Imatinib | BCR-ABL, c-Kit, platelet-derived growth factor receptor (PDGFR) | 98% bioavailability; transport via OCT-1 | Hepatic; dose adjustments for severe hepatic and renal impairment | 18 hours | Once daily at 400–800 mg | CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine) CYP3A4 inhibitors (eg, aprepitant, clarithromycin, itraconazole) | Dose-related fluid retention, heart failure, hepatotoxicity, nausea and vomiting, diarrhea, abdominal pain, skin reactions, myelosuppression |
Dasatinib | BCR-ABL, c-Kit, PDGFR, Src family kinases | pH-dependent absorption | Hepatic | 3–5 hours | Once daily at 100 mg or twice daily at 70 mg | CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine) CYP3A4 inhibitors (eg, aprepitant, clarithromycin, itraconazole) Antacids, H2 blockers, proton pump inhibitors | Fluid retention (> 20%) including pleural and pericardial effusions, heart failure, hepatotoxicity, nausea and vomiting, diarrhea, abdominal pain, skin reactions, myelosuppression, QT prolongation (in vitro), hypocalcemia, hypophosphatemia |
Nilotinib | BCR-ABL, c-Kit, PDGFR | Increased bioavailability if taken with food | Hepatic | 17 hours | Twice daily at 400 mg | CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine) CYP3A4 inhibitors (eg, aprepitant, clarithromycin, itraconazole) Drugs that prolong the QT interval | Fluid retention, heart failure, hepatotoxicity, nausea and vomiting, diarrhea, abdominal pain, skin reactions, myelosuppression, QT prolongation, hypocalcemia, hypophosphatemia, elevated serum lipase and amylase |
Bosutinib | BCR-ABL, SRC, LYN, HCK | Absorption may be affected by magnesium intake | Hepatic; dose adjustments for severe hepatic and renal impairment | 22 hours | Once daily at 500–600 mg | CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine) CYP3A4 inhibitors (eg, aprepitant, clarithromycin, itraconazole) Antacids, H2 blockers, proton pump inhibitors | Myelosuppression, skin reactions, QT prolongation, Fluid retention, diarrhea, hypophosphatemia, hyper-/hypomagnesemia |
Ponatinib | BCR-ABL (including T315I), VEGFR, PDGFR, FGFR, SRC, KIT, RET, TIE-2, FLT-3 | pH-dependent absorption | Hepatic | 24 hours | Once daily at 30–45 mg | CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine) CYP3A4 inhibitors (eg, aprepitant, clarithromycin, itraconazole) Ponatinib is an inhibitor of ABCG2 and P-glycoprotein | Arterial thrombosis, hepatotoxicity, gastrointestinal perforation, wound healing complications, hemorrhage, myelosuppression, cardiac arrhythmias, pancreatitis |