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Absorption
T max is between 0.5 and 6 h.
Distribution
Vd is 2,505 L, suggesting extensive distribution in extravascular space. Protein binding 96%; active metabolite 93%.
Metabolism
Extensively metabolized by CYP3A4 to an active metabolite, which is equipotent to dasatinib. Also metabolized by flavin-containing monooxygenase-3 and uridine diphosphate-glucuronosyltransferase enzymes.
Elimination
Terminal half-life is 3 to 5 h. Excretion is primarily fecal (85%) and 4% in urine.
Special Populations
Renal Function Impairment
There are no studies in patients with impaired renal function; however, only 4% of the drug and its metabolites are excreted by the kidney.
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Antacids
Based on nonclinical data, if antacid therapy cannot be avoided, administer the antacid at least 2 h before or after dasatinib.
CYP3A4 inducers (eg, carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, St. John's wort)
May reduce dasatinib plasma levels, decreasing the therapeutic effect. When possible, use alternative therapy.
CYP3A4 inhibitors (eg, atazanavir, clarithromycin, erythromycin, grapefruit juice, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole)
May elevate dasatinib plasma concentrations, increasing the risk of adverse reactions.
CYP3A4 substrates (eg, alfentanil, astemizole, cisapride, cyclosporine, ergot alkaloids, fentanyl, pimozide, quinidine, simvastatin, sirolimus, tacrolimus, terfenadine)
Plasma levels may be altered by dasatinib; therefore, use with caution.
H2 antagonists (eg, famotidine), proton pump inhibitors (eg, omeprazole)
May reduce dasatinib plasma levels, decreasing the therapeutic effect. Concommitant use is not recommended.
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