RiteMED Febuxostat Drug Interactions

Mercaptopurine/Azathioprine: Although interaction studies with FEBUXOSTAT have not been performed, inhibition of xanthine oxidase (XO) is known to result in an increase in mercaptopurine or azathioprine levels. On the basis of the mechanism of action of FEBUXOSTAT on XO inhibition concomitant use is not recommended. Drug interaction studies of FEBUXOSTAT with cytotoxic chemotherapy have not been conducted. No data is available regarding the safety of FEBUXOSTAT during cytotoxic therapy.
Theophylline: Although interaction studies have not been performed with FEBUXOSTAT, inhibition of XO may cause an increase in the theophylline level (inhibition of the metabolism of theophylline has been reported with other XO inhibitors). Hence caution is advised if these active substances are given concomitantly, and theophylline levels should be monitored in patients starting FEBUXOSTAT therapy.
Naproxen and other inhibitors of glucuronidation: FEBUXOSTAT metabolism depends on UGT enzymes. Medicinal products that inhibit glucuronidation, such as NSAIDs and probenecid, could in theory affect the elimination of FEBUXOSTAT. In healthy subjects concomitant use of FEBUXOSTAT and naproxen 250 mg BID was associated with an increase in FEBUXOSTAT exposure (C_max 28%, AUC 41% and T_1/2 26%). In clinical studies the use of naproxen or other NSAIDs/Cox-2 inhibitors was not related to any clinically significant increase in adverse events. FEBUXOSTAT can be co-administered with naproxen with no dose adjustment of FEBUXOSTAT or naproxen being necessary.
Inducers of glucuronidation: Potent inducers of UGT enzymes might possibly lead to increased metabolism and decreased efficacy of FEBUXOSTAT. Monitoring of serum uric acid is therefore recommended 1-2 weeks after start of treatment with a potent inducer of glucuronidation. Conversely, cessation of treatment of an inducer might lead to increased plasma levels of FEBUXOSTAT.
Colchicine/Indomethacin/Hydrochlorothiazide/Warfarin: FEBUXOSTAT can be co-administered with colchicine or indomethacin with no dose adjustment of FEBUXOSTAT or the co-administered active substance being necessary.
No dose adjustment is necessary for FEBUXOSTAT when administered with hydrochlorothiazide. No dose adjustment is necessary for warfarin when administered with FEBUXOSTAT. After initiation of FEBUXOSTAT therapy, monitoring of anticoagulant activity should be considered in patients receiving warfarin or similar agents.
Desipramine/CYP2D6 substrates: FEBUXOSTAT was shown to be a weak inhibitor of CYP2D6 in vitro. In a study in healthy subjects, 120 mg FEBUXOSTAT resulted in a mean 22% increase in AUC of desipramine, a CYP2D6 substrate indicating a potential weak inhibitory effect of FEBUXOSTAT on the CYP2D6 enzyme in vivo. Thus, co-administration of FEBUXOSTAT with other CYP2D6 substrates is not expected to require any dose adjustment for those compounds.
Antacids: Concomitant ingestion of an antacid containing magnesium hydroxide and aluminum hydroxide has been shown to delay absorption of FEBUXOSTAT (approximately 1 hour) and to cause a 32% decrease in C_max, but no significant change in AUC was observed. Therefore, FEBUXOSTAT may be taken without regard to antacid use.