{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T10:29:33Z","timestamp":1785925773172,"version":"3.56.0"},"reference-count":103,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2018,5,25]],"date-time":"2018-05-25T00:00:00Z","timestamp":1527206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The paper addresses the safety of febuxostat and summarizes reports on side effects and interactions of febuxostat published by the cut-off date (last day of literature search) of 20 March 2018. Publications on side effects and the interactions of febuxostat were considered. Information concerning the occurrence of side effects and interactions in association with the treatment with febuxostat was collected and summarized in the review. The incidence of severe side effects was much less frequent than mild side effects (1.2\u20133.8% to 20.1\u201338.7%). The rate and range of febuxostat side effects are low at doses of up to 120 mg and only increase with a daily dose of over 120 mg. The publications reveal no age-dependent increase in side effects for febuxostat. In patients with impaired renal function, no increase in adverse events is described with a dose of up to 120 mg of febuxostat per day. Patients with impaired liver function had no elevated risk for severe side effects. A known allopurinol intolerance increases the risk of skin reactions during treatment with febuxostat by a factor of 3.6. No correlation between treatment with febuxostat and agranulocytosis has been confirmed. Possible interactions with very few medications (principally azathioprine) are known for febuxostat. Febuxostat is well tolerated and a modern and safe alternative to allopurinol therapy.<\/jats:p>","DOI":"10.3390\/ph11020051","type":"journal-article","created":{"date-parts":[[2018,5,28]],"date-time":"2018-05-28T03:54:21Z","timestamp":1527479661000},"page":"51","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["Side Effects and Interactions of the Xanthine Oxidase Inhibitor Febuxostat"],"prefix":"10.3390","volume":"11","author":[{"given":"Andreas","family":"Jordan","sequence":"first","affiliation":[{"name":"Internal Medicine, Medical Faculty, Ludwig Maximilians University of Munich, 80539 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Gresser","sequence":"additional","affiliation":[{"name":"Internal Medicine, Medical Faculty, Ludwig Maximilians University of Munich, 80539 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,5,25]]},"reference":[{"key":"ref_1","first-page":"549","article-title":"Gout\u2014Current diagnosis and treatment","volume":"106","author":"Tausche","year":"2009","journal-title":"Deutsches \u00c4rzteblatt Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"123105","DOI":"10.1155\/2014\/123105","article-title":"Urate lowering therapy with febuxostat in daily practice\u2014A multicentre, open-label, prospective observational study","volume":"2014","author":"Tausche","year":"2014","journal-title":"Int. J. Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"ii15","DOI":"10.1093\/rheumatology\/kep088","article-title":"Febuxostat: A new treatment for hyperuricaemia in gout","volume":"48","author":"Edwards","year":"2009","journal-title":"Rheumatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1161\/01.CIR.0000056762.69302.46","article-title":"Electron spin resonance characterization of vascular xanthine and NAD(P)H oxidase activity in patients with coronary artery disease: Relation to endothelium-dependent vasodilation","volume":"107","author":"Spiekermann","year":"2003","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8745","DOI":"10.1073\/pnas.93.16.8745","article-title":"Circulating plasma xanthine oxidase contributes to vascular dysfunction in hypercholesterolemic rabbits","volume":"93","author":"White","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1161\/01.HYP.30.1.57","article-title":"Xanthine oxidase inhibition with oxypurinol improves endothelial vasodilator function in hypercholesterolemic but not in hypertensive patients","volume":"30","author":"Cardillo","year":"1997","journal-title":"Hypertension"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s00296-013-2857-2","article-title":"As compared to allopurinol, urate-lowering therapy with febuxostat has superior effects on oxidative stress and pulse wave velocity in patients with severe chronic tophaceous gout","volume":"34","author":"Tausche","year":"2014","journal-title":"Rheumatol. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1056\/NEJMoa050373","article-title":"Febuxostat compared with allopurinol in patients with hyperuricemia and gout","volume":"353","author":"Becker","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1002\/art.24209","article-title":"Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: A 28-week, phase III, randomized, double-blind, parallel-group trial","volume":"59","author":"Schumacher","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1093\/rheumatology\/ken457","article-title":"Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study","volume":"48","author":"Schumacher","year":"2009","journal-title":"Rheumatology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"R63","DOI":"10.1186\/ar2978","article-title":"The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: The CONFIRMS trial","volume":"12","author":"Becker","year":"2010","journal-title":"Arthritis Res. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/j.1365-2125.2010.03667.x","article-title":"Effect of hydrochlorothiazide on the pharmacokinetics and pharmacodynamics of febuxostat, a non-purine selective inhibitor of xanthine oxidase","volume":"70","author":"Grabowski","year":"2010","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.1097\/RHU.0b013e31821d36cc","article-title":"Placebo-controlled, double-blind study of the non-purine-selective xanthine oxidase inhibitor Febuxostat (TMX-67) in patients with hyperuricemia including those with gout in Japan: Phase 3 clinical study","volume":"17","author":"Kamatani","year":"2011","journal-title":"J. Clin. Rheumatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1038\/hr.2014.107","article-title":"Safety, efficacy and renal effect of febuxostat in patients with moderate-to-severe kidney dysfunction","volume":"37","author":"Shibagaki","year":"2014","journal-title":"Hypertens. Res. Off. J. Jpn. Soc. Hypertens."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1002\/art.39654","article-title":"Impact of febuxostat on renal function in gout patients with moderate-to-severe renal impairment","volume":"68","author":"Saag","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"White, W.B., Saag, K.G., Becker, M.A., Borer, J.S., Gorelick, P.B., Whelton, A., Hunt, B., and Castillo, M. (2018). Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout. N. Engl. J. Med.","DOI":"10.1056\/NEJMoa1710895"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1097\/RHU.0b013e31821d36f2","article-title":"A repeated oral administration study of febuxostat (TMX-67), a non-purine-selective inhibitor of xanthine oxidase, in patients with impaired renal function in Japan: Pharmacokinetic and pharmacodynamic study","volume":"17","author":"Hosoya","year":"2011","journal-title":"J. Clin. Rheumatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1177\/0091270010365549","article-title":"Metabolism and excretion of 14C febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, in healthy male subjects","volume":"51","author":"Grabowski","year":"2011","journal-title":"J. Clin. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"393","DOI":"10.3892\/etm.2013.1414","article-title":"Pharmacokinetics and pharmacodynamics of febuxostat under fasting conditions in healthy individuals","volume":"7","author":"Zhang","year":"2014","journal-title":"Exp. Ther. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1111\/j.1365-2125.2007.03016.x","article-title":"Effect of food or antacid on pharmacokinetics and pharmacodynamics of febuxostat in healthy subjects","volume":"65","author":"Khosravan","year":"2008","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1177\/0091270008322035","article-title":"The effect of age and gender on pharmacokinetics, pharmacodynamics, and safety of febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase","volume":"48","author":"Khosravan","year":"2008","journal-title":"J. Clin. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1097\/00045391-200501000-00005","article-title":"Pharmacokinetics and pharmacodynamics of febuxostat, a new non-purine selective inhibitor of xanthine oxidase in subjects with renal impairment","volume":"12","author":"Mayer","year":"2005","journal-title":"Am. J. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1081\/NCN-200027377","article-title":"PK\/PD and safety of a single dose of TMX-67 (febuxostat) in subjects with mild and moderate renal impairment","volume":"23","author":"Hoshide","year":"2004","journal-title":"Nucleosides Nucleotides Nucleic Acids"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"331","DOI":"10.5414\/CP201648","article-title":"The effects of xanthine oxidase inhibition by febuxostat on the pharmacokinetics of theophylline","volume":"50","author":"Tsai","year":"2012","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1111\/j.1365-2125.2012.04182.x","article-title":"The effects of febuxostat on the pharmacokinetic parameters of rosiglitazone, a CYP2C8 substrate","volume":"74","author":"Naik","year":"2012","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1081\/NCN-200027372","article-title":"Febuxostat (TMX-67), a novel, non-purine, selective inhibitor of xanthine oxidase, is safe and decreases serum urate in healthy volunteers","volume":"23","author":"Becker","year":"2004","journal-title":"Nucleosides Nucleotides Nucleic Acids"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"433","DOI":"10.3109\/10641963.2013.846358","article-title":"Febuxostat (Feburic tablet) in the management of hyperuricemia in a general practice cohort of Japanese patients with a high prevalence of cardiovascular problems","volume":"36","author":"Hiramitsu","year":"2014","journal-title":"Clin. Exp. Hypertens."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.jbspin.2015.07.011","article-title":"Risk of cutaneous adverse events with febuxostat treatment in patients with skin reaction to allopurinol. A retrospective, hospital-based study of 101 patients with consecutive allopurinol and febuxostat treatment","volume":"83","author":"Bardin","year":"2016","journal-title":"Jt. Bone Spine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1159\/000434633","article-title":"Population pharmacokinetics and therapeutic efficacy of febuxostat in patients with severe renal impairment","volume":"96","author":"Hira","year":"2015","journal-title":"Pharmacology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"779","DOI":"10.3109\/14397595.2015.1016257","article-title":"Effects of febuxostat on serum urate level in Japanese hyperuricemia patients","volume":"25","author":"Yamamoto","year":"2015","journal-title":"Mod. Rheumatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"304","DOI":"10.3109\/03009742.2015.1099729","article-title":"Safety and efficacy of oral febuxostat for treatment of HLA-B*5801-negative gout: A randomized, open-label, multicentre, allopurinol-controlled study","volume":"45","author":"Yu","year":"2016","journal-title":"Scand. J. Rheumatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.3899\/jrheum.110092","article-title":"Safety and efficacy of febuxostat treatment in subjects with gout and severe allopurinol adverse reactions","volume":"38","author":"Chohan","year":"2011","journal-title":"J. Rheumatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.2147\/CIA.S70855","article-title":"Efficacy and safety of febuxostat in elderly female patients","volume":"9","author":"Mizuno","year":"2014","journal-title":"Clin. Interv. Aging"},{"key":"ref_34","first-page":"A776","article-title":"The effectiveness and safety of febuxostat: An experience in medical center in Taiwan","volume":"17","author":"Wang","year":"2014","journal-title":"Value Health"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1111\/1756-185X.12648","article-title":"A phase 3, multicenter, randomized, allopurinol-controlled study assessing the safety and efficacy of oral febuxostat in Chinese gout patients with hyperuricemia","volume":"18","author":"Xu","year":"2015","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.2215\/CJN.01760213","article-title":"Randomized controlled trial of febuxostat versus allopurinol or placebo in individuals with higher urinary uric acid excretion and calcium stones","volume":"8","author":"Goldfarb","year":"2013","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"39","DOI":"10.4137\/DTI.S16524","article-title":"Febuxostat for hyperuricemia in patients with advanced chronic kidney disease","volume":"8","author":"Akimoto","year":"2014","journal-title":"Drug Target Insights"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1053\/j.ajkd.2015.05.017","article-title":"Efficacy of febuxostat for slowing the GFR decline in patients with CKD and asymptomatic hyperuricemia: A 6-month, double-blind, randomized, placebo-controlled trial","volume":"66","author":"Sircar","year":"2015","journal-title":"Am. J. Kidney Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3247","DOI":"10.2169\/internalmedicine.55.6791","article-title":"Comparison of the renoprotective effect of febuxostat for the treatment of hyperuricemia between patients with and without type 2 diabetes mellitus: A retrospective observational study","volume":"55","author":"Ito","year":"2016","journal-title":"Intern. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1002\/art.39769","article-title":"Febuxostat for patients with gout and severe chronic kidney disease: Which is the appropriate dosage? Comment on the article by Saag et al.","volume":"68","author":"Quilis","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1111\/1756-185X.12266","article-title":"An allopurinol-controlled, multicenter, randomized, double-blind, parallel between-group, comparative study of febuxostat in Chinese patients with gout and hyperuricemia","volume":"17","author":"Huang","year":"2014","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.transproceed.2013.09.045","article-title":"Efficacy and safety of febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase for the treatment of hyperuricemia in kidney transplant recipients","volume":"46","author":"Tojimbara","year":"2014","journal-title":"Transplant. Proc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"245","DOI":"10.2147\/DDDT.S56597","article-title":"Efficacy and safety of febuxostat in the treatment of hyperuricemia in stable kidney transplant recipients","volume":"8","author":"Sofue","year":"2014","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1053\/j.ajkd.2016.07.001","article-title":"Febuxostat in hyperuricemic patients with advanced CKD","volume":"68","author":"Lim","year":"2016","journal-title":"Am. J. Kidney Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"S44","DOI":"10.1097\/RHU.0b013e31821d36cc","article-title":"An allopurinol-controlled, multicenter, randomized, open-label, parallel between-group, comparative study of febuxostat (TMX-67), a non-purine-selective inhibitor of xanthine oxidase, in patients with hyperuricemia including those with gout in Japan: Phase 2 exploratory clinical study","volume":"17","author":"Kamatani","year":"2011","journal-title":"J. Clin. Rheumatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1097\/RHU.0b013e31821d36cc","article-title":"An allopurinol-controlled, randomized, double-dummy, double-blind, parallel between-group, comparative study of febuxostat (TMX-67), a non-purine-selective inhibitor of xanthine oxidase, in patients with hyperuricemia including those with gout in Japan: Phase 3 clinical study","volume":"17","author":"Kamatani","year":"2011","journal-title":"J. Clin. Rheumatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"S50","DOI":"10.1097\/RHU.0b013e31822541d0","article-title":"Multicenter, open-label study of long-term administration of febuxostat (TMX-67) in Japanese patients with hyperuricemia including gout","volume":"17","author":"Kamatani","year":"2011","journal-title":"J. Clin. Rheumatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"S35","DOI":"10.1097\/RHU.0b013e31821d36cc","article-title":"Placebo-controlled double-blind dose-response study of the non-purine-selective xanthine oxidase inhibitor febuxostat (TMX-67) in patients with hyperuricemia (including gout patients) in japan: Late phase 2 clinical study","volume":"17","author":"Kamatani","year":"2011","journal-title":"J. Clin. Rheumatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1002\/art.20935","article-title":"Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase: A twenty-eight-day, multicenter, phase II, randomized, double-blind, placebo-controlled, dose-response clinical trial examining safety and efficacy in patients with gout","volume":"52","author":"Becker","year":"2005","journal-title":"Arthritis Rheum."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1177\/0091270005282634","article-title":"The effect of mild and moderate hepatic impairment on pharmacokinetics, pharmacodynamics, and safety of febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase","volume":"46","author":"Khosravan","year":"2006","journal-title":"J. Clin. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"821","DOI":"10.2165\/00003088-200645080-00005","article-title":"Pharmacokinetics, pharmacodynamics and safety of febuxostat, a non-purine selective inhibitor of xanthine oxidase, in a dose escalation study in healthy subjects","volume":"45","author":"Khosravan","year":"2006","journal-title":"Clin. Pharmacokinet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1177\/0091270006289848","article-title":"Pharmacokinetic interactions of concomitant administration of febuxostat and NSAIDs","volume":"46","author":"Khosravan","year":"2006","journal-title":"J. Clin. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1186\/2193-1801-3-501","article-title":"Hypouricemic effect and safety of febuxostat used for prevention of tumor lysis syndrome","volume":"3","author":"Maie","year":"2014","journal-title":"SpringerPlus"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.3899\/jrheum.080814","article-title":"Clinical efficacy and safety of successful longterm urate lowering with febuxostat or allopurinol in subjects with gout","volume":"36","author":"Becker","year":"2009","journal-title":"J. Rheumatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e13","DOI":"10.1097\/TP.0b013e3182247b45","article-title":"Gout and transplantation: New treatment option\u2013Same old drug interaction","volume":"92","author":"Kaczmorski","year":"2011","journal-title":"Transplantation"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1111\/dom.12135","article-title":"Diabetes and gout: Efficacy and safety of febuxostat and allopurinol","volume":"15","author":"Becker","year":"2013","journal-title":"Diabetes Obes. Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1080\/15257770.2011.603715","article-title":"Treating hyperuricemia of gout: Safety and efficacy of febuxostat and allopurinol in older versus younger subjects","volume":"30","author":"Becker","year":"2011","journal-title":"Nucleosides Nucleotides Nucleic Acids"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1093\/rheumatology\/ket487","article-title":"Pharmacodynamic, pharmacokinetic and tolerability evaluation of concomitant administration of lesinurad and febuxostat in gout patients with hyperuricaemia","volume":"53","author":"Fleischmann","year":"2014","journal-title":"Rheumatology"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Steinberg, A.S., Vince, B.D., Choi, Y.-J., Martin, R.L., McWherter, C.A., and Boudes, P.F. (2016). The pharmacodynamics, pharmacokinetics, and safety of arhalofenate in combination with febuxostat when treating hyperuricemia associated with gout. J. Rheumatol.","DOI":"10.3899\/jrheum.161062"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1177\/1060028014521389","article-title":"Febuxostat as a novel option to optimize thiopurines\u2019 metabolism in patients with inadequate metabolite levels","volume":"48","author":"Dore","year":"2014","journal-title":"Ann. Pharmacother."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"659","DOI":"10.3899\/jrheum.111161","article-title":"Febuxostat hypersensitivity","volume":"39","author":"Abeles","year":"2012","journal-title":"J. Rheumatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"182","DOI":"10.4103\/0378-6323.129420","article-title":"Interstitial granulomatous drug reaction due to febuxostat","volume":"80","author":"Laura","year":"2014","journal-title":"Indian J. Dermatol. Venereol. Leprol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1684\/ejd.2016.2796","article-title":"Fixed drug eruption-like macules caused by febuxostat","volume":"26","author":"Oda","year":"2016","journal-title":"Eur. J. Dermatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1111\/jcpt.12322","article-title":"Febuxostat-associated drug reaction with eosinophilia and systemic symptoms (DRESS)","volume":"40","author":"Chou","year":"2015","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_65","first-page":"251","article-title":"Febuxostat hypersensitivity: Another cause of DRESS syndrome in chronic kidney disease?","volume":"48","author":"Paschou","year":"2016","journal-title":"Eur. Ann. Allergy Clin. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e67","DOI":"10.1016\/j.amjmed.2016.08.042","article-title":"Cross-reactions between allopurinol and febuxostat","volume":"130","author":"Lien","year":"2017","journal-title":"Am. J. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1111\/jcpt.12144","article-title":"Rhabdomyolysis associated with initiation of febuxostat therapy for hyperuricaemia in a patient with chronic kidney disease","volume":"39","author":"Kang","year":"2014","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"107","DOI":"10.5694\/mja14.01404","article-title":"Febuxostat-associated rhabdomyolysis in chronic renal failure","volume":"203","author":"Ghosh","year":"2015","journal-title":"Med. J. Aust."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Chahine, G., Saleh, K., Ghorra, C., Khoury, N., Khalife, N., and Fayad, F. (2016). Febuxostat-associated eosinophilic polymyositis in marginal zone lymphoma. Jt. Bone Spine.","DOI":"10.1016\/j.jbspin.2016.10.008"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/jcpt.12057","article-title":"Acute neutropenia associated with initiation of febuxostat therapy for hyperuricaemia in patients with chronic kidney disease","volume":"38","author":"Kobayashi","year":"2013","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1093\/ckj\/sfs092","article-title":"ANCA-positive pauci-immune glomerulonephritis and febuxostat treatment","volume":"5","author":"Izzedine","year":"2012","journal-title":"Clin. Kidney J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1002\/hep.28403","article-title":"Febuxostat-induced acute liver injury","volume":"63","author":"Bohm","year":"2016","journal-title":"Hepatology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1007\/s00296-014-3189-6","article-title":"Safety of allopurinol compared with other urate-lowering drugs in patients with gout: A systematic review and meta-analysis","volume":"35","author":"Castrejon","year":"2015","journal-title":"Rheumatol. Int."},{"key":"ref_74","first-page":"CD006077","article-title":"Allopurinol for chronic gout","volume":"10","author":"Seth","year":"2014","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.semarthrit.2013.05.004","article-title":"A systematic review and meta-analysis on the safety and efficacy of febuxostat versus allopurinol in chronic gout","volume":"43","author":"Faruque","year":"2013","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Gunawardhana, L., McLean, L., Punzi, H.A., Hunt, B., Palmer, R.N., Whelton, A., and Feig, D.I. (2017). Effect of Febuxostat on Ambulatory Blood Pressure in Subjects With Hyperuricemia and Hypertension: A Phase 2 Randomized Placebo-Controlled Study. J. Am. Heart Assoc., 6.","DOI":"10.1161\/JAHA.117.006683"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"33082","DOI":"10.1038\/srep33082","article-title":"Comparative efficacy and safety of urate-lowering therapy for the treatment of hyperuricemia: A systematic review and network meta-analysis","volume":"6","author":"Li","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_78","first-page":"656","article-title":"Allopurinol-induced DRESS syndrome","volume":"7","author":"Markel","year":"2005","journal-title":"Isr. Med. Assoc. J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1111\/j.1525-139X.2007.00270.x","article-title":"Allopurinol dosing in renal impairment: Walking the tightrope between adequate urate lowering and adverse events","volume":"20","author":"Dalbeth","year":"2007","journal-title":"Semin. Dial."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"23","DOI":"10.2147\/VHRM.S115080","article-title":"An evidence-based review on urate-lowering treatments: Implications for optimal treatment of chronic hyperuricemia","volume":"13","author":"Bove","year":"2017","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_81","unstructured":"Baek, C.H., Kim, H., Yang, W.S., Han, D.J., and Park, S.-K. (2017). Efficacy and Safety of Febuxostat in Kidney Transplant Patients. Exp. Clin. Transplant."},{"key":"ref_82","unstructured":"Ratiopharm GmbH (2017, March 05). Fachinformation zu \u201cAllopurinol-ratiopharm 100\/300 mg Tabletten\u201d. Available online: http:\/\/www.ratiopharm.de\/index.php?eID=dumpFile&t=f&f=70732&g=-1&r=1894%2C1894&token=38cd525615b9b72e43152a6306fbb025793a5c41."},{"key":"ref_83","unstructured":"Berlin-Chemie, A.G. (2018, March 18). Fachinformation Adenuric. Available online: http:\/\/www.fachinfo.de\/pdf\/012335."},{"key":"ref_84","first-page":"35","article-title":"Pharmacology of drugs for hyperuricemia. Mechanisms, kinetics and interactions","volume":"147","author":"Pea","year":"2005","journal-title":"Contrib. Nephrol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1177\/1759720X16682010","article-title":"Use of febuxostat in the management of gout in the United Kingdom","volume":"9","author":"Waller","year":"2017","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s11926-009-0019-z","article-title":"A critical reappraisal of allopurinol dosing, safety, and efficacy for hyperuricemia in gout","volume":"11","author":"Chao","year":"2009","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1136\/annrheumdis-2015-207919","article-title":"Lesinurad in combination with allopurinol: Results of a phase 2, randomised, double-blind study in patients with gout with an inadequate response to allopurinol","volume":"75","author":"Sundy","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Bardin, T., Keenan, R.T., Khanna, P.P., Kopicko, J., Fung, M., Bhakta, N., Adler, S., Storgard, C., Baumgartner, S., and So, A. (2016). Lesinurad in combination with allopurinol: A randomised, double-blind, placebo-controlled study in patients with gout with inadequate response to standard of care (the multinational CLEAR 2 study). Ann. Rheum. Dis.","DOI":"10.1136\/annrheumdis-2016-209213"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"591","DOI":"10.2165\/11592750-000000000-00000","article-title":"The challenges of gout management in the elderly","volume":"28","author":"Stamp","year":"2011","journal-title":"Drugs Aging"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1111\/j.1440-1746.2010.06254.x","article-title":"Azathioprine and allopurinol: A two-edged interaction","volume":"25","author":"Gearry","year":"2010","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1097\/00002826-200209000-00008","article-title":"Colchicine-induced acute myopathy in a patient with concomitant use of simvastatin","volume":"25","author":"Hsu","year":"2002","journal-title":"Clin. Neuropharmacol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1002\/mus.20135","article-title":"Cytoskeletal myotoxicity from simvastatin and colchicine","volume":"30","author":"Baker","year":"2004","journal-title":"Muscle Nerve"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1345\/aph.1E593","article-title":"Acute myopathy in a patient with concomitant use of pravastatin and colchicine","volume":"39","author":"Alayli","year":"2005","journal-title":"Ann. Pharmacother."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1345\/aph.1E653","article-title":"Possible colchicine rhabdomyolysis in a fluvastatin-treated patient","volume":"39","author":"Atasoyu","year":"2005","journal-title":"Ann. Pharmacother."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1345\/aph.1H064","article-title":"Rhabdomyolysis in a patient treated with colchicine and atorvastatin","volume":"40","author":"Tufan","year":"2006","journal-title":"Ann. Pharmacother."},{"key":"ref_96","first-page":"147","article-title":"Rhabdomyolysis induced by co-administration of fluvastatin and colchicine","volume":"74","author":"Sarullo","year":"2010","journal-title":"Monaldi Arch. Chest Dis."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.semarthrit.2015.06.013","article-title":"Colchicine\u2014Update on mechanisms of action and therapeutic uses","volume":"45","author":"Leung","year":"2015","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"744","DOI":"10.2215\/CJN.08280816","article-title":"Risk of Febuxostat-Associated Myopathy in Patients with CKD","volume":"12","author":"Liu","year":"2017","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1002\/art.1780290111","article-title":"The allopurinol hypersensitivity syndrome. Unnecessary morbidity and mortality","volume":"29","author":"Singer","year":"1986","journal-title":"Arthritis Rheum."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/RHU.0b013e318204aab4","article-title":"Renal function in gout: Long-term treatment effects of febuxostat","volume":"17","author":"Whelton","year":"2011","journal-title":"J. Clin. Rheumatol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1002\/acr.20680","article-title":"Women with gout: Efficacy and safety of urate-lowering with febuxostat and allopurinol","volume":"64","author":"Chohan","year":"2012","journal-title":"Arthritis Care Res. (Hoboken)"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Jackson, R.L., Hunt, B., and MacDonald, P.A. (2012). The efficacy and safety of febuxostat for urate lowering in gout patients >= 65 years of age. BMC Geriatr., 12.","DOI":"10.1186\/1471-2318-12-11"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Wells, A.F., MacDonald, P.A., Chefo, S., and Jackson, R.L. (2012). African American patients with gout: Efficacy and safety of febuxostat vs allopurinol. BMC Musculoskelet. Disord., 13.","DOI":"10.1186\/1471-2474-13-15"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/11\/2\/51\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:05:57Z","timestamp":1760195157000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/11\/2\/51"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,25]]},"references-count":103,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2018,6]]}},"alternative-id":["ph11020051"],"URL":"https:\/\/doi.org\/10.3390\/ph11020051","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,25]]}}}