Gleevec
Newly diagnosed adult and pediatric Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase; Ph+ CML in blast crisis, accelerated phase, or chronic phase after failure of interferon-alpha therapy; Ph+ acute lymphoblastic leukemia (ALL); Myelodysplastic/myeloproliferative diseases with PDGFR gene rearrangements; Aggressive systemic mastocytosis without D816V c-Kit mutation; Hypereosinophilic syndrome and/or chronic eosinophilic leukemia with FIP1L1-PDGFRα fusion kinase; Unresectable, recurrent, and/or metastatic dermatofibrosarcoma protuberans (DFSP); Kit (CD117)-positive unresectable and/or metastatic GIST.
CML chronic phase (adults): 400 mg/day orally
CML accelerated/blast: 600 mg/day
Ph+ ALL: 600 mg/day
GIST: 400 mg/day (may increase to 800 mg)
Pediatric CML: 340 mg/m²/day (max 600 mg)
Take with meal and large glass of water to minimize GI irritation. Doses of 800 mg should be administered as 400 mg twice daily.
Tablets: 100 mg, 400 mg
None listed.
- Edema and Fluid Retention: Severe fluid retention (pleural effusion, pericardial effusion, pulmonary edema, ascites) in 2.5%. Periorbital edema in 33%. Weigh regularly.
- Hematologic Toxicity: Neutropenia and thrombocytopenia. Median duration 2-3 weeks. Monitor CBC weekly for first month, biweekly for second month, then periodically.
- Hepatotoxicity: Grade 3-4 elevations in transaminases (5%) or bilirubin (1%). Fatal liver failure and severe hepatotoxicity reported. Monitor LFTs monthly or as needed.
- Cardiac Toxicity: Severe CHF and left ventricular dysfunction reported, particularly in patients with comorbidities.
- GI Toxicity: GI irritation common. Fatal GI hemorrhage/perforation reported, especially in GIST patients.
- Dermatologic Toxicities: Stevens-Johnson syndrome, erythema multiforme reported.
- Growth Retardation: In children. Monitor height.
- Tumor Lysis Syndrome
Edema/fluid retention (60%), nausea (50%), vomiting (28%), muscle cramps (49%), musculoskeletal pain (38%), diarrhea (33%), rash (32%), fatigue (24%), abdominal pain (24%), headache (13%), joint pain (13%)
Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.
Imatinib is a protein-tyrosine kinase inhibitor that inhibits the BCR-ABL tyrosine kinase, the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome (t(9;22)) translocation in CML. It also inhibits the receptor tyrosine kinases for platelet-derived growth factor (PDGFR) and stem cell factor (SCF), c-Kit, and inhibits PDGF- and SCF-mediated cellular events. In vitro, it inhibits proliferation and induces apoptosis in BCR-ABL-positive cell lines.
Tmax: 2-4 hours. Half-life: approximately 18 hours (active metabolite 40 hours). Bioavailability: 98%. Protein binding: 95%. Metabolized primarily by CYP3A4 (active metabolite: N-desmethyl piperazine derivative). Steady-state by Day 7. Excreted in feces (68%) and urine (13%).
Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.
- IRIS — Imatinib vs. interferon-α + cytarabine in newly diagnosed CML. Phase III, n=1106.