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imatinib (Gleevec)

Tradename: Gleevec (imatinib mesylate), formerly STI571 Indications: - chronic myeloid leukemia* (CML) [2,3,4,9] - Philadelphia chromosome-positive ALL [10] - chronic eosinophilic leukemia - hypereosinophilic syndrome [10] - lung cancer - gastrointestinal stromal tumor - pancreatic cancer [9] - dermatofibrosarcoma protuberans [10] - systemic mastocytosis [10] - scleroderma ? [12] * may be drug of choice for CML Dosage: given PO QD Monitor: - complete blood count (CBC) - liver function tests (serum AST, serum ALT serum alkaline phosphatase) baseline, monthly, & as clinically indicated [7] * also see ARUP consult [] Adverse effects: 1) edema 2) nausea 3) muscle cramps 4) neutropenia 5) thrombocytopenia 6) severe congestive heart failure [6] - left ventricular dysfunction 7) hepatotoxicity [7] 8) rash 9) fatigue 10) diarrhea [9] * adverse effects severe enough to cause discontinuation of therapy in 2% of patients [2] Mechanism of action: 1) binds to & blocks ABL1 & ABL2 that stimulates proliferation of abnormal leukocytes (including BCR-ABL) 2) binds to different site than BMS-354825 3) inhibits CSF1R 4) inhibits EGFR [9] 5) inhibits GSAP, thus may inhibit beta-amyloid production [11] Notes: - Manufacturer: Novartis - price tripled from $30,000 per year in the U.S. at its 2001 introduction to over $90,000 in 2012 [8]

Interactions

drug adverse effects of tyrosine kinase inhibitor(s)

General

antineoplastic tyrosine kinase inhibitor small inhibitory antineoplastic agent (ib drug)

Properties

INHIBITS: P210-BCR-ABL

Database Correlations

PUBCHEM correlations

References

  1. Prescriber's Letter 8(6):34 2001
  2. Journal Watch 22(7):53, 2002 Kantarjian H et al, N Engl J Med 346:645, 2002 Savage DG & Antman KH, N Engl J Med 346:683, 2002
  3. Journal Watch 21(9):72, 2001 Druker et al, N Engl J Med 344:1031, 2001 Druker et al, N Engl J Med 344:1038, 2001 Goldman & Melo, N Engl J Med 344:1084, 2001
  4. Journal Watch 23(8):63-64, 2003 O'Brien SG et al, N Engl J Med 348:994, 2003 Pegg K & Mackinnon S, N Engl J Med 348:1048, 2003
  5. Department of Veterans Affairs, VA National Formulary - restricted to hematology/oncology
  6. FDA MedWatch http://www.fda.gov/medwatch/safety/2006/safety06.htm#Gleevec
  7. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: 260704 (subscription needed) http://www.prescribersletter.com
  8. Experts in chronic myeloid leukemia Price of drugs for chronic myeloid leukemia (CML), reflection of the unsustainable cancer drug prices: perspective of CML experts. Blood. April 15, 2013 PMID: 23620577 http://bloodjournal.hematologylibrary.org/content/early/2013/04/23/blood-2013-03-490003.full.pdf+html
  9. Medical Knowledge Self Assessment Program (MKSAP) 16, 18. American College of Physicians, Philadelphia 2012, 2018.
  10. Deprecated Reference
  11. He G, Luo W, Li P, Remmers C Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease. Nature. 2010 Sep 2;467(7311):95-8 PMID: 20811458
  12. Spiera RF, Gordon JK, Mersten JN et al Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial. Ann Rheum Dis. 2011 Jun;70(6):1003-9. PMID: 21398330
  13. ARUP Consult: Imatinib Therapeutic Drug Monitoring https://arupconsult.com/ati/imatinib-therapeutic-drug-monitoring