febuxostat (Uloric)
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Indications
- treatment of gout not responding to allopurinol*
- useful in patients with mild renal insufficiency
* has not been demonstrated to improve clinical outcomes[5] Contrandications: (caution)
- creatinine clearance < 30 mL/min
- hepatic disease, Child-Pugh class C
- use in combination with theophylline, mercaptopurine, or azathioprine
Dosage
- start 40 mg PO day
- increase to 80 mg/day after 2 weeks if serum uric acid > 6 mg/dL
- maximum 80 mg/day
Tabs: 40 mg, 80 mg
Dosage adjustment in renal failure
- none for mild to moderate renal insufficiency (CrCl >= 30 mL/min)
- febuxostat without effect on renal function in hyperuricemic patients with stage 3 chronic kidney disease*[10]
* CKD stage 3 = 30-60 mL/min/1.73 m2
Pharmacokinetics
- metabolized in the liver by both oxidation via cytochrome P450s CYP1A2, CYP2C8, & CYP2C9 & non-P450 enzymes & by conjugation via various uridine diphosphate glucuronosyltransferase
- eliminated by both liver & kidneys
Monitor
- baseline serum uric acid level, LFTs, & CBC
- recheck after 2 & 4 months, then periodically[4]
Adverse effects
- abnormal liver function tests (4-7%)
- nausea (1%)
- arthralgia (1%)
- rash (1-2%)
- frequent gout flares may occur when starting febuxostat
- chronic renal failure
- allopurinol is associated with less chronic renal failure than febuxostat[8]
- increased risk of cardiovascular events?[9] or not[12]
* Boxed warning: increased risk of death[11]
Drug interactions
- avoid use in combination with theophylline, mercaptopurine, or azathioprine; these drugs are metabolized by xanthine oxidase, thus may accumulate to toxic levels[6][7]
Mechanism of action
- xanthine oxidase inhibitor
Notes
Cost: ~$160/month (2009)
More general terms
References
- ↑ Prescriber's Letter 16(4): 2009 New Drug: Uloric (Febuxostat) Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=250143&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Bruce SP. Febuxostat: a selective xanthine oxidase inhibitor for the treatment of hyperuricemia and gout. Ann Pharmacother 2006;40:2187-94 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17132810
- ↑ Mayer MD et al Pharmacokinetics and pharmacodynamics of febuxostat, a new non-purine selective inhibitor of xanthine oxidase in subjects with renal impairment. Am J Ther 2005;12:22-34. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15662289
- ↑ 4.0 4.1 Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260704&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 5.0 5.1 Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016 - ↑ 6.0 6.1 Medical Knowledge Self Assessment Program (MKSAP) 17, 18. American College of Physicians, Philadelphia 2015, 2018.
- ↑ 7.0 7.1 Khanna D et al 2012 American College of Rheumatology guidelines for management of gout. Part 1: Systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia Arthritis Care & Research, 64(10):1431-1446, October 2012 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23024028 <Internet> http://onlinelibrary.wiley.com/doi/10.1002/acr.21772/abstract
- ↑ 8.0 8.1 Singh JA, Cleveland JD. Comparative effectiveness of allopurinol versus febuxostat for preventing incident renal disease in older adults: An analysis of Medicare claims data. Ann Rheum Dis 2017 Jun 5 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28584186
- ↑ 9.0 9.1 FDA Safety Alert. Nov 15, 2017 Febuxostat (Brand Name Uloric): Drug Safety Communication - FDA to Evaluate Increased Risk of Heart-related Death. https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm585281.htm
- ↑ 10.0 10.1 Kimura K, Hosoya T, Uchida S et al. Febuxostat therapy for patients with stage 3 CKD and asymptomatic hyperuricemia: A randomized trial. Am J Kidney Dis 2018 Dec; 72:798-810. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30177485 Free Article https://www.ajkd.org/article/S0272-6386(18)30834-5/fulltext
- ↑ 11.0 11.1 FDA Safety Alert. Feb 21, 2019 Uloric (febuxostat): Boxed Warning Added - Due to Increased Risk of Death with Gout Medicine. https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/UCM631824
DA Safety Announcement. Feb 21, 2019 FDA adds Boxed Warning for increased risk of death with gout medicine Uloric (febuxostat). https://www.fda.gov/Drugs/DrugSafety/ucm631182.htm - ↑ 12.0 12.1 Mackenzie IS et al. Long-term cardiovascular safety of febuxostat compared with allopurinol in patients with gout (FAST): A multicentre, prospective, randomised, open-label, non-inferiority trial. Lancet 2020 Nov 9; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33181081 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32234-0/fulltext
- ↑ HIGHLIGHTS OF PRESCRIBING INFORMATION ULORIC. ULORIC (febuxostat) tablets, for oral use https://general.takedapharm.com/ULORICPI