Index of drugs

In adults, to induce remission of acute myeloid leukemia and in adults and children to induce remission of other acute leukemias.

1 ml of solution to shock and inf. contains 100 mg of cytarabine.

Anticancer drug - antimetabolite - pyrimidine analogue. Cytarabine inhibits DNA synthesis in the S phase of the cell cycle. It also has antiviral and immunosuppressive properties. Detailed studies on the mechanism of cytotoxicityin vitro indicate that the primary action of cytarabine is the inhibition of deoxycytidine synthesis through the active metabolite 5-cytarabine triphosphate (ARA-CTP), although cytitabine kinase inhibition and the incorporation of cytarabine into nucleic acid molecules may play a role in its cytostatic and cytocidal activity. The high dose cytarabine dose regimen is able to overcome the resistance of non-responder leukemic cells using conventional doses. Several mechanisms are responsible for the resistance of cells: increasing the amount of substrate; increasing the intracellular pool of ARA-CTP, there is a positive correlation between the intracellular ARA-CTP retention and the percentage of cells in the S-phase. Cytarabine undergoes deamination to arabinofuranosyluracil in the liver and kidneys. After intravenous administration in humans, only 5.8% of the dose is excreted unchanged in the urine within 12-24 h; 90% of the dose is excreted as an inactive deamination product - arabinofuranosyl uracil (ARA-U). Cytarabine is metabolised quickly, mainly in the liver and possibly in the kidneys. After administration of single intravenous doses, the majority of patients within 15 min reduce their blood levels to unmeasurable levels. T_0,5 is 10 minutes. Maximum concentration of cytarabine in the serum at high doses is 200 times higher compared to the concentration when using conventional doses. The highest concentration of the inactive ARA-U metabolite at high doses is observed already after 15 min. The renal clearance of cytarabine is lower when high doses are used compared to conventional doses. Cytarabine concentration in cerebrospinal fluid (CSF) after intravenous administration of high-dose cytarabine 1-3 g / m²is about 100-300 nanograms / ml. Following subcutaneous administration of cytarabine, peak plasma concentrations are obtained approximately 20-60 min after administration and are significantly lower than the corresponding concentrations obtained after intravenous administration.

Hypersensitivity to cytarabine or to any of the excipients. Anemia, leukopenia and thrombocytopenia with non-benign etiology (eg, bone marrow aplasia) and if the doctor does not find that this treatment is the most optimistic alternative to the patient. Degenerative and toxic encephalopathies, especially after Methotrexate or treatment with ionizing radiation.

Cytarabine strongly inhibits bone marrow function; treatment should be started with caution in patients with previous drug-induced marrow suppression. If blast cells disappear from the peripheral blood image, bone marrow tests should be performed frequently. Treatment discontinuation or adjustment should be considered if the platelet count is reduced to less than 50,000 due to drug-induced marrow suppression or the granulocyte count falls below 1000 / mm³. The number of peripheral blood morphing elements may continue to decrease after discontinuation of therapy, reaching the lowest value 5-7 days after the end of drug administration. If there are indications, treatment should be re-introduced after the appearance of clear signs of bone marrow improvement (results of subsequent bone marrow tests). Patients who have been discontinued until their "normal" morphing values ​​of peripheral blood components may not be sufficiently controlled. In adult patients with acute non-lymphocytic leukemia, after the application of a therapy combining large doses of cytarabine, daunorubicin and asparaginase, there were peripheral motor and sensory neuropathies.Patients treated with high doses of cytarabine should be monitored for signs of neuropathy, as changes in the treatment regimen may be necessary to avoid persistent neurological disorders. Heavy, and sometimes fatal cases of lung toxicity, adult respiratory distress syndrome and pulmonary edema have occurred with high doses of cytarabine. During treatment with cytarabine, anaphylactic reactions have been reported. In animal studies, cytarabine has been shown to be carcinogenic; the risk of similar activities in humans should be taken into account, choosing a strategy for long-term treatment of the patient. In patients treated with conventional doses of cytarabine in combination with other medicines, abdominal (peritonitis) and gay encephalitis with associated neutropenia and thrombocytopenia were reported. Patients respond well to conservative (non-surgical) treatment. In children with acute myeloid leukemia (AML) after intravenous administration of conventional doses of cytarabine in combination with other drugs, development of delayed, progressive, ascending paralysis followed by death was observed. Liver and kidney function should be investigated during treatment with cytarabine. In patients with existing hepatic impairment, the drug should be used with extreme caution. Patients receiving cytarabine should periodically check bone marrow, liver and kidney function. As with other cytotoxic drugs, the use of cytarabine may lead to increased uric acid levels in the blood as a result of the breakdown of neoblast cells, and regular monitoring of blood uric acid levels. If necessary, pharmacological supportive measures may be used to control hyperuricemia. Administration of live or live attenuated vaccines to patients with impaired immunization due to the use of chemotherapy, including cytarabine, can lead to serious infections and even death. Patients receiving cytarabine should not be vaccinated with live vaccines. Dead or inactivated vaccines may be administered, bearing in mind that the immune response to such vaccines may be impaired. The risk of adverse reactions from o.u.n. increases in patients who have received previous treatment o.u.n. such as: intrathecal chemotherapy, radiotherapy. If severe respiratory insufficiency is reported, concomitant granulocyte transfusion should be avoided. There have been reports of death-related cardiomyopathies after application of experimental therapy with high doses of cytarabine combined with cyclophosphamide in the preparation of patients for bone marrow transplantation. The safety of the medicine in infants has not been established. One dose contains less than 1 mmol sodium (23 mg) - the medicine can be considered "free" from sodium.

Cytarabine should be used in pregnant women or women who could become pregnant only if the expected benefits outweigh the potential risk to the fetus. During treatment and for 6 months after its completion, it is necessary to use effective methods of contraception by women and men treated with cytarabine. It is known that cytarabi is teratogenic in some animal species. The drug should not be used in pregnant women or nursing mothers. Reproductive toxicity studies with cytarabine have not been performed. Patients treated with cytarabine in combination with alkylating preparations may experience suppression of the function of the gonads, causing amenorrhea or azoospermia. In general, the occurrence of these side effects is related to the dose and length of treatment. Side effects can be permanent. Cytarabine is mutagenic, which can cause chromosomal damage in human reproductive cells, so that both women and men undergoing treatment with cytarabine should be instructed to use effective methods of contraception.

Common: anemia, megaloblastosis, leukopenia, thrombocytopenia, anorexia, hyperuricaemia, nervous system disorders after high doses of cytarabine (side effects affectingcerebral and cerebellum with depression, dysarthria, nystagmus), transient hemorrhagic conjunctivitis (photophobia, burning pain, visual disturbances, increased tearing), keratitis, dysphagia, abdominal pain, nausea, vomiting, diarrhea, inflammation or mouth ulcers and (or) anus, transient liver effects with increased liver enzymes, transient side effects on the skin (erythema, bullous lesions, urticaria, vasculitis, alopecia), renal dysfunction, urinary retention, fever, thrombophlebitis at the injection site. Uncommon: sepsis (immunosuppression), cellulitis at the injection site, pigmented spot (lentigo), headache, peripheral neuropathy, pericarditis, pneumonia, shortness of breath, sore throat, oesophagitis, oesophageal ulcer, intestinal chorinal malwater, necrotizing inflammation colitis, peritonitis, skin ulcer, pruritus, burning pain in the hands and soles of the feet, muscle pain, joint pain. Very rare: Arrhythmia, neutrophil gland inflammation of the eccrine sweat gland. Following the administration of rapid intravenous injections, patients often have nausea and vomiting, which may persist for several hours. These complaints are generally less pronounced when the medicine is given by infusion. After 6-12 hours of starting treatment, the cytarabin syndrome may occur (fever, muscle pain, bone pain, sporadic chest pain, rash, conjunctivitis and nausea). Corticosteroids may be used to prevent and treat the cytarabine syndrome. Cases of cardiomyopathy and rhabdomyolysis have been reported following treatment with cytarabine. There was one case of anaphylaxis that led to cardiac arrest requiring resuscitation. The effect occurred directly after intravenous administration of cytarabine.

Intravenously (in the form of infusions or injections) as well as subcutaneously (subcutaneous injection is generally well tolerated and may be recommended for use in maintenance therapy). Do not administer the drug intrathecally. Treatment with cytarabine should be initiated by, or after consultation with, a physician experienced in the use of cytostatic preparations.Remission induction.The dose and the induction dosing regimen vary depending on the treatment regimen used.Continuous treatment. The following treatment regimens have been used in the induction of remission in continuous treatment:1 scheme - quick injection - the usual starting dose for 10 days is 2 mg / kg / day, the number of blood cells should be checked every day; in the absence of anti-leukemic effects and visible toxicity, the dose should be increased to 4 mg / kg / day and maintained until treatment is responding to or manifestation of obvious toxicity; almost all patients may experience toxicity after the above dose of cytarabine;2 diagram - 0.5-1.0 mg / kg / day may be given as an infusion lasting up to 24 hours; in the majority of patients the results obtained after a one-hour infusion were satisfactory; after 10 days, the daily starting dose may be increased to 2 mg / kg. subject to toxicity, treatment with the above dose may be continued until remission or toxicity occurs.Periodic treatment. In the induction of remission in bipolar treatment, the following treatment regimens were used:1 scheme - a dose of 3-5 mg / kg / day is administered intravenously over 5 consecutive days, after a 2-9 day interval, the Next treatment cycle is given; treatment should be continued until remission or toxicity, the first signs of bone marrow improvement were reported at 7-64 days (mean day 28) from the start of treatment; if the patient has not experienced any signs of toxicity or remission after using the correct clinical trial, a cautious administration of a higher dose is generally warranted (patients are found to tolerate higher doses when cytarabine is given by bolus injection into a vein than by slow infusion);2 diagram - cytarabine was used as a continuous infusion for 5-7 days, at a dose of 100-200 mg / m²/ day, both as monotherapy and in combination therapy with other cytotoxic drugs, e.g. anthracyclines; additional chemotherapy cycles may be given at intervals of 2 to 4 weeks until remission or unacceptable toxicity occurs.Maintenance treatment. The size of the dose and the maintenance dosage regimen vary depending on the treatment regimen used. After remission in continuous treatment, the following treatment regimens were used:1 scheme - remissions induced by cytarabine or other preparations may be sustained by the use of cytarabine by intravenous or subcutaneous injection at a dose of 1 mg / kg. once or twice a week;2 diagram- cytarabine is also administered in doses of 100-200 mg / m², continuously infused for 5 days at monthly intervals, in monotherapy or in combination with other cytotoxic preparations.Large doses. Cytarabine under close medical supervision can be used in monotherapy, as well as in combination with other cytotoxic preparations at a dose of 2 to 3 g / m² administered as an intravenous infusion lasting from 1-3 h, used every 12 h for 2-6 days (a total of 12 doses per cycle). Do not use a dose higher than the total therapeutic dose, 36 g / m². The frequency of treatment cycles depends on the response to treatment and the haematological and non-haematological toxicity. In patients with impaired liver and kidney function, the dose should be reduced. Cytarabine undergoes dialysis - the drug should not be administered immediately before or after dialysis. In patients over 60 years of age, treatment with high doses should only be used after careful risk / performance evaluation.