Imatinib (Gleevec)

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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.[1][2][3]
Route: PO
Extravasation: n/a
Fertility: evidence of harm [4]

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 such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.[1]

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 used

Patient drug information

History of changes in FDA indication

Chronic myelogenous leukemia

Dermatofibrosarcoma protuberans (DFSP)

Gastrointestinal stromal tumor

  • 2/1/2002: Approved for the treatment of patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST). (New disease entity)
  • 12/19/2008: 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)
  • 1/31/2010: Granted regular approval for the adjuvant treatment of adult patients following complete gross resection of Kit (CD117) positive gastrointestinal stromal tumor (GIST). (Converted from accelerated to regular approval)

Hypereosinophilic syndrome (HES)

Myelodysplastic syndrome

Ph+ ALL

Systemic mastocytosis

Also known as

  • Code names: CGP 57148, CGP57148B, STI-571
  • Generic names: imatinib mesilate, imatinib mesylate
  • Brand names: Enliven, Glivec, Gleevac, Gleevec, Imalek, Imatib, Temsan, Veenat

References

  1. 1.0 1.1 Imatinib (Gleevec) package insert
  2. Imatinib (Gleevec) package insert (locally hosted backup)
  3. Gleevec manufacturer's website
  4. 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 PubMed
  5. Imatinib (Gleevec) patient drug information (Chemocare)
  6. Imatinib (Gleevec) patient drug information (UpToDate)