Clinical and pharmacological group: & nbsp

Antineoplastic agents - inhibitors of protein kinases

Included in the formulation
  • Dasatinib-native
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    NATIVA, LLC     Russia
  • Spiceel®
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  • Spiceel®
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  • Spiceel®
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  • Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

    VED

    АТХ:

    L.01.X.E.06   Dasatinib

    Pharmacodynamics:

    The drug is an inhibitor of tyrosine kinases BCR-ABL and tyrosine kinases of the family SRC, as well as many other oncogenic kinases, the PDGFβ receptor and the kinase of the ephrine (EPH) receptor. By inhibiting these proteins, the growth of the cellular lines of acute lymphoblastic leukemia, chronic myeloid leukemia, occurs.

    Pharmacokinetics:

    After intake, absorption is rapid. Maximum concentration dasatinib is achieved after 0.5-3 hours. The connection with the plasma proteins of the drug is 96%, the connection with the proteins of its metabolite is 93%. Metabolised in the liver, the enzymes 3A4 cytochrome P450, uridine diphosphate glucuronosyltransferase and flavin-containing monooxygenase 3 participate in this process. Excretion mainly by the gastrointestinal tract (85%, 19% unchanged), 4% is excreted by the kidneys.

    Indications:

    Acute lymphoblastic leukemia with a positive Philadelphia chromosome; chronic myelogenous leukemia in chronic phase or in the acceleration phase, lymphoid or myeloid blast crisis.

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

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

    Contraindications:

    Pregnancy, lactation, age under 18, hypersensitivity.

    Carefully:

    Chronic liver disease, chronic kidney disease, with the joint administration of anticoagulants, drugs that affect the functional state of platelets, with an extended interval QT, hereditary lactose intolerance, lactase deficiency or impaired absorption of glucose and galactose, simultaneous application of CYP3A4 isoenzyme with substrates, simultaneous application with inhibitors or inductors of the CYP3A4 isoenzyme with a narrow therapeutic range.

    Pregnancy and lactation:

    Category FDA - D. Contraindicated in pregnancy and lactation (breastfeeding).

    Patients during treatment and at least 3 months after it is necessary to use reliable methods of contraception. For the duration of treatment with the drug, breast-feeding should be discontinued.

    Dosing and Administration:

    Orally, the first dose of 100 mg once a day, then the dose is adjusted depending on the chosen therapy, clinical parameters, individual characteristics of the patient.Tablets should be taken internally; regardless of food intake.

    Side effects:

    From the central nervous system: fainting, drowsiness, depression, neuropathy, amnesia, tremors, convulsions, reversible rear leukoencephalopathy syndrome, disturbances of cerebral circulation.

    From the hematopoiesis: anemia, hypocoagulation, thrombocytopenia, neutropenia, erythroblastopenia.

    From the skin: xeroderma, urticaria, acne, alopecia, dermatitis, pigmentation disorders, photosensitivity, bullous dermatitis, plantar-palmar syndrome eritrodizestezii, nail changes.

    From the gastrointestinal tract: vomiting, nausea, diarrhea, inflammation of the mucous membranes in the mouth, ulceration of the upper gastrointestinal tract, pancreatitis, bowel obstruction, hepatitis, cholestasis, cholecystitis, gastritis, colitis, anal fissures, dysphagia, enterocolitis, violation of appetite.

    From the respiratory system: shortness of breath, bronchospasm, pulmonary infiltrates, bronchial asthma, pulmonary edema, reticular asphyxia, cough, pleural effusion.

    On the part of the reproductive system: gynecomastia, decreased libido, menstrual cycle disorders.

    From the sense organs: dry eyes, vertigo, conjunctivitis, noise in the ears, distortion of taste.

    From the cardiovascular system: angina pectoris, tachycardia, myocardial infarction, cardiomegaly, increase / decrease in blood pressure, hot flashes, ventricular tachycardia, pericarditis, acute coronary syndrome, lengthening of the interval QT on the ECG.

    From the musculoskeletal system: muscle weakness, tendonitis, myositis, rhabdomyolysis.

    Metabolic disorders: hyperuricemia, hypoalbuminemia.

    Other: sepsis, herpetic infection, enterocolitis, hypersensitivity, fluid retention.

    Overdose:

    Clinical studies of an overdose have not been conducted, the treatment is symptomatic.

    Interaction:

    Potentiation of drug action when combined with inhibitors CYP3A4 (ketoconazole, itraconazole, erythromycin, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin), respectively, a decrease in plasma dasatinib plasma concentration with simultaneous reception with inducers CYP3A4 (dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital).

    Antacids, preparations of St. John's wort perfume reduce the concentration of the drug in the blood.

    Suppression of HCl secretion by H blockers2-histamine receptors (famotidine) and proton pump inhibitors (omeprazole) reduces the concentration of dasatinib.

    Special instructions:

    During the treatment, once a week, a clinical blood test is necessary, since many side effects from the circulatory system are possible.

    If fluid retention occurs, a course of diuretics is prescribed in parallel with the drug.

    Treatment can lead to severe thrombocytopenia, anemia and neutropenia, more often in patients with a far-advanced phase of chronic myelogenous leukemia or acute lymphoblastic leukemia with a positive Philadelphia chromosome. Oppression of the bone marrow is reversible and occurs with the temporary cancellation or reduction of the dose of the drug.

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