Dasatinib

Mechanism :

Dasatinib, at nanomolar concentrations, inhibits the following kinases: BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRß. Based on modelling studies, dasatinib is predicted to bind to multiple conformations of the ABL kinase. In vitro, dasatinib was active in leukemic cell lines representing variants of imatinib mesylate sensitive and resistant disease. Dasatinib inhibited the growth of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines overexpressing BCR-ABL.

Indication :

• Ph+ Chronic Myeloid Leukemia

Contraindications :

Myelosuppression including severe thrombocytopenia, neutropenia and anemia may occur; may manage by dose interruption, dose reduction, or discontinuation of therapy; hematopoietic growth factor has been used with resistant myelosuppression; monitor CBCs weekly for the first 2 months.

CNS and gastrointestinal hemorrhages, including fatalities have occurred; severe hemorrhage may require treatment interruption and transfusion.

Increased risk of developing pulmonary arterial hypertension (PAH); may be reversible on discontinuation; evaluate patients for signs and symptoms of underlying cardiopulmonary disease prior to initiation and during treatment; if PAH confirmed permanently discontinue therapy.

Hypokalemia, hypomagnesemia, congenital QT interval prolongation, hepatic impairment

Use with caution in patients who have or may develop prolongation of QT interval

Cardiac adverse reactions were reported in 5.8% of 258 patients including cardiomyopathy (1.6%), congestive heart failure, diastolic dysfunction, fatal myocardial infarction, and left ventricular dysfunction.

Risk of tumor lysis syndrome.

Risk of fluid retention and pleural/pericardial effusion.

Avoid pregnancy or impregnating women.

Avoid concomitant CYP3A4 inducers/inhibitors.

Dosing :

Adverse Effect :

Fluid retention, diarrhea, headache, hemorrhage, fatigue, pyrexia, skin rash, infection, nausea, dyspnea, cough, pain, abdominal pain, vomiting, anorexia, arthralgia, asthenia, constipation, dizziness, musculoskeletal pain, weight loss, chest pain, neuropathy, myalgia, abdominal distention, arrhythmia, chills, pruritus, weight gain, anemia, febrile neutropenia, thrombocytopenia, mucosal inflammation.

Interaction :

CYP3A4 Inhibitors: Increase plasma concentrations and inducers decrease plasma concentrations.
Proton-pump inhibitor: Absorption decreased by PPI.

Renal Dose :

Hepatic Dose :