DASATINIB

The pharmacokinetics of dasatinib exhibits dose proportional increases in AUC and linear elimination characteristics over the dose range of 15 mg/day (0.15 times the lowest approved recommended dose) to 240 mg/day (1.7 times the highest approved recommended dose). At 100 mg QD, the maximum concentration at steady state (C max ) is 82.2 ng/mL (CV% 69%), area under the plasma drug concentration time curve (AUC) is 397 ng/mL*hr (CV% 55%). The clearance of dasatinib is found to be time-invariant. Wh...

14.1 Newly Diagnosed Chronic Phase CML in Adults DASISION (Dasatinib vs Imatinib Study in Treatment-Naive Chronic Myeloid Leukemia Patients) (NCT00481247) was an open-label, multicenter, international, randomized trial conducted in adult patients with newly diagnosed chronic phase CML. A total of 519 patients were randomized to receive either dasatinib 100 mg once daily or imatinib 400 mg once daily. Patients with a history of cardiac disease were included in this trial except those who had a myocardial infarction within 6 months, congestive heart failure within 3 months, significant arrhythmi...

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 [...

None. None. (4)

Myelosuppression and Bleeding Events: Severe thrombocytopenia, neutropenia, and anemia may occur. Use caution if used concomitantly with medications that inhibit platelet function or anticoagulants. Monitor complete blood counts regularly. Transfuse and interrupt dasatinib tablets when indicated. ( 2.5 , 5.1 , 5.2 ) Fluid Retention: Fluid retention, sometimes severe, including pleural effusions. Manage with supportive care measures and/or dose modification. ( 2.5 , 5.3 ) Cardiovascular Toxicity:...

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 inhib...