Cytarabine (Cytarabinum)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

Antineoplastic agents

Antimetabolites

Included in the formulation
  • Alexan®
    solution for injections 
    Ebewe Pharma Gesmb.b. Nfg. KG     Austria
  • Cytarabine
    lyophilizate for injections 
    BELMEDPREPARATY, RUP     Republic of Belarus
  • Cytarabine-LENS®
    lyophilizate for injections 
    LENS-PHARM, LLC     Russia
  • Cytosar®
    lyophilizate for injections 
    Pfizer Inc.     USA
  • Cytostadine
    solution for injections 
    SHTADA Artznajmittel AG     Germany
    • Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

    VED

    АТХ:

    L.01.B.C.01   Cytarabine

    Pharmacodynamics:

    Antitumor agent from the group of antimetabolites - analogues of pyrimidine. It is assumed that cytarabine acts by inhibiting the DNA polymerase. In addition, it seems that it is boundedly included in DNA and RNA.

    Pharmacokinetics:

    With rapid intravenous injection cytarabine only in moderate amounts penetrates the blood-brain barrier, but after continuous intravenous infusion the concentration in the cerebrospinal fluid reaches 40-50% of the steady-state concentration in the plasma. Binding to proteins is 15%. Rapidly metabolized by deamination in the blood and tissues, especially in the liver, and in minimal amounts in the cerebrospinal fluid.

    Half-life characterized by individual differences.It is excreted by the kidneys, less than 10% - unchanged.

    Indications:

    Acute non-lymphoblastic leukemia, blast crisis of chronic myelogenous leukemia, lymphogranulomatosis, erythromyelosis, neiroleukemia, non-Hodgkin's lymphomas.

    ICD-10

    II.C81-C96.C92.9   Myeloid leukemia, unspecified

    II.C81-C96.C92.1   Chronic myeloid leukemia

    II.C81-C96.C92.0   Acute myeloid leukemia

    II.C81-C96.C91.9   Lymphoid leukemia, unspecified

    II.C81-C96.C91.0   Acute lymphoblastic leukemia

    II.C81-C96.C81   Hodgkin's disease [lymphogranulomatosis]

    II.D37-D48.D46   Myelodysplastic syndromes

    II.C81-C96.C85.9   Non-Hodgkin's lymphoma, unspecified

    Contraindications:

    Myelodepression, pregnancy, hypersensitivity to cytarabine.

    Do not recommend applying cytarabine in patients with chickenpox (including recently transferred or after contact with the diseased), with herpes zoster or other acute infectious diseases.

    Carefully:

    Use with caution cytarabine in patients with oppression of the hematopoietic system, impaired renal and / or liver function (due to an increased risk of developing neurotoxicity, especially in high-dose therapy), with bone marrow infiltration by tumor cells,with diseases with an increased risk of developing hyperuricemia (gout or urate nephrolithiasis), as well as in patients who received previously cytotoxic drugs or radiotherapy.

    In elderly patients, a dose reduction may be required (age-related renal impairment is more likely).

    Pregnancy and lactation:

    Action category for the fetus by FDA - D.

    Cytarabine is contraindicated in pregnancy. If necessary, use during lactation should stop breastfeeding.

    Women of childbearing age should use reliable methods of contraception during the treatment with cytarabine.

    In experimental studies, teratogenic and embryotoxic effects of cytarabine have been established.

    Dosing and Administration:

    Intravenous (drip or slow jet), subcutaneously, intramuscularly, intrathecally (intralumably). The dosage regimen is set individually; are also used in combination with other antitumor drugs in various schemes.

    The daily dose is 100 mg / m2, the course dose for all routes of administration is 500-1000 mg. Patients with advanced age or with reduced reserves of hematopoies are prescribed in a dose of 50-70 mg / m2.

    Intravenous (drip) 100 mg / m2 per day in the form of two infusions for 3 hours with an interval of 10 hours or continuously 24 hours for 4-7 days (the maximum single dose is 3 g / m2).

    Subcutaneously at 20 mg / m2 2-3 times a day for 3-10 days (no more). Intrathecally 20 mg / m2 every 3 days for 2 weeks. Conduct 4-7 courses with an interval of 10-14 days.

    Side effects:

    From the side hematopoiesis system: thrombocytopenia, anemia, and leukopenia.

    From the side digestive system: nausea, vomiting, stomatitis, anorexia; rarely - a violation of liver function, esophagitis, diarrhea, gastrointestinal bleeding.

    From the side CNS and peripheral nervous system: paresthesia, unusual fatigue, confusion, memory loss, convulsions, tremors, dysarthria.

    From the side respiratory system: pulmonary edema, diffuse interstitial pneumonitis.

    From the side reproductive system: amenorrhea, azoospermia.

    Other: cytarabine syndrome, including pain in the bones or muscles, pain in the chest, fever, general weakness, fever, skin rash (occurs 6-12 hours after injection); conjunctivitis.

    Overdose:

    Symptoms: treatment with high doses is accompanied by a pronounced toxic effect with possible fatal outcome,including reversible toxic effects on the cornea and hemorrhagic conjunctivitis, impaired central nervous system function (confusion, fatigue, loss of memory, seizures), impaired function of the cerebellum (difficulty in conversation while standing or walking; tremor), ulceration in the gastrointestinal tract, peritonitis (including cystic pneumatosis bowel, leading to peritonitis), septicemia due to attachment of secondary infections on the background leukopenia, pulmonary edema, liver damage with hyperbilirubinemia, bowel necrosis, necrotizing colitis, skin rash, resulting conductive to desquamation, cardiomyopathy, respiratory distress syndrome, progressing to pulmonary edema and cardiomegaly, as well as peripheral sensory and motor neuropathy.

    12-fold intravenous infusion (within 1 hr) cytarabine in a dosage of 4.5 g / m2 per 12 hours causes irreversible changes in the CNS and death.

    Treatment: symptomatic, there is no specific antidote.

    Interaction:

    With the simultaneous use of cytarabine with other drugs that cause myelodepression, additive inhibition of bone marrow function is possible; with uricosuric,anti-gouty agents - may increase the risk of developing nephropathy; with immunosuppressants - it is possible to increase the risk of infection.

    When cytarabine is used after previous therapy with asparaginase, acute pancreatitis may develop.

    With simultaneous application with daunorubicin, there may be a violation of liver function; with methotrexate - mutual enhancement of cytotoxic action; with flucytosine - it is possible to reduce the antifungal effect of flucytosine; with cyclophosphamide - an increased likelihood of developing severe cardiomyopathy.

    It inhibits the absorption of digoxin in the digestive tract.

    Increased risk of infection with simultaneous use with other immunosuppressants (azathioprine, chlorambucil, cyclophosphamide, ciclosporin, mercaptopurine, glucocorticoids).

    Reduces the antifungal efficacy of allopurinol, colchicine and sulfinpyrazone.

    Drugs that cause myelosuppression, increase cytarabine-induced leukopenia and / or thrombocytopenia.

    With the introduction of live viral vaccines, it is possible to intensify the replication of the vaccine virus and to increase the side effects or decrease the production of antibodies in the patient's body in response tointroduction of the vaccine, inactivated vaccines - decrease in the production of antiviral antibodies.

    Pharmaceutically incompatible with heparin, insulin, fluorouracil, oxacillin, penicillin, methylprednisolone.

    Special instructions:

    The use of cytarabine should be performed by specially trained medical personnel in compliance with established precautions when preparing and diluting injection solutions (in a sterile box using disposable surgical gloves and masks) and destroying needles, syringes, vials, ampoules and the remainder of the unused preparation.

    The use of cytarabine should be carried out under strict control of the number of leukocytes (daily or every other day), the hematopoietic function of the bone marrow (before and after each course of therapy), liver function (at least once a week), the excretory function of the kidneys (before and after the end of the course therapy). With a decrease in the number of leukocytes below 1x109/ l or platelet count below 50x109/ l cancellation of cytarabine before the restoration of laboratory blood counts, then appoint in a lower dose.

    After 24 hours after administration, the number of leukocytes decreases,on the 7-9th day reaches the minimum values, then briefly rises to the 12th day, after which it again decreases more significantly with a minimum on the 15-24th day. In the next 10 days, the number of leukocytes increases rapidly to the baseline level. The number of platelets is significantly reduced on the 5th day after the administration of cytarabine, the lowest level is reached on the 12-15th day, reaching the baseline within the next 10 days.

    The introduction of glucocorticosteroids can prevent or reduce manifestations of cytarabine syndrome.

    During the treatment period, especially in the presence of a large number of blast cells or with a large mass of the tumor (lymphoma), it is necessary to carry out mandatory medicamentous prophylaxis of hyperuricemia and ensure the intake of allopurinol and a sufficient amount of liquid.

    In experimental studies, a mutagenic effect of cytarabine has been established.

    Special precautions (refusal of intramuscular injections, urinalysis, feces and secretions of occult blood, refusal to take acetylsalicylic acid, possible transfusion of platelets, etc.) must be observed in case of thrombocytopenia; when leukopenia - carefully monitor the development of infections.In patients with neutropenia with increasing body temperature, the use of antibiotics must begin empirically.

    In elderly patients, a dose reduction may be required (age-related renal impairment is more likely).

    Dental interventions should be completed as far as possible before the start of therapy or postponed until normalization of the blood picture (possibly increased risk of microbial infections, slowing healing, bleeding gums). During treatment, use caution when using toothbrushes, threads or toothpicks.

    Be careful with combination therapy; It is necessary to take each drug at the appointed time.

    To prevent hyperuricemia during treatment, it is important to consume enough fluids and then increase diuresis to ensure the excretion of uric acid, in some cases, the appointment of allopurinol.

    During the period of treatment, vaccination with viral vaccines is not recommended, avoid contact with people who have received a polio vaccine with sick bacterial infections.Use live viral vaccines in patients with leukemia in the remission phase should not be at least 3 months after the last course of chemotherapy. Immunization with oral polio vaccine for people in close contact with such a patient, especially family members, should be postponed.

    Appearance of signs of oppression of bone marrow function, unusual bleeding or hemorrhages, black tarry stools, blood in urine or feces or spot red spots on the skin requires immediate consultation of a doctor.

    Take care to avoid accidental cuts with sharp objects (safety razor, scissors), avoid contact sports or other situations in which there may be a bleeding or trauma.

    For the preparation of drugs for use in newborns, it is not recommended to use solvents containing benzyl alcohol. The use of solvents containing benzyl alcohol should also be avoided when preparing solutions for high-dose and intrathecal administration.

    During the period of treatment, the use of contraceptives is recommended.

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