Acute neutropenia associated with initiation of febuxostat therapy for hyperuricaemia in patients with chronic kidney disease

Kobayashi, Susumu; Ogura, Makoto; Hosoya, Tatsuo

doi:10.1111/jcpt.12057

Cited by 20 publications

(16 citation statements)

References 18 publications

(17 reference statements)

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“…There was no evidence of liver dysfunction or hematologic abnormalities, although there is one report in the literature of acute neutropenia associated with febuxostat in a case of CKD. 11 There are several reasons why febuxostat is safer than other urate-lowering drugs such as allopurinol or probenecid in patients with CKD. Febuxostat is (1) primarily metabolized in the liver, (2) excreted in both the urine and feces, (3) highly selective in its mechanism of action and (4) not uricosuric (less likely to cause urolithiasis).…”

Section: Discussionmentioning

confidence: 99%

Safety, efficacy and renal effect of febuxostat in patients with moderate-to-severe kidney dysfunction

et al. 2014

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Hyperuricemia (HU) is common in patients with chronic kidney disease (CKD), and accumulating evidence suggests it has a pathogenic role in the progression of the disease. However, a major challenge in treating patients with HU is the adverse effects caused by urate-lowering drugs used to treat CKD. Because of these untoward effects, doses need to be reduced, which leads to suboptimal efficacy. Febuxostat has been shown to be highly efficacious in reducing serum uric acid (sUA) and is well tolerated in patients with mild kidney dysfunction. However, its safety and efficacy have not been well studied in more advanced cases of CKD. We studied the safety and efficacy of escalating doses of febuxostat over a 24-week period in 70 patients with CKD stages 3b, 4 and 5, and we also observed the changes in blood pressure, estimated glomerular filtration rate (eGFR) and proteinuria following the reduction of sUA. Drug-related adverse events (AEs) occurred in only 5 out of 70 patients. All but one of the events were mild, and all five patients fully recovered. By 24 weeks, the reduction of sUA levels was >40% in CKD stage 3b and >50% in CKD stages 4 and 5. More than 70% of patients achieved target sUA levels of 6 mg dl(-1) or less. Multivariate analysis showed that a greater reduction in sUA with febuxostat was associated with an increase in eGFR and a tendency toward decreased proteinuria. Febuxostat was safe and efficacious in the treatment of CKD stages 3b-5.

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Section: Discussionmentioning

confidence: 99%

Safety, efficacy and renal effect of febuxostat in patients with moderate-to-severe kidney dysfunction

et al. 2014

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“…In these 2 patients, neutrophil count increased within 5 to 7 days after febuxostat discontinuation and with G-CSF support. [15] Apparently, our patient had more advanced renal disease and exposed to higher dose of febuxostat for longer duration (40 mg qd for 2.5 months), and then had lower neutropenic nadir and exhibited longer neutropenic period of time. Table 1 shows comparison of clinical presentation of reported cases of febuxostat-induced agranulocytosis.…”

Section: Discussionmentioning

confidence: 89%

“…[15] A 74-year-old woman with liver cirrhosis and CKD stage 3 was treated with febuxostat 10 mg per day for hyperuricemia during hospitalization. Eleven days after febuxostat administration, she developed neutropenia with absolute neutrophil count only 600/μL.…”

Section: Discussionmentioning

confidence: 99%

Febuxostat-induced agranulocytosis in an end-stage renal disease patient

2017

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Introduction:Febuxostat, a nonpurine xanthine oxidase inhibitor, is approved as the first-line urate-lowering therapy in gout patients with normal renal function or mild to moderate renal impairment. The most common adverse effects of febuxostat are liver function test abnormalities, diarrhea, and skin rash. However, there is insufficient data in patients with severe renal impairment and end-stage renal disease (ESRD). We report the first case, to our knowledge, in which agranulocytosis developed after febuxostat treatment in an ESRD patient.Clinical presentation:A 67-year-old woman with gout and ESRD received febuxostat 40 mg a day for 2.5 months. She subsequently complicated with febrile neutropenia and the absolute neutrophil count was only 14/μL. After broad-spectrum antibiotics treatment and no more exposure to febuxostat for 17 days, her infection and neutrophil count recovered. Bone marrow study during neutropenic period showed myeloid hypoplasia without evidence of hematologic neoplasms.Conclusion:As febuxostat use may become more common in the population of advanced renal failure, clinicians should be aware of this rare but potentially life-threatening adverse effect. Based on our experience, close monitoring hemogram and immediate discontinuation of this medication may prevent serious consequences.

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“…AEs of febuxostat were defined as more than twofold increases in Common Terminology Criteria for Adverse Events scores compared with baseline. We focused on AEs commonly observed at high frequency when using xanthine oxidase inhibitors 6–8,17. Among them, leukopenia hepatic disorder, thrombocytopenia, and anemia were selected for use as secondary end points in the present study.…”

Section: Methodsmentioning

confidence: 99%

Efficacy and safety of febuxostat in elderly female patients

Mizuno¹,

Hayashi²,

Hikosaka³

et al. 2014

CIA

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BackgroundMaintenance of low serum urate levels is important for the management of gout. Achieving the recommended serum urate levels of less than 6.0 mg/dL is difficult in elderly (65 years of age or older) patients with renal impairment. Xanthine oxidase inhibitors allopurinol and febuxostat are used for this purpose. Although febuxostat had been shown to be efficacious in elderly patients, its safety and efficacy in elderly female patients with hyperuricemia remain unclear.ObjectiveThe aim of this study was to assess the efficacy and safety of febuxostat in elderly female patients.MethodsWe studied a retrospective cohort study. The study included elderly Japanese patients (65 years of age or older) who were treated with febuxostat at Fujita Health University Hospital from January 2012 to December 2013. The treatment goal was defined as achievement of serum urate levels of 6.0 mg/dL or lower within 16 weeks; this was the primary endpoint in the present study. Adverse events of febuxostat were defined as more than twofold increases in Common Terminology Criteria for adverse events scores from baseline.ResultsWe evaluated 82 patients treated with febuxostat during the observation period and classified them into male (n=53) and female (n=29) groups. The mean time to achievement of the treatment goal was significantly shorter in the female group (53 days) than in the male group (71 days). There were no significant differences in adverse events between the 2 groups.ConclusionOur findings suggest that the efficacy of febuxostat in elderly female patients is superior to that in elderly male patients and that the safety is equivalent.

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Acute neutropenia associated with initiation of febuxostat therapy for hyperuricaemia in patients with chronic kidney disease

Cited by 20 publications

References 18 publications

Safety, efficacy and renal effect of febuxostat in patients with moderate-to-severe kidney dysfunction

Safety, efficacy and renal effect of febuxostat in patients with moderate-to-severe kidney dysfunction

Febuxostat-induced agranulocytosis in an end-stage renal disease patient

Efficacy and safety of febuxostat in elderly female patients

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