Overview
11 DESCRIPTION Dasatinib tablets are a kinase inhibitor. The chemical name for dasatinib is N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide, monohydrate. The molecular formula is C 22 H 26 ClN 7 O 2 S • H 2 O, which corresponds to a formula weight of 506.02 (monohydrate). The anhydrous free base has a molecular weight of 488.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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 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.
Indications
- 1 INDICATIONS AND USAGE Dasatinib tablets are indicated for the treatment of adult patients with 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. Dasatinib tablets are indicated for the treatment of pediatric patients 1 year of age and older with Ph+ CML in chronic phase.
Common Doses
- 100 mg
- 140 mg
- 40 mg
- 60 mg
Dosage
2 DOSAGE AND ADMINISTRATION Chronic phase CML in adults: 100 mg once daily. ( 2 ) Accelerated phase CML, myeloid or lymphoid blast phase CML, or Ph+ ALL in adults: 140 mg once daily. ( 2 ) Chronic phase CML and ALL in pediatrics: starting dose based on body weight. ( 2 ) Administer orally, with or without a meal. Do not crush, cut, or chew tablets. ( 2 ) 2.1 Dosage of Dasatinib Tablets in Adult Patients The recommended starting dosage of dasatinib tablets for chronic phase CML in adults is 100 mg administered orally once daily.
Contraindications
- 4 CONTRAINDICATIONS None. None. (4)
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: • Myelosuppression [see Dosage and Administration (2.5) and Warnings and Precautions (5.1) ] . • Bleeding-related events [see Warnings and Precautions (5.2) ] . • Fluid retention [see Warnings and Precautions (5.3) ] . • Cardiovascular toxicity [see Warnings and Precautions (5.4) ] . • Pulmonary arterial hypertension [see Warnings and Precautions (5.5) ] . • QT prolongation [see Warnings and Precautions (5.6) ] .
Interactions
- 7 DRUG INTERACTIONS Strong CYP3A4 Inhibitors: Dose reduction may be necessary. ( 2.3 , 7.1 ) Strong CYP3A4 Inducers: Dose increase may be necessary. ( 2.3 , 7.1 ) Antacids: Avoid simultaneous administration. ( 7.1 ) H 2 Antagonists and Proton Pump Inhibitors: Avoid coadministration. ( 7.1 ) 7.1 Effect of Other Drugs on Dasatinib Strong CYP3A4 Inhibitors The coadministration with strong CYP3A inhibitors may increase dasatinib concentrations [ see Clinical Pharmacology (12.3) ] . Increased dasatinib concentrations may increase the risk of toxicity.