Efficacy and safety of febuxostat in patients with hyperuricemia and gout

Abstract

The past decade has witnessed an exponential increase of novel therapeutic modalities for a variety of rheumatic disorders, including gout. During the past few years two novel therapeutic agents have been approved by the US Food and Drug Administration for the treatment of hyperuricemia in patients with gout, one of them being febuxostat, a nonpurine selective inhibitor of xanthine oxidase. Review of its pharmacokinetics and pharmacodynamics, efficacy and safety profile, and use in gout patients with comorbid conditions reveals that age and gender have no clinically significant effect and dose adjustments based on age or gender are not required. In addition, febuxostat can be used in patients with mild-to-moderate renal or hepatic involvement. Its overall efficacy and safety profile is comparable and, in certain subsets such as gout patients with mild and moderate renal insufficiency, is superior to allopurinol.

HLA-B*58:01is a risk factor for allopurinol-induced DRESS and Stevens-Johnson syndrome/toxic epidermal necrolysis in a Portuguese population

“…Moreover, the high prevalence of HLA-B*58:01 in allopurinol-tolerant controls in populations with a high prevalence of this allele, might unnecessarily limit the use of this cheap drug, and replace it with other xanthine oxidase inhibitors (febuxostat) or other uric acid-lowering agents, which may be less efficacious, more expensive or with fewer long-term safety studies. 1,48,49 However, pregenotyping in populations with a high prevalence of HLA-B*58:01 may prevent a significant number of severe, even fatal cases. One may question the cost-effectiveness of its regular use in populations with a prevalence of HLA-B*58:01 below 2%, such as ours.…”

Desensitization to febuxostat: report of two cases

“…7 Premarketing clinical trials estimated an incidence of 0.5% and 1.6% of cutaneous rash in patients treated with febuxostat 40 mg and 80 mg daily, respectively. 8 From 2009 to November 2012, the FDA received spontaneous reports of febuxostat hypersensitivity reactions, with a few cases of severe reactions such as SJS and anaphylactic shock, generally occurring within the first month of treatment. 9 Postmarketing surveillance studies estimate the frequency of SJS to be equal to or greater than 1/ 10,000 to less than 1/1,000.…”

Urolithiasis: An Update on Diagnostic Modalities and Treatment Protocols

“…Chemolytic dissolution therapy can be used as an adjunct to ESWL and PCNL, or can also be used to completely avoid surgery [86] . Commonly used synthetic drugs are listed in Table 1 [87][88][89][90][91][92][93][94] . Stones that are large in size or possess staghorn contours or are very proximal in location and also are unresponsive to medical therapy require surgical intervention or more correctly, active stone removal [95] .…”

“…Ureteroscopy is a minimally invasive technique that utilizes a flexible fiberoptic ureteroscope that passes through urethra via bladder up to the ureter for accessing [61,62,64,67] (hydrochlorothiazide, trichlormethiazide, chlorthalidone, indapamide) Calcium oxalate, calcium phosphate stones Potassium phosphate [66,87] Calcium oxalate stones Sodium cellulose phosphate [71,72] Calcium oxalate stones Allopurinol [65,82] Uric acid stones D-penicillamine [66,73,88] Cystine stones Febuxostat [89][90][91] Uric acid stones Potassium citrate [68,71] Calcium oxalate, uric acid stones Alpha blockers (tamsulosin, terazosin, doxazosin) [66,92] Ureteral stones Alpha mercaptopropionylglycine [66,88] Cystine stones Acetohydroxamic acid [66,71] Struvite stones Calcium channel blockers (nifedipine) [55] Ureteral stones Acetazolamide [21] Uric acid, cystine stones Sodium bicarbonate [66,93] Uric acid stones NSAIDs (diclofenac, indomethacin, ketorolac, ibuprofen) [19,94] All stone types the entire renal collecting system [96,[100][101][102] . It is equipped for extracting smaller stones as well as fragmenting larger ones using ballistic and laser (holmium: yttrium-aluminium-garnet laser/holmium: YAG laser) lithotripsy [17,96,101] due to which it has become a popular modality for treatment of urolithiasis in children and getting wider acceptance in pregnant women as well as in patients after urinary diversion …”