Indications | First-line therapy (CP, AP, BP); relapsed/ refractory Ph+ ALL | First-line therapy (CP), resistance or intolerance to imatinib (CP and AP) | First-line therapy (CP), resistance or intolerance to other TKIs (CP, AP, or BP); Ph+ ALL with resistance or intolerance to prior therapy | Second-line therapy (CP, AP, BP with resistance or intolerance) | Resistance or intolerance to prior TKI or Ph+ ALL resistant or intolerant to all other TKIs; all T315I + casesI |
Usual dosing | CP 400 mg/d AP/BP/progression 600–800 mg/d | CP 300 mg twice daily AP/BP 400 mg twice daily | CP 100 mg/d AP/BP 140 mg/d | 500 mg/d | 45 mg/d |
Common toxicities (nonhematologic) | GI disturbance, edema (including periorbital), muscle cramps, arthralgias, Hypophosphatemia, rash | Rash, GI disturbances, elevated lipase, hyperglycemia, low phosphorus, increased LFTs | Edema, pleural effusions, GI symptoms, rash, low phosphorus | GI (diarrhea), rash, edema, fatigue, low phosphorus, elevated LFTs | HBP, rash, GI, fatigue, headache |
Other significant toxicities | Elevated LFTs (usually appear in first month); rare cardiac toxicity reported | Peripheral vascular disease, PT prolongation, pancreatitis | Pulmonary arterial hypertension, QTc prolongation | | Arterial and venous thrombosis, pancreatitis, liver failure, ocular toxicity, cardiac failure |
Drug–drug interactions | CYP3A4 inducers decrease levels CYP3A4 inhibitors may increase levels It is an inhibitor of CYP3A4 and CYP2D6 Pgp substrate | CYP3A4 inhibitors increase levels CYP3A4 inducers may decrease levels Inhibitor of CYP3A4, CYP2C8, CYP2C9, CYP2D6 Induces CYP2B6, CYP2C8, and CYP2C9 | CYP3A4 inhibitors increase levels CYP3A4 inducer decrease levels Antacids decrease levels H2 antagonists/ proton pump inhibitors decrease levels | CYP3A inhibitors and inducers may alter levels Acid-reducing medication may lower levels | Strong CYP3A inhibitors increased serum levels |
Administration considerations | Taken with food | Taken on empty stomach; avoid food 2 hours before and 2 hours after dose | Can be taken with or without a meal | Taken with food | Taken with and without food |
Black Box Warnings | None | QT prolongation and sudden death | None | None | Arterial thrombosis; hepatotoxicity |
Other considerations | Approved in pediatric patients (340 mg/m2/d) in CP | Keep potassium, Mg, calcium, phosphorus repleted | Ascites and pericardial effusion can also occur; has CSF penetration | | Has activity with T315I mutations; Available in United States through ARIAD PASS program |