Blood Journal
Leading the way in experimental and clinical research in hematology

Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib

  1. Amina Haouala1,
  2. Nicolas Widmer1,
  3. Michel A. Duchosal2,
  4. Michael Montemurro3,
  5. Thierry Buclin1, and
  6. Laurent A. Decosterd1
  1. 1Division of Clinical Pharmacology and Toxicology,
  2. 2Service and Central Laboratory of Hematology, and
  3. 3Multidisciplinary Oncology Centre, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland

Abstract

Several cancer treatments are shifting from traditional, time-limited, nonspecific cytotoxic chemotherapy cycles to continuous oral treatment with specific protein-targeted therapies. In this line, imatinib mesylate, a selective tyrosine kinases inhibitor (TKI), has excellent efficacy in the treatment of chronic myeloid leukemia. It has opened the way to the development of additional TKIs against chronic myeloid leukemia, including nilotinib and dasatinib. TKIs are prescribed for prolonged periods, often in patients with comorbidities. Therefore, they are regularly co-administered along with treatments at risk of drug-drug interactions. This aspect has been partially addressed so far, calling for a comprehensive review of the published data. We review here the available evidence and pharmacologic mechanisms of interactions between imatinib, dasatinib, and nilotinib and widely prescribed co-medications, including known inhibitors or inducers of cytochromes P450 or drug transporters. Information is mostly available for imatinib mesylate, well introduced in clinical practice. Several pharmacokinetic aspects yet remain insufficiently investigated for these drugs. Regular updates will be mandatory and so is the prospective reporting of unexpected clinical observations.

  • Submitted July 5, 2010.
  • Accepted August 21, 2010.
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