Xozid Drug Interactions

Xanthine Oxidase Substrate Drugs-Azathioprine, Mercaptopurine and Theophylline: Inhibition of XO by febuxostat may cause increased plasma concentrations of these drugs leading to toxicity.
Febuxostat are contraindicated in patients being treated with azathioprine or mercaptopurine.
Azathioprine and mercaptopurine undergo metabolism via three major metabolic pathways, one of which is mediated by XO. Concomitant administration of allopurinol [a xanthine oxidase inhibitor] with azathioprine or mercaptopurine has been reported to substantially increase plasma concentrations of these drugs. Because febuxostat is a xanthine oxidase inhibitor, it could inhibit the XO-mediated metabolism of azathioprine and mercaptopurine leading to increased plasma concentrations of azathioprine or mercaptopurine that could result in severe toxicity.
Theophylline: No dose adjustment is necessary for theophylline when co-administered with febuxostat. The study demonstrated an approximately 400-fold increase in the amount of 1-¬methylxanthine (one of the major theophylline metabolites) excreted in urine as a result of XO inhibition by febuxostat. The safety of long-term exposure to 1-methylxanthine has not been evaluated. This should be taken into consideration when deciding to co-administer febuxostat tablets and theophylline.
P450 Substrate Drugs: In vitro studies have shown that febuxostat does not inhibit P450 enzymes CYP1A2, 2C9, 2C19, 2D6, or 3A4 and it also does not induce CYP1A2, 2B6, 2C9, 2C19, or 3A4 at clinically relevant concentrations. Pharmacokinetic interactions between febuxostat and drugs metabolized by these CYP enzymes are unlikely.
Colchicine: No dose adjustment is necessary for either febuxostat or colchicine when the two drugs are co-administered.
Naproxen: No dose adjustment is necessary for febuxostat or naproxen when the two drugs are co-administered.
Indomethacin: No dose adjustment is necessary for either febuxostat or indomethacin when these two drugs are co-administered.
Hydrochlorothiazide: No dose adjustment is necessary for febuxostat when co-administered with hydrochlorothiazide.
Warfarin: No dose adjustment is necessary for warfarin when co-administered with febuxostat.
Desipramine: Co-administration of desipramine (CYP2D6 substrate) with febuxostat are not expected to require dose adjustment. Febuxostat was shown to be a weak inhibitor of CYP2D6 in vitro and in vivo.