dasatinib — Drug Monograph

Brand names: Sprycel

Drug class: Tyrosine Kinase Inhibitor

Mechanism of Action

Dasatinib is a potent, second-generation BCR-ABL tyrosine kinase inhibitor that also inhibits SRC-family kinases (SFK: SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFR-β. It binds the BCR-ABL kinase domain in both active and inactive conformations, achieving approximately 325-fold greater potency against BCR-ABL compared to imatinib in vitro. The dual BCR-ABL/SFK inhibition is clinically meaningful because SRC kinases can activate BCR-ABL–independent signaling pathways that contribute to imatinib resistance. Dasatinib retains activity against most imatinib-resistant BCR-ABL point mutations with…

FDA Indications

• Chronic myeloid leukemia (CML) — chronic phase (CP-CML), accelerated phase (AP-CML), and blast phase (BP-CML) with resistance or intolerance to prior therapy including imatinib — approved 2006
• Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) with resistance or intolerance to prior therapy — approved 2006
• Newly diagnosed CP-CML (frontline) — approved 2010 (DASISION trial)
• Pediatric patients with Ph+ CML (CP) or Ph+ ALL — approved 2017 (CA180-226 trial)

Common Side Effects

• Myelosuppression — neutropenia (36%), thrombocytopenia (35%), anemia (13%)
• Fluid retention — superficial edema (21%), pleural effusion (28%)
• Diarrhea (27%)
• Headache (33%)
• Fatigue (24%)
• Nausea (24%)
• Rash (17%)
• Musculoskeletal pain (13%)
• Dyspnea (20%)
• Hemorrhage (mostly superficial/mucocutaneous, 11%)
• Infection (11%)

Clinical Pearl

Dasatinib's superior CNS penetration compared to imatinib or nilotinib makes it a preferred second-generation TKI in patients with CNS involvement in Ph+ ALL or CML blast phase. Once-daily 100 mg dosing (versus the original 70 mg BID schedule) achieves equivalent efficacy with significantly lower rates of pleural effusion (~14% vs ~28%), making adherence and tolerability more favorable. Pleural effusion management typically involves dose interruption, short-course corticosteroids, and…

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