Sprycel (dasatinib) developed by New York-based Bristol-Myers Squibb is an oral inhibitor of multiple tyrosine kinases, for the treatment of adults in all phases of chronic myeloid leukemia with resistance or intolerance to prior therapy, including Gleevec (imatinib mesylate). The success of Sprycel is based on hematologic and cytogenetic response rates. There are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased endurance. The FDA approved Sprycel for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia with resistance or intolerance to prior therapy.

Sprycel (dasatinib) is the first approved oral tyrosine kinase inhibitor expected to bind to multiple conformations of the ABL kinase based on modeling studies. At nanomolar concentrations, Sprycel inhibits BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFR-B. By targeting these kinases, Sprycel inhibits the overproduction of leukemia cells in the bone marrow of patients with CML and Ph+ALL and allows normal red cell, white cell, and blood platelet production to resume.

The FDA reviewed the efficacy and safety of Sprycel based on the analysis of four Phase II multi-center studies in patients with resistance or intolerance to imatinib in all phases of CML or Ph+ ALL. Sprycel is not suggested for use in pregnant women or those contemplating pregnancy. Sprycel (dasatinib) may cause fetal harm. Sexually active male/female patients taking Sprycel must use adequate contraception.

Sprycel is a time-dependent inhibitor of CYP3A4 and drugs that may have their plasma concentration altered by dasatinib are: CYP3A4 substrates with a narrow therapeutic index (e.g., alfentanil, terfenadine, astemizole, cisapride, cyclosporine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, or ergot alkaloids should be administered with caution.