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.