Optimizing Therapy With Allopurinol: Factors Limiting Hypouricemic Efficacy

Chung, Yewon; Stocker, Sophie L.; Graham, Garry G.; Day, Richard O.

doi:10.1097/maj.0b013e31815acb10

Cited by 20 publications

(10 citation statements)

References 31 publications

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“…In this study, there was no titration of allopurinol doses; subjects were assigned the standard daily dose of 300 mg unless they had moderate renal impairment. For this reason and due to the paucity of controlled data cited above [42], we are reluctant to speculate as to whether allopurinol dose escalation would have safely increased the proportion of subjects who achieved target sUA [42,45]. …”

Section: Discussionmentioning

confidence: 99%

The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial

et al. 2010

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IntroductionThe purpose of this study was to compare urate-lowering (UL) efficacy and safety of daily febuxostat and allopurinol in subjects with gout and serum urate (sUA) ≥ 8.0 mg/dL in a six-month trial.MethodsSubjects (n = 2,269) were randomized to febuxostat 40 mg or 80 mg, or allopurinol 300 mg (200 mg in moderate renal impairment). Endpoints included the proportion of all subjects with sUA <6.0 mg/dL and the proportion of subjects with mild/moderate renal impairment and sUA <6.0 mg/dL. Safety assessments included blinded adjudication of each cardiovascular (CV) adverse event (AE) and death.ResultsComorbidities included: renal impairment (65%); obesity (64%); hyperlipidemia (42%); and hypertension (53%). In febuxostat 40 mg, febuxostat 80 mg, and allopurinol groups, primary endpoint was achieved in 45%, 67%, and 42%, respectively. Febuxostat 40 mg UL was statistically non-inferior to allopurinol, but febuxostat 80 mg was superior to both (P < 0.001). Achievement of target sUA in subjects with renal impairment was also superior with febuxostat 80 mg (72%; P < 0.001) compared with febuxostat 40 mg (50%) or allopurinol (42%), but febuxostat 40 mg showed greater efficacy than allopurinol (P = 0.021). Rates of AEs did not differ across treatment groups. Adjudicated (APTC) CV event rates were 0.0% for febuxostat 40 mg and 0.4% for both febuxostat 80 mg and allopurinol. One death occurred in each febuxostat group and three in the allopurinol group.ConclusionsUrate-lowering efficacy of febuxostat 80 mg exceeded that of febuxostat 40 mg and allopurinol (300/200 mg), which were comparable. In subjects with mild/moderate renal impairment, both febuxostat doses were more efficacious than allopurinol and equally safe. At the doses tested, safety of febuxostat and allopurinol was comparable.Clinical Trial RegistrationNCT00430248

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Section: Discussionmentioning

confidence: 99%

The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial

et al. 2010

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“…Second, in the real‐life, a sub‐optimal dosing of allopurinol could occur . Indeed, the allopurinol fixed dosage of 300 mg/day could not be appropriate , and in patients with severe gout adherent to allopurinol, who do not reach the recommended sUA levels, the allopurinol dose should be escalated up to 800 mg/day .…”

Section: Discussionmentioning

confidence: 99%

Allopurinol adherence among patients with gout: an Italian general practice database study

et al. 2015

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“…One of these medications was allopurinol whose active metabolite, oxypurinol, is primarily renally cleared. Perhaps the lack of consensus was due to the panel being aware of data that shows that toxicity is uncommon when using doses greater than recommended based on creatinine clearance to reduce uric acid 24,25. Some might also question the lack of consensus for the most commonly used thiazide diuretic, hydrochlorothiazide.…”

Section: Discussionmentioning

confidence: 99%

“…Perhaps the lack of consensus was due to the panel being aware of data that show that toxicity is uncommon when using doses greater than recommended based on creatinine clearance to reduce uric acid. 24,25 Some might also question the lack of consensus for the most commonly used thiazide diuretic: hydrochlorothiazide. Although it is commonly assumed that thiazide diuretics are ineffective in patients with creatinine clearances of less than 30 mL/min, studies have shown these medications to be effective alone or in combination with loop diuretics at this level of renal dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Consensus Guidelines for Oral Dosing of Primarily Renally Cleared Medications in Older Adults

Hanlon

Aspinall

Semla

et al. 2009

J American Geriatrics Society

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Objectives To establish consensus oral dosing guidelines for primarily renally cleared medications prescribed for older adults. Design Two-round modified Delphi Survey. Participants Expert panel of 11 geriatric clinical pharmacists. Measurements After a comprehensive literature search and review by the investigative group of 6 physicians (2 from general internal medicine, 2 nephrologists, 2 geriatricians), 45 dosing recommendations for 30 medications at various levels of renal function were created. The expert panel rated their agreement with each of these 45 dosing recommendations using a 5-point Likert scale (1= strongly disagree to 5=strongly agree). Recommendation-specific means and 95% confidence intervals were estimated. Consensus was defined as a lower 95% confidence limit of >4.0 for the recommendation –specific mean score. Results The response rate was 81.8% (9/11) for the first round. All respondents that completed the first round also completed the second round. The expert panel reached consensus on 26 recommendations involving 18 (60%) medications. For 10 medications (chlorpropamide, colchicine, cotrimoxazole, glyburide, meperidine, nitrofurantoin, probenecid, propoxyphene, spironolactone, and triamterene), the consensus recommendation was not to use the medication in older adults below a specified level of renal function (e.g., creatinine clearance < 30 ml/min). For the remaining 8 medications (acyclovir, amantadine, ciprofloxacin, gabapentin, memantine, ranitidine, rimantadine, and valacyclovir), specific recommendations for dose reduction or interval extension were made. Conclusion An expert panel of geriatric clinical pharmacists was able to reach consensus agreement on a number of oral medications that are primarily renally cleared.

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Optimizing Therapy With Allopurinol: Factors Limiting Hypouricemic Efficacy

Cited by 20 publications

References 31 publications

The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial

The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial

Allopurinol adherence among patients with gout: an Italian general practice database study

Consensus Guidelines for Oral Dosing of Primarily Renally Cleared Medications in Older Adults

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