Class: Tyrosine kinase inhibitor (TKI) – BCR-ABL and SRC family kinase inhibitor
Mechanism of Action
- Inhibits BCR-ABL tyrosine kinase, including many imatinib-resistant mutations (except T315I)
- Also inhibits SRC family kinases, enhancing anti-leukemic activity
Indications
- Chronic Myeloid Leukemia (CML) (chronic, accelerated, and blast phase)
- Philadelphia chromosome-positive Acute Lymphoblastic Leukemia (Ph+ ALL)
- Used in frontline and relapsed/refractory settings
Dosing
- Typical dose for CML chronic phase: 100 mg orally once daily
- Dose adjustments based on toxicity and indication
- Take with or without food; avoid acid-reducing agents if possible
Key Adverse Effects
- Myelosuppression: neutropenia, thrombocytopenia, anemia
- Pleural effusion (common; may be dose-related)
- Pulmonary arterial hypertension (PAH) (rare but serious)
- Bleeding risk (monitor closely if anticoagulated)
- QT prolongation (monitor ECG in high-risk patients)
- Fluid retention, diarrhea, rash, headache
Monitoring
- CBC regularly for cytopenias
- Chest X-ray or CT if symptoms suggest pleural effusion
- ECG if baseline risk or symptoms of arrhythmia
- Liver and renal function tests
- Blood pressure and signs of pulmonary hypertension
Drug Interactions
- Metabolized by CYP3A4: avoid strong inhibitors/inducers
- Acid-reducing agents (PPIs, H2 blockers) reduce absorption; separate administration or avoid PPIs
Other Important Notes