Effect of Grapefruit Juice on the Pharmacokinetics of Nilotinib in Healthy Participants

Nilotinib (Tasigna; Novartis Pharmaceuticals) is a second‐generation BCR‐ABL tyrosine kinase inhibitor newly approved for the treatment of imatinib‐resistant or imatinib‐intolerant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia in chronic phase or accelerated phase. This study evaluated the effect of grapefruit juice on the pharmacokinetics of nilotinib in 21 healthy male participants. All participants underwent 2 study periods during which they received a single oral dose of 400 mg nilotinib with 240 mL double‐strength grapefruit juice or 240 mL water in a crossover fashion. Serial blood samples were collected for the determination of serum nilotinib concentrations by a validated liquid chromatography/tandem mass spectrometry assay. Concurrent intake of grapefruit juice increased the nilotinib peak concentration (Cmax) by 60% and the area under the serum concentration‐time curve (AUC>0–∞) by 29% but did not affect the time to reach Cmax or the elimination half‐life of nilotinib. The most common adverse events were headache and vomiting, which were mild or moderate in severity, and their frequency appeared to be similar between 2 treatments. Based on the currently available information about nilotinib and the observed extent of increase in nilotinib exposure, concurrent administration of nilotinib with grapefruit juice is not recommended.