Comparative Pharmacology
Head-to-head clinical analysis: GILOTRIF versus GLEEVEC.
Peer-Reviewed Evidence
Head-to-head clinical analysis: GILOTRIF versus GLEEVEC.
GILOTRIF vs GLEEVEC
Comparing the clinical profiles, pharmacokinetic behaviors, and safety indices of these two therapeutic agents.
GILOTRIF (afatinib) is an irreversible inhibitor of the ErbB family of tyrosine kinases, including EGFR (ErbB1), HER2 (ErbB2), ErbB3, and ErbB4. It binds covalently to the ATP-binding pocket of the kinase domain, blocking downstream signaling pathways involved in cell proliferation, survival, and angiogenesis.
Imatinib mesylate is a tyrosine kinase inhibitor that selectively inhibits BCR-ABL, c-KIT, PDGFR, and other kinases, blocking proliferation and inducing apoptosis in cells expressing these targets.
40 mg orally once daily for first-line treatment of EGFR mutation-positive non-small cell lung cancer; may be increased to 50 mg if tolerated.
400 mg orally once daily with a meal and a large glass of water. For advanced GIST, 400 mg daily; for CML in chronic phase, 400 mg daily; for accelerated phase or blast crisis, 600 mg daily. Dose may be increased to 600 mg or 800 mg daily in patients with disease progression.
None Documented
None Documented
Terminal elimination half-life is approximately 41 hours, supporting once-daily dosing. Steady-state is reached within 8 days.
Terminal elimination half-life is approximately 18 hours (range 13–20 hours) in healthy subjects; for the active N-desmethyl metabolite, half-life is about 40 hours (range 30–50 hours). Clinical context: Steady-state is achieved within 1–2 weeks; once-daily dosing maintains therapeutic concentrations.
Approximately 88% of the administered dose is eliminated via feces (with 85% as unchanged parent drug), and 8% via urine (with <5% as unchanged drug). Biliary excretion is the primary route for unchanged drug.
Primarily fecal (68% of dose) as metabolites; renal excretion accounts for approximately 13% of dose (predominantly as metabolites). Unchanged imatinib in urine is <10%.
Category C
Category C
Tyrosine Kinase Inhibitor
Tyrosine Kinase Inhibitor