Lyophilisate for solution for infusion.
In a bottle of 50 mg of lyophilisate. In a cardboard box 1 bottle.
Oxaliplatin is an antitumor drug belonging to a new class of platinum derivatives in which the platinum atom is complexed with oxalate and 1,2-diaminocyclohexane. Oxaliplatin exhibits a wide range of cytotoxic effects. It also exhibits in vitro and in vivo activity on various cisplatin-resistant tumor models. In combination with 5-fluorouracil, a synergistic cytotoxic effect is observed.
A study of the mechanism of action of oxaliplatin confirms the hypothesis that biotransformed, aqueous derivatives of oxaliplatin interacting with DNA by the formation of inter- and intra-traction bridges inhibit DNA synthesis, which leads to cytotoxicity and antitumor effect.
In vivo, oxaliplatin undergoes active biotransformation and does not show up in plasma by the end of 2 hours after administration at a dose of 130 mg / sq.m, with 15% of the administered platinum being in the blood and the remaining 85% being rapidly distributed to tissues or excreted by the kidneys . 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. In renal failure, there is a significant decrease in the clearance of oxaliplatin from 17.6 l / h to 9.95 l / h. The effect of severe renal failure on platinum clearance has not been studied.
Adjuvant therapy for colorectal cancer of stage III (C according to Duke) after radical resection of the primary tumor in combination with 5-fluorouracil and folinic acid
disseminated colorectal cancer (as monotherapy or combination therapy in combination with 5-fluorid acid) .
Hypersensitivity to oxaliplatin or other components of the
preparation myelosuppression (neutrophil count less than 2000 / Î¼l and / or platelet count less than 100000 / Î¼l) before the first course of treatment
peripheral sensory neuropathy with the first course of treatment with severe functional impairment impaired renal function (creatinine clearance less than 30 ml / min)
Use during pregnancy and lactation
Contraindicated in pregnancy and during lactation.
1 vial contains:
Active substances: oxaliplatin 50 mg.
Excipients: lactose monohydrate.
Dosage and administration
Intravenously as 2-6 hours of infusion. Hyperhydration with oxaliplatin is not required.
Applies to adults only.
The drug should be used immediately after preparation of the solution. When combined with 5-fluorouracil, oxaliplatin infusion should precede the administration of 5-fluorouracil.
Adjuvant therapy for colorectal cancer: 85 mg / m once every 2 weeks for 12 cycles (6 months).
Disseminated colorectal cancer: 85 mg / m2 once every 2 weeks as monotherapy or in combination with 5-fluorouracil.
Oxaliplatin is reintroduced only with neutrophils greater than 1,500 / Î¼l and platelets more than 50,000 / Î¼l.
Recommendations for dose adjustment and oxaliplatin administration regimen.
In case of hematologic abnormalities (the number of neutrophils <1500 / Î¼l and / or platelets <50,000 / Î¼l), the appointment of the next course is postponed until the laboratory parameters are restored. With the development of diarrhea of ââ4 degrees of toxicity (according to the WHO scale), neutropenia of 3-4 degrees (neutrophil count <1000 / Î¼l), thrombocytopenia 3-4 degrees (platelet count <50,000 / Î¼l), the dose of oxaliplatin should be reduced from 85 mg / m2 to 65 mg / m2 for the treatment of disseminated colorectal cancer and up to 75 mg / m2 for adjuvant therapy in addition to the usual dose reduction of 5-fluorouracil in case of their combined use. In patients who develop acute laryngeopharyngeal paresthesia during infusion or within a few hours after a 2-hour infusion, the next infusion of oxaliplatin should be carried out within 6 hours. Recommendations for adjusting the dose of oxaliplatin with development and neurotoxicity: with symptoms of neurotoxicity, causing pain lasting more than 7 days, the subsequent dose of oxaliplatin should be reduced from 85 mg / m2 to 65 mg / m2 for the treatment of disseminated colorectal cancer and to 75 mg / m2 for the adjuvant therapy with paresthesia without functional impairment, which persists until the next cycle, the subsequent dose of oxaliplatin should be reduced from 85 mg / m2 up to 65 mg / m for the treatment of metastatic colorectal cancer and up to 75 mg / m for the adjuvant therapy for paresthesia with functional impairment that persists until the next cycle, oxaliplatin should be discontinued with a decrease in expression nnosti symptoms after discontinuation of oxaliplatin neurotoxicity, you can consider resuming treatment. With the development of stomatitis and / or mucositis of the 2nd and more degree of toxicity, treatment with oxaliplatin should be suspended until they are stopped or symptoms of toxicity are reduced to 1 degree. Patients with renal failure There are no data on the use of oxaliplatin 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 Dosage adjustment is not required in patients with mild or moderate forms of liver failure. There are no data on the use of oxaliplatin in patients with severely impaired liver function. Elderly patients The safety profile of oxaliplatin as a monotherapy or when combined with 5-fluorouracil in patients over 65 years old is similar to that observed in patients under 65 years of age. Instructions for preparing a solution of . When preparing solutions and administering oxaliplatin, do not use needles or other equipment containing aluminum. 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 oxaliplatin (10 ml of solvent is introduced into a 50 mg vial, 20 mg into a 100 mg vial, and 30 ml into a 150 mg 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 0.2 to 0.7 mg / ml, while 0.7 mg / 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 saline solutions (sodium chloride solution) to dissolve the drug or dilute the drug solution (for preparing an infusion solution). Do not mix in one container, do not prescribe simultaneously with other drugs in the same infusion system (especially with 5-fluorouracil, basic solutions, trometamol and folinic acid preparations containing trometamol in their composition). Oxaliplatin may be given in conjunction with folinic acid infusions. In this case, the drugs should not be mixed in the same infusion tank. Folinic acid for infusion should be diluted with a 5% glucose solution, but in no case should you use solutions containing sodium chloride or alkaline solutions. The prepared solution of the preparation should be transparent and should not contain undissolved particles. Otherwise, the drug solution should not be used. A solution of the drug is used immediately after preparation. The drug is intended for single use only. Unused solution of the drug must be destroyed. The drug should be injected into the central venous line or into the peripheral vein within 2-6 hours. In case of extravasation, the administration of the drug should be stopped immediately. Materials, used for the preparation of the solution and its administration should be destroyed in accordance with the rules for the use of cytotoxic drugs. Side effects The most common side effects observed with oxaliplatin, including in combination with 5-fluorouracil / folinic acid, there were reactions from the gastrointestinal tract (diarrhea, nausea, vomiting, mucositis), hematological reactions (neutropenia, thrombocytopenia) and neurological reactions (acute and cumulative dose-dependent peripheral sensory neuropathy). In general, these side effects wouldwhether more frequent and more severe with a combination of oxaliplatin with 5-fluorouracil / folinic acid, compared with the use of only 5-fluorouracil and folinic acid. The frequency of adverse reactions below is set out in accordance with the following gradation: very often (> 1/10)
often (> 1/100, <1/10) infrequently (> 1/1000, <1/100) rarely (> 1/10000, <1/1000) very rarely (<1/10000), including individual messages. From the hemopoietic system: very often – anemia, leukopenia, neutropenia, thrombocytopenia, lymphopenia often – febrile neutropenia (including grade 3-4), sepsis with neutropenia rarely – hemolytic anemia, immune thrombocytopenia. From the digestive system: very often – nausea, vomiting, diarrhea, stomatitis, mucositis, pain in the stomach, constipation, loss of appetite often – dyspepsia, gastroesophageal reflux, hiccups infrequently – intestinal obstruction rarely – colitis, including cases of pseudomembranous colitis. From the central and peripheral nervous system: very often – peripheral neurosensory neuropathy, sensitivity disorders, headache, asthenia often – dizziness, meningism, depression, insomnia, infrequently – increased nervousness rarely – dysarthria. Neurotoxicity is a dose-limiting side effect. Symptoms of sensory neuropathy are often triggered by cold. The duration of these symptoms, which usually stop between the courses, increases depending on the total dose of oxaliplatin. Functional disorders, which are expressed by the difficulty in performing precise movements, are possible consequences of sensory damage. The risk of functional impairment for a total dose of about 850 mg / m2 (10 cycles) is about 10%, reaching 20% ââin the case of a total dose of 1020 mg / m2 (12 cycles). In most cases, neurological symptoms improve or completely disappear after discontinuation of treatment. However, in 3% of patients, 3 years after the end of treatment, either stable localized paresthesia of moderate intensity (2.3%) or paresthesia affecting functional activity (0.5%) was observed. During treatment with oxaliplatin, acute sensorineural manifestations were noted, which usually occurred within a few hours after administration of the drug and were most often provoked by cold. They were characterized by transient paresthesia, dysesthesia or hyposthesia, rarely (1-2%) with acute laryngeopharyngeal dysesthesia syndrome. The latter was manifested by a subjective feeling of dysphagia and shortness of breath without objective signs of respiratory distress syndrome (cyanosis or hypoxia), or laryngeal spasm or bronchospasm (without stridor or wheezing). Also observed were phenomena such as jaw spasm, tongue dysesthesia, dysarthria and a feeling of pressure in the chest. Typically, these symptoms quickly stopped both without the use of drug therapy, and with the introduction of antihistamines and bronchodilators. An increase in the infusion time during subsequent cycles of oxaliplatin therapy can reduce the frequency of this syndrome. From the musculoskeletal system: very often – back pain often – arthralgia, bone pain. On the part of the respiratory system: very often – cough, shortness of breath often – rhinitis, infections of the upper respiratory tract rarely – pulmonary fibrosis. From the cardiovascular system: often – pain behind the sternum, deep vein thrombophlebitis, pulmonary thromboembolism. From the urinary system: often – hematuria, dysuria. From the side of the skin and skin appendages: very often – alopecia, skin rashes often – peeling of the skin of the hands and feet, erythematous rashes, excessive sweating, irregularities in the nails. On the part of the organs of vision and hearing: often – conjunctivitis, visual impairment rarely – transient decrease in visual acuity, loss of visual fields, hearing loss, neuritis of the auditory nerve. Allergic reactions: rarely (with monotherapy) or often (in combination with 5-fluorouracil +/- calcium folinate) bronchospasm, angioedema, hypotension, and anaphylactic shock may occur. Often there have been cases of allergic manifestations such as a rash (especially urticaria), conjunctivitis or rhinitis. Local reactions: with extravasation of the drug, pain and inflammatory reactions at the injection site. On the part of laboratory indicators: very often – an increase in the level of alkaline phosphatase, activity of “liver” enzymes, the content of bilirubin, lactate dehydrogenase, hypokalemia, impaired sodium and glucose in the blood serum often – an increase in creatinine. Others: very often – increased body temperature, increased fatigue, increased body weight, taste disturbances. Drug Interaction Pharmaceutically incompatible with alkaline solutions and solutions containing chlorine. In cases of administration of a single dose of 85 mg / m2 oxaliplatin to patients immediately prior to administration of 5-fluorouracil, no change in 5-fluorouracil level was observed. No significant change in the binding of oxaliplatin to plasma proteins was observed in joint in vitro experiments with erythromycin, salicylates, granisetron, paclitaxel, and sodium valproate. Incompatibilities should not be used together with alkaline preparations or solutions (in particular, 5-fluorouracil, alkaline solutions, trometamol and folinic acid preparations, containing trometamol as an excipient) should not be used to dissolve the drug or dilute the drug solution (for the preparation of the infusion solution) saline solutions, do not mix with other drugs in one container or in the infusion system (do not use aluminum-containing injection equipment sedimentation and reduction of oxaliplatin activity). Overdose Symptoms: increased side effects described. Antidote not known. Treatment: Hematologic control and symptomatic therapy. Storage conditions Keep out of the reach of children and in a dark place at a temperature not exceeding 25 ° C. The Expiration of is 2.5 years. Active ingredient Oxaliplatin Terms of delivery from pharmacies Prescription dosage form dosage form infusion solution Medak GmbH, Germany