Name: Dasatinib (Dasakast) 50 mg 60 tab. buy
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Dasatinib (Dasakast) 50 mg 60 tab.

Product Details

Dasatinib (Dasakast) 50 mg 60 tab.

Dasakast 70 mg tablet is used in the treatment of blood cancer (chronic myeloid leukemia). It is used in patients whose disease cannot be treated with other leukemia medications. You can buy Dasatinib (Dasakast) 70 mg 60 tab. the drug from India by placing an order in our company.

Description

The dosage is 20 mg. Round, biconvex tablets coated with a yellow film coating. In the cross section, the core is white or almost white in color.

The dosage is 50 mg. Oval, biconvex tablets, coated with an orange film coating. In the cross section, the core is white or almost white in color.

The dosage is 70 mg. Round, biconvex tablets coated with a yellow film coating. In the cross section, the core is white or almost white in color.

The dosage is 80 mg. Round, biconvex tablets coated with an orange film coating. In the cross section, the core is white or almost white in color.

The dosage is 100 mg. Round, biconvex tablets coated with a yellow film coating. In the cross section, the core is white or almost white in color.

The dosage is 140 mg. Round, biconvex tablets coated with an orange film coating. In the cross section, the core is white or almost white in color.

Pharmacotherapeutic group

Antitumor agent - protein tyrosine kinase inhibitor

ATX Code

L01XE06

Pharmacodynamics:

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

Mechanism of action

Under invitro conditions, dasatinib is active on cell models of leukemia, both in relation to sensitive and imatinib-resistant cells. Dasatinib overcomes resistance to imatinib associated with overexpression of BCR-ABL, mutations of the BCR-ABL kinase domain, activation of alternative mechanisms inducing kinases of the SRC family (LYN, NSC), as well as overexpression of the multidrug resistance gene. When studying mutations of the BCR-ABL domain in patients with newly diagnosed chronic myeloid leukemia in the chronic phase who stopped taking dasatinib, mutations T3151, F317I/L and V299L were detected. Based on the invitro experiments, dasatinib does not appear to be active against the T315I mutation.

Pharmacokinetics:

Suction

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

The area under the concentration-time curve (AUC) and excretion are dose-dependent in the dose range from 25 to 120 mg 2 times a day. When taking a single dose of 100 mg of dasatinib 30 minutes after eating a high-fat meal, there is an increase in the average AUC value by 14%, after eating a low-fat meal - 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, to plasma proteins is 96%.

Metabolism

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

Withdrawal

The average total terminal half-life (T1/2) of dasatinib in patients is 5-6 hours. Dasatinib is mainly excreted by the intestine mainly in the form of metabolites. After a single oral administration of [14C]-dasatinib, 4% and 85% of radioactivity are excreted by the kidneys and intestines, respectively, within 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 represented by metabolites.

Pharmacokinetics in selected groups of patients

Patients with impaired liver function

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 impairment after a single dose of dasatinib at a dose of 20 mg compared with the pharmacokinetics in healthy volunteers after taking dasatinib at a dose of 70 mg. The maximum concentration (Cmax) and AUC values for dasatinib were 47% and 8% lower, respectively, in patients with moderate hepatic impairment compared with the values obtained in healthy volunteers. In patients with severe hepatic impairment, the decrease in Cmax and AUC values 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:

- Chronic myeloid leukemia in the chronic phase has been identified for the first time.

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

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

Contraindications:

- Hypersensitivity to dasatinib or other components of the drug.

- Pregnancy and breastfeeding.

- Age under 18 years (efficacy and safety have not been established).

With caution:

Dasatinib-native should be used with caution in patients with the following diseases: liver failure, prolongation of the QT interval on the ECG or the risk of its prolongation (hypokalemia, hypomagnesemia, congenital syndrome of prolonged QT interval, therapy with antiarrhythmic and other drugs capable of prolonging the QT interval, previous therapy with high doses of anthracyclines), hereditary lactose intolerance, insufficiency lactase or glucose and galactose malabsorption (the drug contains lactose), and also with simultaneous administration of anticoagulants and drugs that affect platelet function, substrates of the CYP3A4 isoenzyme with a narrow therapeutic range.

Pregnancy and lactation:

Patients should use reliable methods of contraception during treatment and for at least 3 months after its completion. If pregnancy occurred during treatment with Dasatinib-native, as well as if it became known that the drug was used during pregnancy, the patient should be immediately 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 developmental abnormalities of the fetus and newborns.

It is unknown whether dasatinib penetrates into breast milk. Breast-feeding should be stopped during treatment with Dasatinib-native.

Dosage and administration:

Tablets of the drug Dasatinib-native should be taken orally as a whole, regardless of food intake.

Recommended initial doses

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

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

A dose change is possible taking into account the clinical response and tolerability of the drug by the patient.

Increasing the dose

In the absence of a hematological or cytogenetic response at the recommended initial dose, it is possible to increase the dose of Dasatinib-native to:

- 140 mg once a day in the chronic phase of chronic myeloid leukemia;

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

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

Dose adjustment due to the development of adverse reactions

Myelosuppression

In case of myelosuppression, the dose should be reduced, therapy should be interrupted or canceled. If necessary, platelet or erythrocyte mass transfusion should be performed. With stable myelosuppression, the use of hematopoietic growth factors is possible.

Neutropenia and thrombocytopenia

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

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

2. Resume therapy at the same dose.

3. If the number of platelets is less than 25 x 109 / l or the absolute number of neutrophils is 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 baseline values, therapy should be resumed at a reduced dose of 80 mg 1 time per day (second episode). For patients with newly diagnosed chronic myeloid leukemia in the chronic phase, at the onset of the third episode of thrombocytopenia or neutropenia, the dose is reduced to 50 mg 1 time per day. Upon 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 its intolerance, treatment with Dasatinib-native is discontinued.

Chronic myeloid leukemia (in the acceleration phase or blast crisis) and acute lymphoblastic leukemia with positive Philadelphia chromosome (Ph+ ALL) (initial dose 140 mg 1 time per day)

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

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

2. If cytopenia is not associated with leukemia, treatment should be interrupted until the absolute number of neutrophils ≥ 1.0 x 109 / l and platelet count ≥ 20 x 109/ l are reached and therapy should be resumed at the same dose.

3. In case of recurrence of cytopenia, the nature of cytopenia should be re-verified and therapy resumed at a reduced dose of 100 mg 1 time per day (second episode) or 80 mg 1 time per day (third episode).

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

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

Patients with impaired renal function

The renal clearance of dasatinib and its metabolites is < 4%, therefore, dose adjustment in case of impaired renal function is not required.

Patients with impaired liver function

Dasatinib is mainly metabolized by the liver, so the drug should be used with caution in patients with moderate to severe hepatic impairment.

Elderly and older patients

There were no clinically significant differences in pharmacokinetics in elderly and older patients, so dose adjustment is not required.

Side effects:

Most patients have transient adverse reactions. Treatment with dasatinib was discontinued due to the development of adverse reactions in 12% of patients with newly diagnosed chronic phase of chronic myeloid leukemia, as well as in 15% of patients in the chronic phase of chronic myeloid leukemia with resistance to or intolerance to imatinib, in 16% - in the phase of acceleration of chronic myeloid leukemia, in 15% - in the phase of myeloid blast crisis chronic myeloid leukemia, as well as in 8% of patients with acute lymphoblastic leukemia with a positive Philadelphia chromosome. The adverse reactions presented below are listed according to the lesion of organs and organ systems and the frequency of occurrence. The frequency of adverse reactions is estimated as follows: occurring "very often" - > 10%; "often" - > 1% and < 10%, "infrequently" - > 0.1% and < 1%, "rarely" - > 0.01% and < 0.1%, "very rarely" - < 0.01%, including individual reports, "frequency unknown" (association with dasatinib has not been proven).

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

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

Disorders of the immune system: infrequently - hypersensitivity reactions (including erythema nodosum).

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

Metabolic and nutritional disorders: often - appetite disorders (including decreased appetite, early satiety, increased appetite), hyperuricemia; infrequently - hypoalbuminemia, tumor lysis syndrome, dehydration, hypercholesterolemia; rarely - diabetes mellitus.

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

Disorders of 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 - seizures, impaired cerebral circulation (stroke), transient ischemic attack, inflammation of the optic nerve, paralysis of the VII pair of cranial nerves (facial nerve), ataxia, dementia.

Visual disturbances: often - visual disorders (blurriness, blurriness, decreased visual acuity), dry eyes, hemorrhages in the sclera of the eye, conjunctival hemorrhages; infrequently - conjunctivitis, visual disturbances, photophobia, lacrimation.

Hearing disorders and labyrinthine disorders: often - tinnitus; infrequently - vertigo, hearing loss.

Cardiac disorders: often - pericardial effusion, arrhythmia (including tachycardia), cardiac dysfunction (including ventricular dysfunction, heart failure, congestive heart failure, cardiomyopathy, congestive cardiomyopathy, diastolic dysfunction, decreased ejection fraction, ventricular failure), palpitations, increased activity of cerebral natriuretic peptide, right ventricular dysfunction, ventricular hypokinesia; infrequently - prolongation of the QT interval on the ECG, angina pectoris, cardiomegaly, pericarditis, ventricular arrhythmia (including ventricular tachycardia), myocardial infarction (including fatal), T wave changes, increased troponin activity; rarely - "pulmonary heart", myocarditis, acute coronary syndrome, cardiac arrest, prolongation of the PR interval, coronary heart disease, pleuropericarditis; frequency unknown - atrial fibrillation/atrial flutter.

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

Disorders of 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 of the gastrointestinal tract: very often - diarrhea, nausea, vomiting, abdominal pain; often - inflammation of the mucous membranes (including mucositis/stomatitis), gastrointestinal bleeding, dyspepsia, bloating, constipation, gastritis, lesions of the soft tissues of the oral cavity (including dry mouth, cheilitis, vesicular rash on the lips, dry lips, ulcers on the lips, erosion of the oral mucosa), colitis (including neutropenic colitis); infrequently - dysphagia, ascites, anal fissures, ulceration of the upper gastrointestinal tract, pancreatitis, esophagitis, gastroesophageal reflux disease; rarely - gastrointestinal enteropathy with loss of protein, intestinal obstruction, acute pancreatitis, anal fistula; frequency unknown - gastrointestinal bleeding with fatal outcome.

Disorders of the liver and biliary tract: infrequently - cholestasis, cholecystitis, hepatitis.

Skin and subcutaneous tissue disorders: 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, hairline changes, neutrophilic dermatosis; rarely - leukocytoclastic vasculitis, skin fibrosis; the frequency is unknown - Stevens-Johnson syndrome.

Disorders of musculoskeletal and connective tissue: very often - musculoskeletal pain; often - arthralgia, muscle weakness, myalgia, musculoskeletal stiffness, muscle spasms; infrequently - rhabdomyolysis, myositis, tendinitis, osteonecrosis, arthritis.

Disorders of the kidneys and urinary tract: infrequently - renal failure, frequent urination, proteinuria, hematuria; rarely - impaired renal function.

Disorders of the genital organs and breast: infrequently - gynecomastia, menstrual disorders, vaginal bleeding, uterine bleeding; rarely - spontaneous abortion.

A complete clinical blood test should be performed weekly in the first 2 months of treatment with Dasatinib-native, and then monthly or more often, according to clinical indications. Bone marrow depression is usually reversible and resolves with temporary withdrawal or reduction of the dose of dasatinib. In patients with newly diagnosed chronic myeloid leukemia, myelosuppression was observed less frequently than in patients in the chronic phase of myeloid leukemia with imatinib resistance or intolerance.

When taking dasatinib, there is evidence of severe cerebral hemorrhages, including fatal ones, reported in less than 1% of patients with imatinib resistance or intolerance treated with dasatinib. Severe gastrointestinal bleeding was observed in 4% of patients with imatinib resistance or intolerance; they usually required temporary withdrawal 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.

Fluid retention may occur when taking dasatinib. 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 reported in 8%, including severe pleural and pericardial effusion in 7% and 1% of patients, respectively. Severe ascites and generalized edema developed in less than 1% of patients with imatinib resistance. Severe pulmonary edema was reported in 1% of patients with imatinib resistance.

In case of shortness of breath, chest pain or dry cough, X-ray monitoring of the chest organs is necessary. Fluid retention is usually stopped with the use of maintenance therapy with the inclusion of diuretics or a short course of glucocorticosteroids. With severe pleural effusion, oxygen therapy and thoracocentesis may be required. Fluid retention is more common in patients taking dasatinib twice a day.

Adverse reactions such as fluid retention, shortness of breath, 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 groups.

Prolongation of the QT interval was observed in less than 1% of patients with newly diagnosed chronic myeloid leukemia in the chronic phase treated with dasatinib, with an average lengthening of 3.0 ms. Prolongation of the QT interval during treatment with dasatinib was observed in more than 1% of patients with resistance or intolerance to imatinib therapy. Dasatinib should be prescribed with caution in patients with an extended QT interval or the risk of its prolongation (hypokalemia, hypomagnesemia, congenital long QT syndrome, therapy with antiarrhythmic and other drugs capable of prolonging the QT interval, previous therapy with high doses of anthracyclines). Before prescribing the drug Dasatinib-native, correction of hypokalemia and hypomagnesemia should be performed to prevent prolongation of the QT interval.

In patients with a history of heart disease or the risk of their development, disorders of the cardiovascular system (pericardial effusion, arrhythmia, palpitations, prolongation of the QT interval, myocardial infarction (including fatal) are more often found among adverse reactions than in other groups of patients. In view of this, in this group of patients, during therapy with Dasatinib-native, it is necessary to carefully monitor the parameters of 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. With an increase in transaminase activity or bilirubin concentration, the dose of Dasatinib-native should be reduced or its intake should be suspended.

When using dasatinib, cases of pulmonary arterial hypertension (PAH) have been described, confirmed by catheterization of the right heart. LAG was noted both during treatment with dasatinib and after a year or more after its completion. Often, in cases of PAH development during treatment with dasatinib, patients had concomitant diseases or during treatment they took dasatinib and other medications at the same time. Before starting treatment with Dasatinib-native, the patient should be examined to identify possible signs and symptoms of heart and lung diseases. If, during treatment with Dasatinib-native, the patient experiences shortness of breath or increased fatigue, it is necessary to exclude the most typical etiology, including pleural effusion, pulmonary edema, anemia and the presence of infiltration in the lungs. At the same time, it is necessary to take into account the recommendations given in the section "Method of administration and doses" for cases of non-hematological adverse reactions: with the development of severe non-hematological adverse reactions, treatment is suspended until the symptoms of the adverse reaction disappear or the patient's condition improves. If no other diagnosis was made during the examination of the patient, the diagnosis of PAH should be taken into consideration. If the patient's PAH is confirmed, treatment with Dasatinib-native should be discontinued without subsequent resumption, ensuring subsequent monitoring of the patient's condition in accordance with standard recommendations. After discontinuation of dasatinib, patients with PAH experienced an improvement in their hemodynamic and clinical parameters.

When taking dasatinib, there were individual cases of severe adverse reactions affecting the skin and mucous membranes, including Stevens-Johnson syndrome and erythema multiforme. In case of such adverse reactions due to taking dasatinib, treatment with Dasatinib-native should be discontinued.

Tyrosine kinase inhibitors BCR-ABL are associated with the reactivation of hepatitis B virus (HBV), isolated cases have been described for dasatinib. In some cases, reactivation of HBV with the use of other tyrosine kinase inhibitors BCR-ABL led to the development of acute liver failure or fulminant hepatitis, and subsequently to liver transplantation or death. Before starting therapy with Dasatinib-native, screening for the presence of HBV should be performed. For patients with positive serological tests, it is recommended to consult a specialist with experience in the treatment of HBV. In patients with HBV carriers who need treatment with BCR-ABL tyrosine kinase inhibitors, it is necessary to monitor clinical and laboratory indicators of HBV activation during therapy and several months after its completion. For patients with reactivated HBV on the background of the use of the drug Dasatinib-native, immediate consultation with a specialist in the treatment of HBV is indicated.

Lactose content

The 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.

Influence on the ability to drive vehicles and mechanisms:

Studies on the effect of dasatinib on the ability to drive vehicles and mechanisms have not been conducted. If the patient notes symptoms associated with treatment with Dasatinib-native, such as dizziness and visual disturbances that affect his ability to concentrate and react quickly, it is recommended to refrain from driving vehicles and mechanisms, as well as from engaging in other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Release form/dosage:

Film-coated tablets, 20 mg, 50 mg, 70 mg, 80 mg, 100 mg, 140 mg.

Packaging:

The dosage is 20 mg, 50 mg, 70 mg. 60 tablets each in polyethylene vials, capped with polyethylene lids with a desiccant, with or without a first opening control ring.

The dosage is 80 mg, 100 mg, 140 mg. 30 tablets each in polyethylene vials, capped with polyethylene lids with a desiccant, with or without a first opening control ring.

A label is affixed to the vials.

1 bottle together with the instructions for use is placed in a cardboard pack.

Storage conditions:

In a place protected from light at a temperature not exceeding 25 ° C.

Keep out of reach of children.

Expiration date:

2 years.