title: Capecitabine-phenytoin interaction is dose dependent with an unexpected time course.
abstract: The main objective of this study was to further analyze the drug interaction between capecitabine and phenytoin with special emphasis on magnitude, timing, and the dose effect. A single patient had multiple phenytoin levels at various doses of capecitabine. Phenytoin levels were subjected to analysis of variance and the dose effect was approached using a multiple comparison test. All phenytoin levels meeting the criteria for steady state were subjected to box plot analysis. Analysis of 35 phenytoin levels over a 25-month period demonstrated a statistically significant interaction between the medications. The interaction onset was delayed by 4 weeks and persisted up to 9 weeks after capecitabine dose increases or decreases. The magnitude of interaction was directly proportional to the capecitabine dosage. We concluded that capecitabine caused a marked increase in phenytoin levels that was capecitine dose dependent, with a delayed time course not predicted by phenytoin kinetics, suggesting a novel interaction mechanism. The magnitude and complexity of this interaction suggest that alternate antiepileptic medications should be used in combination with capecitabine.
authors: Department of Neurology, University of Cincinnati Health Science Center, Ohio 45267-0525, USA. privitmd@ucmail.uc.edu
authors: Michael
authors: M
authors: Privitera
authors: Felipe
authors: F
authors: de Los Ríos la Rosa
mesh_terms: D000368:Aged; D000927:Anticonvulsants / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D010672:Phenytoin / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D000970:Antineoplastic Agents; D003841:Deoxycytidine; D010672:Phenytoin; D000069287:Capecitabine; D005472:Fluorouracil