50 mg.
Excipients: lactose monohydrate – 450 mg.
Dosage and administration of
Oxaliplatin-Ebeve is prescribed only for adults in the form of iv infusion for 2-6 hours.
Hyperhydration is not required when using the drug. If oxaliplatin is used in combination with 5-fluorouracil, oxaliplatin infusion should precede the administration of 5-fluorouracil.
Adjuvant therapy for colorectal cancer – 85 mg / m2 once every 2 weeks for 12 cycles (6 months).
Treatment of metastatic colorectal cancer – 85 mg / m2 once every 2 weeks as monotherapy or in combination with 5-fluorouracil.
Ovarian cancer treatment – 85 mg / m2 once every 2 weeks as monotherapy or in combination with other chemotherapeutic drugs.
Repeated injections of Oxaliplatin-Ebewe only produce neutrophils> 1,500 / μl and platelets> 50,000 / μl.
Recommendations for dose adjustment and administration of oxaliplatin
In case of hematologic abnormalities (neutrophil count <1500 / μl and / or platelet count <50,000 / μl), the next course is postponed until normal laboratory parameters are restored. With the development of diarrhea of 4 degrees of toxicity (according to the WHO scale), neutropenia of 3-4 degrees (neutrophil count <1000 / μl), thrombocytopenia of 3-4 degree (platelet count <50,000 / μl), the dose of Oxaliplatin-Ebewe should be reduced with subsequent administrations from 85 mg / m2 to 65 mg / m2 for the treatment of disseminated colorectal cancer and ovarian cancer to 75 mg / m2 for the adjuvant therapy for colorectal cancer in addition to the usual dose reduction of 5-fluorouracil in case of their combined use. In patients who develop acute laryngeopharyngeal dysesthesia during the infusion or within a few hours after a 2-hour infusion, the next infusion of Oxaliplatin-Ebeve should be performed within 6 hours. In case of pain (as a sign of neurotoxicity) lasting more than 7 days or with paresthesia without functional impairment that persists until the next cycle, the subsequent dose of Oxaliplatin-Ebeve should be reduced from 85 mg / m2 to 65 mg / m2 (in the treatment of metastatic cancer) or up to 75 mg / m2 (with adjuvant therapy). With paresthesia with functional impairment, which persists until the next cycle, the drug Oxaliplatin-Ebewe should be canceled with a decrease in the severity of symptoms of neurotoxicity after the abolition of oxaliplatin, you can consider resuming treatment. With the development of stomatitis and / or mucositis of the 2nd or more degree of toxicity, treatment with Oxaliplatin-Ebeve should be suspended until they are stopped or the manifestations of toxicity are reduced to 1 degree. Patients with impaired renal function The drug should not be used in patients with severe renal impairment. Due to the limited data on the safety and tolerability of the drug in patients with a moderate degree of impaired renal function, the benefit / risk ratio for the patient should be weighed before using the drug. Therapy in this category of patients can be started with the recommended dose, under close monitoring of renal function. With a mild degree of impaired renal function, dose adjustment of oxaliplatin is not required. Patients with impaired liver function Changing the dosage regimen in patients with mild or moderate impaired liver function is not required. There are no data on the use of oxaliplatin in patients with severely impaired liver function. Elderly patients Dosage adjustment is not required when using oxaliplatin in patients over 65 years of age (including when used in combination with 5-fluorouracil). Rules for the preparation and administration of the solution. Needles and other equipment containing aluminum must not be used in the preparation and administration of oxaliplatin. Before use, the drug is dissolved in water for injection or in a 5% dextrose solution, obtaining a solution with a concentration of 5 mg / ml of oxaliplatin (10 ml of solvent is introduced into a 50 mg vial, 100 mg of 20 ml of solvent into a vial). Reconstituted in this way, the drug is immediately diluted with 250-500 ml of 5% dextrose solution. The concentration of the resulting oxaliplatin solution should be from 200 μg / ml to 700 μg / ml, while 700 μg / ml is the highest concentration, used in clinical practice at a dose of 85 mg / m2. Only recommended solvents should be used to prepare the solution. Do not use the drug undiluted. Do not use 0.9% sodium chloride solution or other saline solutions to dissolve the drug or dilute the drug solution (for preparing an infusion solution). Should not be mixed in one container and administered simultaneously in the same infusion system with other drugs (especially 5-fluorouracil, alkaline solutions, trometamol and calcium folinate preparations containing trometamol in their composition). Oxaliplatin may be given in conjunction with calcium folinate infusions. In this case, the drugs should not be mixed in the same container for infusion. Calcium folinate for infusion should be diluted with a 5% dextrose solution, but in no case should you use solutions containing sodium chloride or alkaline solutions. A solution of the drug for infusion is recommended to be used immediately after preparation. The reconstituted infusion solution remains stable for 24 hours at room temperature (not higher than 25 ° C). The prepared solution of the preparation should be transparent and should not contain undissolved particles. The solution with signs of precipitation must be destroyed. In case of extravasation, the administration of the drug should be stopped immediately. Drug Interaction There was no significant change in the binding of oxaliplatin to blood plasma proteins when co-administered with erythromycin, salicylates, granisetron, paclitaxel, and valproic acid. Sedimentation and reduction of oxaliplatin activity may occur upon interaction with aluminum. No single changes in serum 5-fluorouracil concentrations were observed with single / in the administration of oxaliplatin at a dose of 85 mg / m2, immediately prior to administration of 5-fluorouracil. Pharmaceutical Interaction The drug is pharmaceutically incompatible with alkaline solutions and solutions containing chlorides. Do not mix with alkaline drugs or solutions, especially fluorouracil and folinate calcium preparations, containing trometamol as an adjuvant, and with other active substances in the form of salts of trometamol. Overdose Symptoms: myelosuppression, neurotoxicity, diarrhea, nausea, vomiting. Treatment: Hematologic control and symptomatic therapy. The antidote to oxaliplatin is unknown. Storage conditions Keep out of the reach of children at a temperature not exceeding 25 ° C. Expiration 3 years. Deystvuyuschee substances oxaliplatin Terms of delivery from pharmacies Prescription dosage form dosage form infusion solution
