Glivec

Glivec is the EU trade name for imatinib mesylate (sold as Gleevec in the US). FDA-approved indications include: CML: Adults newly diagnosed with Philadelphia chromosome-positive (Ph+) CML in chronic phase; chronic phase, accelerated phase, or blast crisis CML after failure of interferon-alpha therapy. GIST: Adjuvant treatment of adult patients following complete gross resection of Kit (CD117)-positive GIST; unresectable and/or metastatic malignant GIST. Ph+ ALL: Adults with relapsed or refractory Ph+ ALL. MDS/MPD: With PDGFR gene rearrangements. ASM: Aggressive systemic mastocytosis without D816V c-Kit mutation or unknown c-Kit status. HES/CEL: Hypereosinophilic syndrome and/or chronic eosinophilic leukemia. DFSP: Dermatofibrosarcoma protuberans, unresectable, recurrent, or metastatic.

CML chronic phase: 400 mg/day orally.
CML accelerated phase/blast crisis: 600 mg/day.
GIST adjuvant: 400 mg/day for 3 years.
GIST unresectable/metastatic: 400 mg/day (may increase to 400 mg twice daily for disease progression).
Ph+ ALL: 600 mg/day.
Take with food and large glass of water. May increase to 600–800 mg/day for insufficient response in CML. Dose adjustments for renal/hepatic impairment required.

Tablets: 100 mg, 400 mg

None established in prescribing information.

• Fluid Retention / Edema: Severe fluid retention (pleural effusion, pericardial effusion, pulmonary edema, ascites) in up to 3.5% of patients. Monitor weight and manage promptly.
• Hematologic Toxicity: Grade 3–4 neutropenia and thrombocytopenia. Monitor CBC at baseline, weekly for first month, biweekly for second month, then periodically.
• Hepatotoxicity: Severe liver toxicity including liver failure and liver necrosis. Monitor liver function tests.
• Cardiac Toxicity: Cardiomyopathy and cardiac failure reported, especially in patients with comorbidities.
• Dermatologic Reactions: Severe bullous reactions including Stevens-Johnson syndrome reported.
• Growth Retardation in Pediatric Patients: Monitor growth in children.
• Hypothyroidism: In thyroidectomy patients on levothyroxine — monitor TSH.
• Embryo-Fetal Toxicity: Can cause fetal harm. Advise effective contraception.

Nausea (73%), Fluid Retention/Edema (72%), Muscle cramps (62%), Diarrhea (43%), Fatigue (39%), Rash (40%), Neutropenia (48%), Thrombocytopenia (30%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin): Increase imatinib levels ~40%; monitor for toxicity.
Strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin): Decrease imatinib levels by ~74%; avoid or increase imatinib dose.
Warfarin: Imatinib inhibits CYP2C9; use low-molecular-weight heparin instead; monitor INR if warfarin used.
Simvastatin: CYP3A4 substrate — increased exposure with imatinib.

Can cause fetal harm. Advise females of reproductive potential to use effective contraception. Consult the full prescribing information for pregnancy risk details.

Advise women not to breastfeed during treatment and for a period after the last dose. Refer to prescribing information for duration guidance.

Safety and effectiveness in pediatric patients have not been established unless otherwise noted in the full prescribing information.

Dose modifications for organ impairment are specified in the complete prescribing information.

Imatinib mesylate is a competitive inhibitor of BCR-ABL tyrosine kinase, the constitutively active fusion protein formed by the Philadelphia chromosome translocation t(9;22). It also inhibits KIT (CD117) and PDGFR receptor tyrosine kinases. By blocking ATP binding in the kinase domain, imatinib prevents phosphorylation and activation of substrates involved in cell proliferation and survival.

Tmax: 2–4 hours. Bioavailability: 98%. Protein binding: ~95% (mainly albumin). Metabolized primarily by CYP3A4 to active N-desmethyl metabolite (CGP74588, ~15% activity of parent). Parent half-life: ~18 hours; metabolite: ~40 hours. Fecal elimination: ~68%; urinary: ~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-alfa + cytarabine in newly diagnosed Ph+ CML chronic phase. Phase III, n=1106.
  📄 Primary Publication ↗
• B2222 — Imatinib in metastatic or unresectable GIST. Phase II.
  📄 Primary Publication ↗
• ACOSOG Z9001 — Adjuvant imatinib vs placebo following resection of KIT-positive GIST. Phase III, n=713.
  🔬 NCT00041197 ↗📄 Primary Publication ↗

Glivec has FDA-approved indications across the following cancer types covered on CancerDrugEvidence: