title: A clinically relevant pharmacokinetic interaction between cyclosporine and imatinib.
abstract: OBJECTIVE
  Cyclosporine A (CsA) and imatinib are both CYP3A4 and P-glycoprotein substrates. Concomitant use after hematopoietic stem cell transplantation (HSCT) for chronic myeloid leukemia (CML) or Philadelphia chromosome-positive (Ph+) acute lymphatic leukemia (ALL) may therefore result in a pharmacokinetic interaction. Although case reports and a recent small study in children indeed suggested there is a relevant pharmacokinetic interaction, a larger study in adults is lacking. In this study, we assessed the presence and extent of this interaction in patients with CML or Ph+ ALL undergoing HSCT.
  
  
  METHODS
  From a large database containing data of all patients receiving HSCT in our center between 2005 and 2015, we selected 16 patients using this drug combination. The average dose-corrected CsA concentration was calculated before and after initiation of imatinib.
  
  
  RESULTS
  The average dose-corrected CsA concentration increased during imatinib use in all patients, on average by 94 % (p < 0.001). Based on measured drug concentrations, the CsA dosage needed to be reduced, on average, by 27 % after initiation of imatinib (p = 0.004).
  
  
  CONCLUSIONS
  Imatinib significantly increases CsA concentrations in HSCT patients, putting these patients at increased risk of CsA toxicity. We recommend intensive monitoring of CsA concentrations after initiation of imatinib; a pre-emptive CsA dose reduction of 25 % might be considered.
authors.affiliation: Department of Hospital Pharmacy, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Ferdows
authors.initials: F
authors.lastname: Atiq
authors.affiliation: Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Annoek E C
authors.initials: AE
authors.lastname: Broers
authors.affiliation: Department of Hospital Pharmacy, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Louise M
authors.initials: LM
authors.lastname: Andrews
authors.affiliation: Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Jeanette K
authors.initials: JK
authors.lastname: Doorduijn
authors.affiliation: Department of Hospital Pharmacy, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Birgit C P
authors.initials: BC
authors.lastname: Koch
authors.affiliation: Department of Hospital Pharmacy, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Internal Medicine, Erasmus Medical Center, PO Box 2040, 3000, CA, Rotterdam, The Netherlands.
authors.forename: Teun
authors.initials: T
authors.lastname: Van Gelder
authors.affiliation: Department of Internal Medicine, Erasmus Medical Center, PO Box 2040, 3000, CA, Rotterdam, The Netherlands. j.versmissen@erasmusmc.nl.
authors.forename: Jorie
authors.initials: J
authors.lastname: Versmissen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004347:Drug Interactions; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology* / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; D016572:Cyclosporine; D000068877:Imatinib Mesylate
keywords: Cyclosporine; Graft-versus-host disease; Hematopoietic stem cell transplantation; Imatinib