title: Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib.
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.
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Amina
authors.initials: A
authors.lastname: Haouala
authors.forename: Nicolas
authors.initials: N
authors.lastname: Widmer
authors.forename: Michel A
authors.initials: MA
authors.lastname: Duchosal
authors.forename: Michael
authors.initials: M
authors.lastname: Montemurro
authors.forename: Thierry
authors.initials: T
authors.lastname: Buclin
authors.forename: Laurent A
authors.initials: LA
authors.lastname: Decosterd
mesh_terms: D000970:Antineoplastic Agents; D001549:Benzamides; D000069439:Dasatinib; D004347:Drug Interactions; D006801:Humans; D000068877:Imatinib Mesylate; D010879:Piperazines; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines; D013844:Thiazoles
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; C498826:nilotinib; D000069439:Dasatinib