Azacitidine (Azacitidinum)

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

Antimetabolites

Included in the formulation
  • Vaidaz
    lyophilizate PC 
    Selden International Sarl     Switzerland
    • АТХ:

    L.01.B.C   Analogs of pyrimidine

    L.01.B.C.07   Azacitidine

    Pharmacodynamics:

    The therapeutic effect of azacitidine is in the hypomethylation of DNA and direct cytotoxic effects on pathological hemopoietic cells of the bone marrow.

    Hypomethylation helps restore the functioning of genes critical for differentiation and proliferation.

    Due to the cytotoxic effect, the death of cells prone to rapid division, including tumor cells, occurs. In this case, non-proliferating cells do not have sensitivity to azacitidine.

    The concentration of azacitidine necessary for maximum inhibition of DNA methylation does not, however, suppress the synthesis of DNA.

    Pharmacokinetics:

    After subcutaneous administration, the absorption of the substance in blood plasma is achieved after 30 minutes (750 ± 403 ng / ml). Bioavailability of azacitidine with subcutaneous administration in comparison with intravenous infusion is 89%.

    Azacitidine and its metabolites are excreted mainly by the kidneys.

    Indications:

    - refractory anemia;

    - refractory anemia with ringed sideroblasts (accompanied by neutropenia, thrombocytopenia and requiring blood transfusion);

    - refractory anemia with excess blasts;

    - Refractory anemia with excess blasts at the stage of transformation;

    - chronic myelomonocytic leukemia.

    ICD-10

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

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

    II.D37-D48.D46   Myelodysplastic syndromes

    Contraindications:

    Progressive malignant tumors of the liver; individual intolerance.

    Carefully:

    Azacitidine and its metabolites are excreted by the kidneys, which increases the risk of toxic side effects in patients with kidney disease.

    Elderly patients are dosed carefully under control kidney function.

    Pregnancy and lactation:

    Contraindicated in pregnancy. Men during the course of treatment with azacitidine should refrain from conception.

    Dosing and Administration:

    The drug is administered subcutaneously or intravenously.

    The first cycle of therapy starts with an initial dose of 75 mg / m2 n / to or in / in, for 7 days daily. In order to prevent nausea and vomiting, premedication.

    Further courses of therapy are conducted every 4 weeks with a possible increase in the dose to 100 mg / m2 in the absence of therapeutic effect after the first 2 cycles of therapy (in the absence of side effects, except for nausea and vomiting).

    The course of treatment is 4-6 cycles.Treatment can be continued as long as there is a therapeutic response.

    Conducting repeated courses of treatment requires control of the absolute number of neutrophils and platelets and toxic reactions for correcting the dose of the drug.

    With a decrease in sodium bicarbonate to <20 meq / l, a 50% reduction in the dose of azacitidine is necessary.

    With an increase in urea nitrogen or serum creatinine, it is also necessary to reduce the dose of azacitidine by 50% and keep at this level until the recovery of the indices.

    Side effects:

    Blood: anemia, leukopenia, neutropenia, thrombocytopenia, agranulocytosis, pancytopenia, splenomegaly.

    The cardiovascular system: cardiac arrest, arterial hypotension, atrial fibrillation, cardiomyopathy, heart failure, orthostatic hypotension.

    Gastrointestinal tract: nausea, vomiting, diarrhea or constipation, dyspepsia, hemorrhages and bleeding in the oral cavity, stomach and intestines, melena, diverticulitis, stomatitis, peri-rectal abscess, cholecystitis.

    Infections: nasopharyngitis, pneumonia, streptococcal pharyngitis, urinary tract infection, lower extremity abscesses, bacterial infection, cellulitis, blastomycosis,sepsis and septic shock, staphylococcal bacteremia, staphylococcal infection, toxoplasmosis.

    Nervous system: lethargy, dizziness and headache, cerebral hemorrhage, anxiety, insomnia, lethargy, convulsions, intracranial hemorrhages.

    Body of vision: hemorrhage in the eye.

    Exchange processes: weight loss, hypokalemia, dehydration.

    Musculoskeletal system: pain in the bones, muscles and joints, muscle weakness, pain in the neck.

    Urinary system: hematuria, back pain, kidney failure.

    Respiratory system: shortness of breath, pulmonary infiltration, pharyngolaryngeal pain, hemoptysis, pneumonitis, respiratory distress.

    Dermatological reactions: dry skin, ecchymosis, erythema, petechiae, bruises, rash, itching, gangrenous pyoderma, skin induration.

    Allergic reactions: urticaria, anaphylactic shock.

    Others: pain in the chest and fever.

    Overdose:No data.
    Interaction:

    The drug interaction of azacitidine has not been studied.

    Special instructions:

    Before the appointment of treatment, it is necessary to conduct blood tests and assess the condition of the liver and kidneys.A repeated examination is carried out regularly to monitor the condition of the organism and correct the dose of the drug substance.

    In patients with metastases, progression of hepatic coma and death was rarely observed (especially in patients with an initial albumin content of less than 30 g / l). Azacitidine contraindicated in patients with severe malignant liver tumors.

    At present, the safety and efficacy of azacitidine have not been established in patients with myelodysplastic syndrome and with impaired liver function.

    With the use of azacitidine IV in combination with other chemotherapeutic agents, in rare cases, abnormal changes in the kidneys (elevated serum creatinine, renal failure and death) were observed.

    In some patients who used concomitantly azacitidine and etoposide, acidosis of the renal tubules was observed (a sharp decrease in the serum bicarbonate level - less than 20 meq / l, alkalinization of urine and hypokalemia - less <3 meq / L). With an inexplicable decrease in serum bicarbonate to less than 20 meq / l, it is recommended that the dose be reduced or not changed (not increased later).

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