Description
Dasatinib is an oral BCR-ABL tyrosine kinase inhibitor use to treat Chronic Myeloid Leukemiamia and Ph+ Acute Lymphoblastic Leukemia.
Dasatinib use to treat a various type of chronic myeloid leukemia (CML; a type of cancer of the white blood cells) as a first treatment in man and women who can no longer benefit from other leukemia medications including imatinib (Gleevec) or in those who cannot take these medications because of side effects. Dasatinib also use to treat a various type of chronic CML in children. Dasatinib further also use to treat a various type of acute lymphoblastic leukemia (ALL; a type of cancer of the white blood cells) in man and women who can no longer benefit from other leukemia medications or who cannot take these medications because of side effects. Dasatinib like a class of medications call kinase inhibitors. It blocks the action of an abnormal protein that signals cancer cells to multiply.
Indications
Newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase.Chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib.Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy.
Pharmacology Dasatinib
Dasatinib, at nanomolar concentrations, inhibits the following kinases: BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ. Based on modeling studies, dasatinib predict 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. Under the conditions of the assays, dasatinib was able to overcome imatinib resistance resulting from BCR-ABL kinase domain mutations, activation of alternate signaling pathways involving the SRC family kinases (LYN, HCK), and multi-drug resistance gene overexpression.
Dosage & Administration Dasatinib
Chronic phase CML is 100 mg administered orally once daily. Accelerated phase CML, myeloid or lymphoid blast phase CML, or Ph+ ALL is 140 mg administer orally once daily.Tablets not to crush or cut; they swallowed whole. Dasatinib need to taken with or without a meal, either in the morning or in the evening.
In clinical studies, treatment with Dasatinib continue until disease progression or until no longer tolerated by the patient. The effect of stopping treatment on long-term disease outcome after the achievement of a cytogenetic response (including complete cytogenetic response [CCyR]) or major molecular response (MMR) is not known.
Interaction
Concomitant use with drugs that have narrow therapeutic index (e.g. alfentanil, cisapride, ciclosporin, fentanyl, pimozide, quinidine, simvastatin, sirolimus, tacrolimus, ergot alkaloids) as it may increase the serum levels of these drugs. Increased risk of bleeding and thrombocytopenia with antiplatelet drugs, anticoagulants, and NSAIDs.
Contraindications
Concomitant use with CYP3A4 inhibitors (e.g. atazanavir, clarithromycin, erythromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole or grapefruit juice); CYP3A4 inducers (e.g. carbamazepine, dexamethasone, phenytoin, phenobarbital, rifampicin or St John’s wort); antacid. Pregnancy.
Side Effects
Pregnancy & Lactation
Precautions & Warnings
Use in Special Populations
Pediatric Use: The safety and efficacy of Dasatinib in patients less than 18 years of age not to establish.
Geriatric Use: No differences in confirmed Complete Cytogenetic Response (cCCyR) and MMR observed between older and younger patients. Of the 2712 patients in clinical studies of Dasatinib, 617 (23%) were 65 years of age and older, and 123 (5%) were 75 years of age and older. While the safety profile of Dasatinib in the geriatric population was similar to that in the younger population, patients aged 65 years and older are more likely to experience the commonly reported adverse reactions of fatigue, pleural effusion, diarrhea, dyspnea, cough, lower gastrointestinal hemorrhage, and appetite disturbance, and more likely to experience the less frequently reported adverse reactions of abdominal distention, dizziness, pericardial effusion, congestive heart failure, hypertension, pulmonary edema, and weight decrease, and should be monitored closely.
Hepatic Impairment: No dosage adjustment is necessary in patients with hepatic impairment. Caution recommended when administering Dasatinib to patients with hepatic impairment.
Renal Impairment: There are currently no clinical studies with Dasatinib in patients with impaired renal function. Less than 4% of dasatinib and its metabolites excreted via the kidney.
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