Drug Interaction Report

MONITOR: Coadministration with febuxostat may alter the pharmacokinetics of theophylline. The proposed mechanism is inhibition of xanthine oxidase by febuxostat. In healthy volunteers, administration of theophylline in combination with febuxostat 80 mg once daily resulted in a 6% increase in theophylline peak plasma concentration (Cmax) and a 6.5% increase in systemic exposure (AUC). These changes were not considered statistically or clinically significant. However, the study also showed an approximately 400-fold increase in the urinary excretion of 1-methylxanthine, one of the major theophylline metabolites. The safety of long-term exposure to 1-methylxanthine has not been evaluated.

MANAGEMENT: No dosage adjustment is necessary for theophylline when coadministered with febuxostat, but caution is advised. Because the safety of long-term exposure to 1-methylxanthine is unknown, this should be taken into consideration when deciding to use the combination.