Imatinib (Gleevec)

==General information==
Class/mechanism: Tyrosine kinase inhibitor, inhibits multiple tyrosine kinases, including Bcr-Abl tyrosine kinase, the constitutively active tyrosine kinase resulting from the Philadelphia chromosome abnormality in CML; the receptor tyrosine kinases for platelet-derived growth factor (PDGF), stem cell factor (SCF), and c-kit, which is the activating mutation found in gastrointestinal stromal tumor (GIST) tumors.Imatinib (Gleevec) package insert Imatinib (Gleevec) package insert (locally hosted backup)Gleevec manufacturer's website
Route: PO
Extravasation: n/a
Fertility: evidence of harm Pye SM, Cortes J, Ault P, Hatfield A, Kantarjian H, Pilot R, Rosti G, Apperley JF. The effects of imatinib on pregnancy outcome. Blood. 2008 Jun 15;111(12):5505-8. Epub 2008 Mar 5. link to original article link to PMC article EuroPMC
For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias or the prescribing information. 
==Dose adjustments==
*Strong CYP3A4 inducers: increase starting dose by at least 50%, and carefully monitor
*Mild to moderate hepatic impairment: no adjustment needed
*Severe hepatic impairment: 25% decrease in recommended dose
*Mild renal impairment (CrCl 40 to 59): dose no greater than 600 mg/d
*Moderate renal impairment (CrCl 20 to 39): decrease starting dose by 50%, increase as tolerated but no greater than 400 mg/d
*Severe renal impairment: use with caution
==Diseases for which it is established (work in progress)==
*B-ALL, Ph+
*Chronic myeloid leukemia
*Hypereosinophilic syndrome
*Soft tissue sarcoma
**Dermatofibrosarcoma protuberans (DFSP)
**Gastrointestinal stromal tumor
*Systemic mastocytosis
==Diseases for which it is used==
*Glioblastoma
*Melanoma
*Soft tissue sarcoma
**Desmoid tumors
==Patient drug information==
*Imatinib (Gleevec) package insert
*Imatinib (Gleevec) patient drug information (Chemocare)Imatinib (Gleevec) patient drug information (Chemocare)
*Imatinib (Gleevec) patient drug information (UpToDate)Imatinib (Gleevec) patient drug information (UpToDate)
==History of changes in FDA indication==
===Chronic myeloid leukemia===
*2001-05-10: Initial accelerated approval for the treatment of patients with chronic myeloid leukemia (CML) in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy. (Based on Sawyers et al. 2002, STI571 0109, STIA 0110)
**2003-12-08: Converted to regular approval.
*2002-12-20: Additional accelerated approval for the treatment of newly diagnosed adult patients with Philadelphia chromosome positive chronic myeloid leukemia (CML). (Indication expanded to first-line; based on IRIS)
**2009-05-27: Converted to regular approval.
*2003-05-20: Additional indication for the treatment of pediatric patients with Ph+ chronic phase CML whose disease has recurred after stem cell transplant or who are resistant to interferon alpha therapy. (Indication expanded to the relapsed/refractory pediatric population; based on COG P9973)
*2006-09-27: Additional accelerated approval as a single agent for the treatment of pediatric patients with newly diagnosed Philadelphia chromosome positive chronic myelogenous leukemia (Ph+ CML). (Pediatric indication expanded to first-line; based on COG AAML0123)
**2011-04-01: Converted to regular approval.
===Dermatofibrosarcoma protuberans (DFSP)===
*2006-10-19: Additional indication for adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP). (New disease entity; based on EORTC 62027)
===Gastrointestinal stromal tumor===
*2002-02-01: Accelerated approval for the treatment of patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST). (New disease entity; based on EORTC 62005 & SWOG S0033)
**2008-09-26: Converted to regular approval.
*2008-12-19: Granted accelerated approval for the adjuvant treatment of adult patients following complete gross resection of Kit (CD117) positive gastrointestinal stromal tumor (GIST). (Indication extended to the adjuvant setting; based on ACOSOG Z9001 & SSG XVIII/AIO)
**2012-01-31: Converted to regular approval.
===Hypereosinophilic syndrome (HES)===
*2006-10-19: Additional indications for adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase (mutational analysis or FISH demonstration of CHIC2 allele deletion)
*2006-10-19: Additional indications for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown. (New disease entity)
===Myelodysplastic syndrome===
*2006-10-19: Additional indication for adult patients with myelodysplastic/ myeloproliferative diseases (MDS/MPD) associated with PDGFR (platelet-derived growth factor receptor) gene rearrangements. (New disease entity)
===Ph+ ALL===
*2006-10-19: Additional indication for adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). (New disease entity; based on Ottmann et al. 2002)
*2013-01-25: Additional indication for pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy. (Indication expanded to the first-line pediatric population; based on COG AALL0031)
===Systemic mastocytosis===
*2006-10-19: Additional indication for adult patients with aggressive systemic mastocytosis (ASM) without the D816V c-Kit mutation or with c-Kit mutational status unknown. (New disease entity)
==History of changes in EMA indication==
*2001-11-07: Initial marketing authorization as Glivec.
==History of changes in Health Canada indication==
*2001-09-20: Initial notice of compliance with conditions
*2004-12-29: Conditions were met
==History of changes in PMDA indication==
*2007-01-31: New indication and dosage for treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia.
*2012-02-22: New additional indications and a new dosage for the treatment of FIP1L1-PDGFRα-positive hypereosinophilic syndrome or chronic eosinophilic leukemia.
==Also known as==
*Code names: CGP-57148, CGP-57148B, STI-571
*Generic names: imatinib mesilate, imatinib mesylate
*Brand names: Apotinib, Celonib, Chemotinib, Daxymia, Enliven, Gleevec, Gleevac, Glivec, Glomatinib, Imabak, Imalek, Imarech, Imat, Imatib, Imatinate, Imatirel, Imatikast, Imatova, Imashil, Imasab, Meditinib, Mesylonib, Mitinab, Ontinib, Plivatinib, Samitib, Shantinib, Stritinib, Temsan, Tyronib, Veenat
==References==
Category:Drugs
Category:Oral medications
Category:Mutation-specific medications
Category:Protein expression-specific medications
Category:Bcr-Abl inhibitors
Category:KIT inhibitors
Category:PDGFR inhibitors
Category:B-cell acute lymphoblastic leukemia medications
Category:Chronic myeloid leukemia medications
Category:Dermatofibrosarcoma protuberans medications
Category:Desmoid tumor medications
Category:Glioblastoma medications
Category:Hypereosinophilic syndrome medications
Category:Melanoma medications 
Category:Gastrointestinal stromal tumor medications 
Category:Systemic mastocytosis medications
Category:EMA approved in 2001
Category:FDA approved in 2001
Category:Health Canada approved in 2001
Category:WHO Essential Cancer Medicine