Allopurinol Dosing in Renal Impairment: Walking the Tightrope Between Adequate Urate Lowering and Adverse Events

  title={Allopurinol Dosing in Renal Impairment: Walking the Tightrope Between Adequate Urate Lowering and Adverse Events},
  author={Nicola Dalbeth and Lisa K. Stamp},
  journal={Seminars in Dialysis},
Allopurinol is the mainstay of urate‐lowering therapy for patients with gout and impaired renal function. Although rare, a life‐threatening hypersensitivity syndrome may occur with this drug. The risk of this allopurinol hypersensitivity syndrome (AHS) is increased in renal impairment. The recognition that AHS may be because of delayed‐type hypersensitivity to oxypurinol, the main metabolite of allopurinol, and that oxypurinol concentrations are frequently elevated in patients with renal… 
A critical reappraisal of allopurinol dosing, safety, and efficacy for hyperuricemia in gout
The emergence of novel urate-lowering therapeutic options, such as febuxostat and uricase, makes timely this review of current allopurinol dosing guidelines, safety, and efficacy in gout hyperuricemia therapy, including patients with chronic kidney disease.
Starting dose is a risk factor for allopurinol hypersensitivity syndrome: a proposed safe starting dose of allopurinol.
It is indicated that starting allopurinol at a dose of 1.5 mg per unit of estimated GFR may be associated with a reduced risk of AHS, and the dose can be gradually increased to achieve the target serum urate level.
An Open‐Label Dose‐Finding Study of Allopurinol to Target Defined Reduction in Urate Levels in Hemodialysis Patients
Determining an optimal dose of allopurinol to use in the hemodialysis population will first help to guide clinicians in their treatment of their HD patients who develop gout, and defining the optimal dose to use was a priority.
Renal dosing of allopurinol results in suboptimal gout care
It is noted that the authors do not provide a recommendation on starting dose for patients with renal impairment , the patient group most likely to benefit from starting at a much lower dose of allopurinol.
The Effect of Allopurinol on Renal Function
Treatment of hyperuricemic patients with allopurinol over an average of 3.4 years resulted in a significant improvement of kidney function in this male cohort from the Veterans Administration Healthcare System, and Clinicians should consider this potential benefit of allopURinol in the treatment of patients withHyperuricemia.
Safety and Efficacy of Febuxostat Treatment in Subjects with Gout and Severe Allopurinol Adverse Reactions
  • S. Chohan
  • Medicine
    The Journal of Rheumatology
  • 2011
Safety and urate-lowering efficacy of febuxostat (FEB), a recently approved non-purine analog inhibitor of XO, was assessed in 13 successively encountered gout patients with prior documented severe allopurinol reactions.
Febuxostat: the evidence for its use in the treatment of hyperuricemia and gout
Febuxostat, at doses ranging from 40 to 240 mg/day, is efficacious in reducing serum urate in patients with hyperuricemia and gout, comparing favorably with fixed doses of allopurinol in that respect.
Febuxostat for the treatment of hyperuricemia in patients with gout
Febuxostat may be a safe and effective alternative for treating gout patients where allopurinol 300 mg/day is neither safe nor effective.
Association of Chronic Kidney Disease With Allopurinol Use in Gout Treatment
In this large cohort, allopurinol initiation of at least 300 mg/d was associated with a lower risk of renal function deterioration, and clinicians should consider evaluating other potential causes when patients with gout experience renal function decline.
Safety profile of anti-gout agents: an update
  • L. Stamp
  • Medicine, Biology
    Current opinion in rheumatology
  • 2014
In general, treatments for gout are well tolerated, although clinicians must keep in mind the potential for drug interactions and the contribution of comorbidities to thepotential for adverse effects with gout therapies.


Relation between adverse events associated with allopurinol and renal function in patients with gout
No increase was seen in the prevalence of adverse reactions to allopurinol in patients who received higher allopURinol maintenance doses than those recommended according to creatinine clearance rate.
Dose adjustment of allopurinol according to creatinine clearance does not provide adequate control of hyperuricemia in patients with gout.
Adherence to published allopurinol dosing guidelines led to suboptimal control of hyperuricemia in this population of patients with gout, and further work is required to clarify the safety and efficacy of allopURinol dose escalation, particularly in patients with renal impairment.
The optimal use of allopurinol: an audit of allopurinol use in South Auckland.
There is poor adherence to the current recommended dosing guidelines for allopurinol and Creatinine clearance rather than plasma creatinine needs to be used to predict the dose of allopURinol.
Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level.
Allopurinol therapy significantly decreases serum uric acid levels in hyperuricemic patients with mild to moderate chronic kidney disease and helps preserve kidney function during 12 months of therapy compared with controls.
The allopurinol hypersensitivity syndrome.
Clinical Pharmacokinetics of Allopurinol
The interaction of allopurinol with oral anticoagulants and phenytoin has not been clearly established in clinical practice, and dosages should be adjusted in patients with renal dysfunction.
Correction of Allopurinol Dosing Should Be Based on Clearance of Creatinine, but Not Plasma Creatinine Levels: Another Insight to Allopurinol-Related Toxicity
Dosage adjustment of allopurinol should be based on clearance of creatinine or estimation of glomerular filtration using the Cockcroft-Gault equation, because Pcr is insensitive enough to detect renal function impairment so that patients may be placed at risk for overdosing side effects.
Plasma oxipurinol concentrations during allopurinol therapy.
In patients with normal renal function, a rise of the plasma xanthine concentration to between 6 and 9 mumol/l suggested a satisfactory degree ofxanthine oxidase inhibition, and these measurements are particularly useful in patients who are still hyperuricaemic despite the usual doses of allopurinol.
Allopurinol dosage selection: relationships between dose and plasma oxipurinol and urate concentrations and urinary urate excretion.
It was apparent that many patients were taking unnecessarily high daily doses of allopurinol and that renal status was not always considered when deciding dosage regimens of allopsinol.
Dosage prescribing and plasma oxipurinol levels in patients receiving allopurinol therapy
Patients with oxipurinol concentrations of up to 100 μmol·1−1 had urate concentrations within the normal reference range, and most patients withOxipur inol concentrations below that level had urates within thenormal reference range.