Dasatinib-native (Dasatinib-nativ)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceDasatinibDasatinib
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    • Dosage form: & nbspfilm-coated tablets
    Composition:

    Composition per 1 tablet:

    Ingredient name

    Amount, mg

    20 mg

    50 mg

    70 mg

    80 mg

    100 mg

    140 mg

    Active substance:

    Dasatinib

    20,0

    50,0

    70,0

    80,0

    100,0

    140,0

    Excipients:

    Lactose Monohydrate

    27,0

    67,5

    94,5

    108,0

    135,0

    189,0

    Cellulose

    microcrystalline

    27,0

    67,5

    94,5

    108,0

    135,0

    189,0

    Giprolase

    2,4

    6,0

    8,4

    9,6

    12,0

    16,8

    Croscarmellose sodium

    3,2

    8,0

    11,2

    12,8

    16,0

    22,4

    Magnesium stearate

    0,4

    1,0

    1,4

    1,6

    2,0

    2,8

    Film Sheath:

    polyvinyl alcohol - 40,00 %, macrogol - 20.20 %, talc - 14.80 %, titanium dioxide - 11,98 %, dye quinoline yellow (E104), aluminum varnish - 11.69 %, dye sunset yellow (E110), aluminum varnish - 0.73 %, dye iron oxide yellow - 0.58 %, dye indigokarmin (E132), aluminum varnish - 0.02 %

    4,0

    -

    11,0

    -

    16,0

    -

    polyvinyl alcohol - 40,00 %, macrogol - 20,20 %, talc - 14.80 %, dye sunset yellow (E110), aluminum varnish - 13.91 %, titanium dioxide - 10.14%, iron oxide, yellow oxide - 0.91%, dye indigo carmine (E132), aluminum varnish - 0.04%

    -

    8,0

    -

    13,0

    -

    23,0
    Description:

    Dosage of 20 mg. Round, biconvex tablets, covered with a film coating of yellow color. On the cross section, the nucleus is white or almost white in color.

    Dosage of 50 mg. Oval, biconvex tablets, covered with a film shell of orange color. On the cross section, the nucleus is white or almost white in color.

    Dosage of 70 mg. Round, biconvex tablets, covered with a film coating of yellow color. On the cross section, the nucleus is white or almost white in color.

    Dosage of 80 mg. Round, biconvex tablets, covered with a film shell of orange color. On the cross section, the nucleus is white or almost white in color.

    Dosage of 100 mg. Round, biconvex tablets, covered with a film coating of yellow color. On the cross section, the nucleus is white or almost white in color.

    Dosage of 140 mg. Round, biconvex tablets, covered with a film shell of orange color. On the cross section, the nucleus is white or almost white in color.

    Pharmacotherapeutic group:Antitumor agent - protein tyrosine kinase inhibitor
    ATX: & nbsp

    L.01.X.E.06   Dasatinib

    Pharmacodynamics:

    Dasatinib inhibits tyrosine kinase BCR-ABL and family tyrosine kinase SRC, as well as many other oncogenic kinases, including c-KIT, the kinase of the ephrine (EPH) receptor and PDGFβ-receptor. Dasatinib binds to the active and inactive forms of the enzyme BCR-ABL and at subnanomolar concentrations (0.6-0.8 nmol / ml) inhibits it.

    Mechanism of action

    In conditions in vitro dasatinib shows activity on cellular models of leukemia, both in relation to sensitive and resistant to imatinib cells. Dasatinib overcomes the resistance to imatinib associated with overexpression BCR-ABL, domain mutations BCR-ABL kinase activation of alternative mechanisms inducing family kinases SRC (LYN, NSC), as well as overexpression of the multiple drug resistance gene. When investigating domain mutations BCR-ABL in patients with newly diagnosed chronic myeloid leukemia in the chronic phase who stopped taking dasatinib, mutations of T3151, F317I/L and V299L. Based on experiments in vitro dasatinib does not appear to be active against the T315 mutationI.

    Pharmacokinetics:

    Suction

    Absorption is fast. The maximum concentration of dasatinib is observed after 0.5-3 hours after oral administration.

    Area under the curve "concentration-time" (AUC) and excretion are dose-dependent in the dose range from 25 to 120 mg twice a day. When taking a single dose of 100 mg of dasatinib 30 minutes after a meal with a high fat content, an increase in the mean AUC by 14%, after eating low-fat food - by 21%.Eating does not have a significant effect on absorption.

    Distribution

    The apparent volume of distribution of dasatinib in patients is 2505 liters, which indicates its significant distribution in the extravascular space. The binding of dasatinib, in concentrations used in clinical practice, with plasma proteins is 96%.

    Metabolism

    Isozyme CYP3A4 is the main enzyme responsible for the metabolism of dasatinib. After oral administration of 100 mg [14C] -dazatinib by healthy volunteers, 29% of the radioactivity in the blood plasma is accounted for by the unchanged dasatinib. Judging by the concentration in the blood plasma and activity in vitro it can be assumed that metabolites do not play a big role in the pharmacological action of dasatinib.

    Excretion

    The average total terminal half-life (T1 / 2) of dasatinib in patients is 5-6 hours. Dasatinib is mainly derived from the intestines in the form of metabolites. After a single oral intake of [14C] -dazatinib 4% and 85% of radioactivity are excreted by the kidneys and intestines respectively for 10 days. The proportion of unchanged dasatinib is 0.1% and 19% of the dose excreted by the kidneys and intestines, respectively, the rest of the dose is metabolites.

    Pharmacokinetics the separate patient groups

    Patients with hepatic impairment

    The pharmacokinetics of dasatinib were studied in 8 patients with moderate hepatic impairment after a single dose of 50 mg and in 5 patients with severe hepatic dysfunction after a single dose of 20 mg dose of dasatinib compared with pharmacokinetics in healthy volunteers after dasatinib administration in a dose 70 mg. The values ​​of the maximum concentration (CmOh) and AUC for dasatinib were lower by 47% and 8%, respectively, in patients with impaired liver function of the average degree compared to the values ​​obtained in healthy volunteers. In patients with impaired hepatic function, a severe decrease in CmOh and AUC for dasatinib reached 43% and 28%, respectively.

    Patients with impaired renal function

    In patients with impaired renal function, the pharmacokinetics of dasatinib does not change.
    Indications:

    - The first detected chronic myelogenous leukemia in the chronic phase.

    - Chronic myelogenous leukemia in the chronic phase, the phase of acceleration or phase of the myeloid or lymphoid blast crisis with resistance or intolerance to previous therapy, including imatinib.

    - Acute lymphoblastic leukemia with a positive Philadelphia chromosome (Ph+ ALL) with resistance or intolerance to previous therapy.

    Contraindications:

    - Hypersensitivity to dasatinib or other components of the drug.

    - Pregnancy and the period of breastfeeding.

    - Age to 18 years (effectiveness and safety not established).

    Carefully:

    Dasatinib-native should be used with caution in patients with the following diseases: liver failure, lengthening the interval QT on the ECG or the risk of its elongation (hypokalemia, hypomagnesemia, congenital syndrome of elongated QT interval, therapy with antiarrhythmic and other drugs capable of lengthening QT interval, previous therapy with high doses of anthracyclines), hereditary lactose intolerance, lactase deficiency or malabsorption of glucose and galactose (formulation contains lactose), and at the same time taking anticoagulants and drugs affecting platelet function isoenzyme substrates CYP3A4 with a narrow therapeutic range.

    Pregnancy and lactation:

    Patients during treatment and for at least 3 months after completion of the need to use reliable methods of contraception. If pregnancy occurred during drug treatment Dasatinib-native, and if it became known that the drug was used during pregnancy, the patient should immediately be informed of the possible risk to the fetus. There is evidence that the use of dasatinib during pregnancy can lead to spontaneous abortion, as well as cause fetal and neonatal abnormalities.

    It is not known whether the dasatinib in breast milk. At the time of drug treatment Dasatinib-native breast-feeding should be discontinued.

    Dosing and Administration:

    Tablets of the drug Dasatinib-native should be taken internally, regardless of food intake.

    Recommended starting doses

    - 100 mg once a day (morning or evening) in the chronic phase of chronic myelogenous leukemia;

    - 140 mg once a day (morning or evening) in the remaining cases.

    A dose change is possible in view of the clinical response and tolerability of the drug by the patient.

    Increase in dose

    In the absence of a hematologic or cytogenetic response at the recommended initial dose, an increase in the dose of the drug Dasatinib-native before:

    - 140 mg once a day for the chronic phase of chronic myelogenous leukemia;

    - 180 mg once daily for advanced phases of chronic myelogenous leukemia (phase of acceleration or blast crisis) or acute lymphoblastic leukemia with a positive Philadelphia chromosome (Ph + ALL).

    Acceptance of the drug is discontinued if there are signs of progression of the disease or when the patient is intolerant of the drug.

    Correction of dose due to development of adverse reactions

    Myelosuppression

    When myelosuppression should reduce the dose, interrupt therapy or cancel it. If necessary, transfusions of platelet or erythrocyte mass should be performed. With stable myelosuppression, it is possible to use hematopoietic growth factors.

    Neutropenia and thrombocytopenia

    Chronic phase of chronic myelogenous leukemia (initial dose of 100 mg once a day) With an absolute number of neutrophils <0.5 x 109/ l or the number of platelets <50 x 109/ l it is necessary:

    1. To take a break in the treatment with the drug Dasatinib-native until the absolute number of neutrophils is reached ≥ 1.0 x 109/ l and the number of platelets ≥ 50 x 109/ l.

    2. Resume the therapy in the previous dose.

    3. When the number of platelets is less than 25 x 109/ l or an absolute number of neutrophils less than 0.5 x 109/ l, observed for more than 7 days, it is necessary to take a break in treatment and after reaching the initial parameters of therapy to resume at a reduced dose of 80 mg once a day (second episode). For patients with newly diagnosed chronic myelogenous leukemia in the chronic phase, the third episode of thrombocytopenia or neutropenia reduces the dose to 50 mg once a day. At the onset of the third episode of thrombocytopenia and neutropenia in patients with other phases of myeloid leukemia and the presence of resistance to previous therapy with other drugs (including imatinib) or her intolerance stop the drug treatment Dasatinib-native.

    Chronic myelogenous leukemia (in the phase of acceleration or blast crisis) and acute lymphoblastic leukemia with a positive Philadelphia chromosome (Ph + ALL) (initial dose of 140 mg once a day)

    With an absolute number of neutrophils <0.5 x 109/ l or the number of platelets <10 x 109/ l it is necessary:

    1. Determine whether leukemia is caused by cytopenia (aspiration or bone marrow biopsy).

    2. If cytopenia is not associated with leukemia, treatment should be discontinued until an absolute neutrophil count of ≥ 1.0 x 109/ l and the number of platelets ≥ 20 x 109/ l and resume therapy at the previous dose.

    3. In the case of recurrence of cytopenia, the nature of cytopenia should be re-verified and therapy resumed at a reduced dose of 100 mg once a day (second episode) or 80 mg once a day (third episode).

    4. If the resulting cytopenia is associated with leukemia, you should consider increasing the dose to 180 mg once a day.

    In the development of severe non -hematological adverse reactions, treatment is suspended until the symptoms of an unwanted reaction disappear or the patient's condition improves. Treatment can be resumed in a reduced dose.

    Patients with impaired renal function

    The renal clearance of dasatinib and its metabolites is <4%, so dose adjustment for renal dysfunction is not required.

    Patients with hepatic impairment

    Dasatinib is metabolized mainly by the liver, so the drug should be used with caution in patients with impaired liver function of moderate to severe severity.

    Older and older patients

    Clinically significant differences in pharmacokinetics in elderly and older patients have not been identified, so dose adjustment is not required.

    Side effects:

    Have In most patients, adverse reactions are transient.Treatment with dasatinib was discontinued due to the development of unwanted reactions in 12% of patients with a newly diagnosed chronic phase of chronic myelogenous leukemia, as well as 15% of patients in the chronic phase of chronic myelogenous leukemia with resistance to imatinib or its intolerance, 16% in the phase of accelerated chronic myeloid leukemia , 15% in the phase of the myeloid blast crisis of chronic myelogenous leukemia, and also in 8% of patients with acute lymphoblastic leukemia with a positive Philadelphia chromosome. The undesirable reactions presented below are listed in accordance with the damage to organs and organ systems and frequency of occurrence. The incidence of undesirable reactions is estimated as follows: "very often" arising -> 10%; "often" -> 1 % and <10%, "infrequently" -> 0.1% and <1%, "rarely" -> 0.01% and <0.1%, "very rarely" - <0.01% "frequency is unknown" (connection with dasatinib intake is not proven).

    Infectious and parasitic diseases: very often - infections (including bacterial, viral, fungal); often - pneumonia (including bacterial, viral and fungal), upper respiratory tract infections, herpetic infections, enterocolitis, sepsis (including infrequently - with fatal outcome); frequency unknown - reactivation of hepatitis B virus.

    Violations from the blood and lymphatic system: very often - myelosuppression (including anemia, neutropenia, thrombocytopenia); often - febrile neutropenia; infrequently - lymphadenopathy, lymphopenia; rarely - erythroblastopenia.

    Immune system disorders: infrequently - Hypersensitivity reactions (including erythema nodosum).

    Disorders from the endocrine system: infrequently - hypothyroidism; rarely - hyperthyroidism, thyroiditis.

    Disorders from the metabolism and nutrition: often - disorders of appetite (including a decrease in appetite, early satiety, increased appetite), hyperuricemia; infrequently - hypoalbuminemia, tumor lysis syndrome, dehydration, hypercholesterolemia; rarely - diabetes.

    Mental disorders: often - Insomnia, depression, drowsiness; infrequently - anxiety, emotional lability, psychosis, decreased libido.

    Disorders from the nervous system: very often - headache; often - Neuropathy (including peripheral neuropathy), dizziness, dysgeusia (perversion of taste); infrequently - hemorrhages (such as intracerebral hematoma, intracerebral hemorrhage, epidural hematoma, intracranial hemorrhage, hemorrhagic stroke, subarachnoid hemorrhage, subdural hematoma, subdural hemorrhage), tremor, fainting, amnesia, imbalance; rarely - convulsions, cerebrovascular accident (stroke), transient ischemic attack, inflammation of the optic nerve, paralysis of the VII pair of cranial nerves (facial nerve), ataxia, dementia.

    Disorders from the side of the organ of vision: often - visual disorders (blurred vision, blurred vision, decreased visual acuity), dry eyes, bleeding in the sclera of the eye, conjunctival hemorrhages; infrequently - conjunctivitis, visual disturbances, photophobia, lacrimation.

    Hearing disorders and labyrinthine disturbances: often - noise in ears; infrequently - Vertigo, hearing loss.

    Heart Disease: Frequent - pericardial effusion, arrhythmia (including tachycardia), cardiac dysfunction (including ventricular dysfunction, heart failure, congestive heart failure, cardiomyopathy, congestive cardiomyopathy,diastolic dysfunction, ejection fraction reduction, ventricular failure), palpitations, increased brain natriuretic peptide activity, right ventricular dysfunction, ventricular hypokinesia; infrequently - lengthening of the interval QT ECG, angina pectoris, cardiomegaly, pericarditis, ventricular arrhythmia (including ventricular tachycardia), myocardial infarction (including fatal outcome), changes in the T wave, increased troponin activity; rarely - "pulmonary heart", myocarditis, acute coronary syndrome, cardiac arrest, lengthening of the interval PR, ischemic heart disease, pleuropericarditis; frequency unknown Atrial fibrillation / atrial flutter.

    Vascular disorders: very often - bleeding (such as nasal bleeding, gum bleeding, hematomas, petechiae, purpura); often - "hot flashes", increased blood pressure; infrequently - lowering of arterial pressure, thrombophlebitis; rarely - "marbling of the skin", deep vein thrombosis, embolism.

    Disturbances from the respiratory system, chest and mediastinal organs: very often - pleural effusion, shortness of breath; often - pulmonary infiltrates, pulmonary edema, pneumonitis, pulmonary hypertension, cough; infrequently - bronchial asthma, bronchospasm, pulmonary arterial hypertension, dysphonia; rarely - acute respiratory distress syndrome, pulmonary embolism; frequency unknown - interstitial lung diseases, pneumonia.

    Disorders from the gastrointestinal tract: Often - diarrhea, nausea, vomiting, abdominal pain; often - inflammation of the mucous membranes (including mucositis / stomatitis), gastrointestinal bleeding, dyspepsia, bloating, constipation, gastritis, soft tissue damage to the oral cavity (including dry mouth, cheilitis, vesicular rash on the lips, dry lips, ulcers on the lips, erosion mucous membrane of the oral cavity), colitis (including neutropenic colitis); infrequently - Dysphagia, ascites, anal fissures, ulceration of the upper gastrointestinal tract, pancreatitis, esophagitis, gastroesophageal reflux disease; rarely - gastrointestinal enteropathy with protein loss, intestinal obstruction, acute pancreatitis, anal fistula; frequency unknown - Gastrointestinal hemorrhage with a lethal outcome.

    Disorders from the liver and bile ducts: infrequently - Cholestasis, cholecystitis, hepatitis.

    Disturbances from the skin and subcutaneous tissues: very often - skin rash (including drug rash, erythema, erythema multiforme, papular rash, pustular rash, skin peeling, vesicular rash); often - itching, acne, alopecia, dry skin, hyperhidrosis, urticaria, dermatitis (including eczema); infrequently - skin ulcers, bullous dermatosis, pigmentation disorders, nail lesions, photosensitization, panniculitis, palmar-plantar erythrodysesthesia syndrome, changes in the hairline, neutrophilic dermatosis; rarely - leukocytoclastic vasculitis, skin fibrosis; frequency unknown - Stevens-Johnson syndrome.

    Disorders from the musculoskeletal and connective tissue: very often - musculoskeletal pain; often - Arthralgia, muscle weakness, myalgia, musculoskeletal stiffness, muscle spasms; infrequently - rhabdomyolysis, myositis, tendonitis, osteonecrosis, arthritis.

    Disorders from the nights and urinary tracts: infrequently - Renal insufficiency, frequent urination, proteinuria, hematuria; rarely - impaired renal function.

    Violations of the genitals and mammary gland: infrequently - gynecomastia, menstrual irregularities, vaginal bleeding, uterine bleeding; rarely - spontaneous abortion.

    General disorders and disorders at the injection site: very often - peripheral edema (including localized edema of subcutaneous tissue of various locations, gravitational edema), edema of the face (including edema of the tongue, edema of the lips, edema of the mouth, edema of the conjunctiva, edema in the eye and eyelids, edema of orbital tissue, periorbital edema, macular edema, puffiness face), increased fatigue, increased body temperature; often - generalized edema, asthenia, pain, chest pain, chills, decreased or increased body weight, confusion; infrequently - malaise, increased activity of creatine phosphokinase, increased activity of gamma-glutamyltranspeptidase; rarely - violation of gait.

    Laboratory and instrumental data: frequency unknown - Thrombocytopenia, anemia and neutropenia of grade 3 or 4, especially in patients with advanced phases of chronic myelogenous leukemia or acute lymphoblastic leukemia with a positive Philadelphia chromosome, hypokalemia, hypocalcemia, hypophosphatemia,an increase in the activity of hepatic transaminases (alanine aminotransferase (ALT), aspartate aminotransferase (ACT)), an increase in the concentration of bilirubin and / or creatinine in the blood plasma.

    The most frequent adverse reactions with dasatinib in patients with newly diagnosed chronic myelogenous leukemia in the chronic phase are fluid retention and diarrhea, and in patients with imatinib resistance or intolerance - fluid retention and diarrhea, headache, dyspnea, rash, fatigue, nausea, hemorrhage (such as gastrointestinal bleeding and others).

    If any of the unwanted reactions listed in the manual is aggravated or you notice any other undesirable reactions not listed in the instructions, inform the doctor about it.

    Overdose:

    The cases of dasatinib overdose were recorded in two patients who took 280 mg of dasatinib per day for 1 week, which resulted in a significant decrease in the number of thrombocytes. In case of drug overdose

    Dasatinib-native careful monitoring of patients is required to control the degree of myelosuppression; if necessary, symptomatic therapy.

    Interaction:

    Medicinal products, which can increase the concentration of dasatinib in the blood plasma

    Inhibitor inhibitors CYP3A4

    Dasatinib is a substrate of isoenzyme CYP3A4. Isoenzyme inhibitors CYP3A4 (e.g., ketoconazole, itraconazole, erythromycin, clarithromycin, ritonavir, atazanavir, indinavir, nelfinavir, saquinavir, telithromycin, grapefruit juice) can increase the concentration of dasatinib in the blood plasma, therefore, their combined use with dasatinib should be avoided. Patients who can not avoid the systemic intake of a potent inhibitor of isoenzyme CYP3A4, should be carefully monitored for the timely detection of signs of toxicity.

    Medicinal products, which can reduce the concentration of dasatinib in the blood plasma

    Inductors of isoenzyme CYP3A4

    Inductors of isoenzyme CYP3A4 can reduce the concentration of dasatinib in the blood plasma. The joint use of powerful isoenzyme inducers should be avoided CYP3A4 with dasatinib. Patients taking isoenzyme inducers CYP3A4 (e.g., dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital or preparations of St. John's wort perfumed (Hypericum perforatum)), instead of these medicines should be prescribed drugs that do not (or have a minimal degree of) ability to induce this isoenzyme.

    Antacids (medicines containing aluminum hydroxide / magnesium hydroxide)

    If antacids are needed, it is recommended that they be taken at least 2 hours before or 2 hours after dasatinib intake.

    Blockers of H2-histamine receptors and proton pump inhibitors

    Long-term suppression of gastric acid secretion with H2-histamine receptor blockers and proton pump inhibitors (eg, famotidine and omeprazole) can lead to a decrease in dasatinib concentration. The combined use of these drugs and dasatinib is not recommended. As their alternative, you can use antacids (2 hours before or 2 hours after taking dasatinib).

    Effect of dasatinib on other drugs

    Substrates of the isoenzyme CYP3A4

    Dasatinib is an isoenzyme inhibitor CYP3A4, therefore its combined use with isoenzyme substrates CYP3A4 can enhance the action of this substrate. Substrates of the isoenzyme CYP3A4 with a narrow therapeutic range, such as alfentanil, astemizole, terfenadine, cisapride, ciclosporin, fentanyl, pimozide, quinidine, sirolimus, tacrolimus and ergot alkaloids (ergotamine, dihydroergotamine) should be used with caution in patients receiving dasatinib.

    Special instructions:

    When treating the drug Dasatinib-native may occur severe (grade 3 and 4 according to the general toxicity criteria of the National Cancer Institute of the United States (NCI CTC)) thrombocytopenia, anemia and neutropenia. More often they appear in patients with advanced phases of chronic myelogenous leukemia or acute lymphoblastic leukemia with a positive Philadelphia chromosome than in patients with a chronic phase of chronic myelogenous leukemia.

    A complete clinical blood test should be performed weekly in the first 2 months of treatment with the drug Dasatinib-native, and then monthly or more often, according to clinical indications. Oppression of the bone marrow is usually reversible and occurs with the temporary cancellation or reduction of the dose of dasatinib. In patients with newly diagnosed chronic myelogenous leukemia, myelosuppressionwas less common than in patients in the chronic phase of myeloid leukemia with resistance to imatinib or its intolerance.

    When dasatinib is taken, there are reports of severe cerebral hemorrhages, including fatal ones, registered in less than 1% of patients with imatinib resistance or intolerance who received dasatinib. Severe gastrointestinal bleeding was noted in 4% of patients with resistance to imatinib or its intolerance; they usually required a temporary abolition of dasatinib and blood transfusions. Other severe bleeding was reported in 2% of patients with imatinib resistance or intolerance. Most cases of bleeding were associated with severe thrombocytopenia.

    When taking dasatinib, fluid retention may occur. Among patients with newly diagnosed chronic myeloid leukemia, severe fluid retention was observed in 3% of patients. In patients with imatinib resistance or intolerance, severe fluid retention (3 and 4) was detected in 8%, including pronounced pleural and pericardial effusion in 7% and 1% of patients, respectively.Pronounced ascites and generalized edema developed in less than 1% patients with resistance to imatinib. 1% of patients with imatinib resistance have severe pulmonary edema.

    When dyspnea, chest pain, or dry cough occurs, chest radiographs are needed. Fluid retention is usually stopped with maintenance therapy with the inclusion of diuretics or a short course of glucocorticosteroids. With pronounced pleural effusion, oxygen therapy and thoracocentesis may be required. Fluid retention often occurs in patients taking dasatinib twice a day.

    Such undesirable reactions as fluid retention, dyspnea, fast fatigue, pleural effusion, cough, bleeding in the lower gastrointestinal tract, appetite disorders, bloating, dizziness, pericardial effusion, congestive heart failure, weight loss are more common in patients over 65 years of age , therefore, careful monitoring of patients of this age group should be ensured.

    Elongation QT interval was observed in less than 1% of patients with newly diagnosed chronic myelogenous leukemia inchronic phase, who received dasatinib, while the elongation averaged 3.0 ms. Elongation QT interval in the treatment of dasatinib was observed in more than 1% of patients with resistance or intolerance to imatinib therapy. Dasatinib should be administered with caution in patients with an elongated QT interval or risk of its lengthening (hypokalemia, hypomagnesemia, congenital syndrome of elongated QT interval, therapy with antiarrhythmic and other drugs that can lengthen QT interval, prior therapy with high doses of anthracyclines). Before prescribing Dasatinib-native should correct hypokalemia and hypomagnesemia to prevent lengthening of the interval QT.

    Patients with a history of heart disease or a risk of their development among unwanted reactions are more likely than other groups of patients to have cardiovascular disorders (pericardial effusion, arrhythmia, palpitations, lengthening of the interval QT, myocardial infarction (including fatal). In view of this, in this group of patients during drug therapy Dasatinib-native it is necessary to carefully monitor the parameters of the cardiac activity in order to identify and, if necessary, correct possible adverse reactions from the cardiovascular system.

    With the development of hypocalcemia, the condition is corrected by ingestion of calcium preparations. When the activity of transaminases or bilirubin concentration increases, the dose of the drug should be reduced Dasatinib-native or stop receiving it.

    When dasatinib is used, cases of development of pulmonary arterial hypertension (PAH), confirmed with the help of right heart catheterization, are described. LAS was noted both during treatment with dasatinib, and after a year or more after its termination. Often in cases of development of PAH in the treatment of dasatinib, patients had comorbid diseases or during treatment they took concomitantly dasatinib and other medicines. Before starting treatment with the drug Dasatinib-native a patient should be examined to identify possible signs and symptoms of heart and lung diseases. If during treatment with the drug Dasatinib-native patient marked dyspnea or fatigue, you must delete most typical etiology, including pleural effusions, pulmonary edema, anemia and the presence of infiltrate in the lungs. Thus it is necessary to take into account the recommendations given in the section "Method of administration and dose" for the cases of non-hematological adverse events: the development of severe non-hematological adverse reactions suspend treatment before the disappearance of symptoms undesired reactions or to improve the patient's condition. If a different diagnosis was not made during the examination of the patient, the diagnosis of PAH should be taken into consideration. In case of confirmation of PAH in a patient, treatment with a drug Dasatinib-native it is necessary to stop without further resumption, providing subsequent monitoring of the patient's condition in accordance with standard recommendations. After the abolition of dasatinib in patients with PAH, there was an improvement in their hemodynamic and clinical parameters.

    When receiving dasatinib noted individual cases of severe adverse reactions affecting the skin and mucous membranes, including Stevens-Johnson syndrome and erythema multiforme.In case of occurrence of such undesirable reactions in the form of dasatinib intake, drug treatment Dasatinib-native it is necessary to stop.

    Inhibitors of tyrosine kinase BCR-ABL associated with the reactivation of the hepatitis B virus (HBV), isolated cases are described for dasatinib. In some cases, the reactivation of HBV when using other tyrosine kinase inhibitors BCR-ABL led to the development of acute hepatic insufficiency or fulminant hepatitis, and subsequently to liver transplant or fatal outcome. Before starting therapy with the drug Dasatinib-native screening for BDB. For patients, having positive serological tests, it is recommended to consult a specialist who has experience of HBV treatment. In patients with HBV carriers who need treatment with tyrosine kinase inhibitors BCR-ABL, it is necessary to monitor the clinical and laboratory parameters of HBV activation during therapy and several months after its termination. For patients with reactivated HBV on the background of the drug Dasatinib-native an immediate consultation with an HBV treatment specialist is indicated.

    Lactose content

    A drug Dasatinib-native contains lactose: in a daily dose of 100 mg - 135 mg of lactose and in a daily dose of 140 mg - 189 mg of lactose.

    Effect on the ability to drive transp. cf. and fur:

    Studies on the effect of dasatinib on the ability to drive vehicles and mechanisms were not conducted. If the patient observes treatment-related drugs Dasatinib-native symptoms such as dizziness and visual impairment that affect its ability to concentrate and respond quickly, it is recommended to refrain from controlling vehicles and mechanisms, as well as from engaging in other potentially dangerous activities requiring increased concentration and speed of psychomotor reactions.

    Form release / dosage:Film-coated tablets, 20 mg, 50 mg, 70 mg, 80 mg, 100 mg, 140 mg.
    Packaging:

    Dosage of 20 mg, 50 mg, 70 mg. For 60 tablets in bottles of polyethylene, sealed with lids made of polyethylene with a desiccant, with a control ring of the first opening or without it.

    Dosage of 80 mg, 100 mg, 140 mg. For 30 tablets in bottles of polyethylene, sealed with lids made of polyethylene with a desiccant, with a control ring of the first opening or without it.

    The labels are glued on the vials.

    On 1 bottle together with the instruction on application place in a pack a cardboard.
    Storage conditions:

    In the dark place at a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    2 years.

    Do not use after the expiration date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-004202
    Date of registration:20.03.2017
    Expiration Date:20.03.2022
    The owner of the registration certificate:NATIVA, LLC NATIVA, LLC Russia
    Manufacturer: & nbsp
    Information update date: & nbsp17.04.2017
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