Garry G Graham1,2, Sophie L Stocker3,4, Diluk R W Kannangara1,2,5,6, Richard O Day1,2,5. 1. Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, NSW, Australia. 2. School of Medical Sciences, University of New South Wales, Kensington, NSW, Australia. 3. Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, NSW, Australia. sophie.stocker@svha.org.au. 4. St Vincent's Clinical School, St Vincent's Hospital, University of New South Wales, Kensington, Sydney, Australia. sophie.stocker@svha.org.au. 5. St Vincent's Clinical School, St Vincent's Hospital, University of New South Wales, Kensington, Sydney, Australia. 6. School of Medicine, University of Notre Dame, Sydney, Australia.
Abstract
PURPOSE OF REVIEW: To review the extent of treatment success or failure with the xanthine oxidoreductase inhibitors allopurinol and febuxostat and indicate how the dosage of urate-lowering therapy (ULT) may be modified to increase the response in the majority of patients with gout. RECENT FINDINGS: Gout flares are associated with serum concentrations of urate above 0.42 mmol/L (7 mg/dL). Achieving and maintaining serum urate below 0.36 mmol/L is considered an effective response to ULT. On an intention to treat basis, clinical trials indicate that allopurinol at daily doses of 100 to 300 mg decreases serum urate adequately in only about 40% of gout patients while febuxostat 80 mg daily reduces serum urate adequately in approximately 70% of gout patients. Higher doses of ULT may be required in patients receiving concomitant diuretics. The addition of a uricosuric agent to allopurinol and febuxostat therapy significantly increases the proportion of patients achieving adequate lowering of serum urate. Finally, carriers of a genetic variant of the transporter, ABCG2 (BCRP), have a decreased response to allopurinol. Careful examination of medication adherence, titration of doses, and the addition of uricosuric agents increase the percentage of patients responding to allopurinol and febuxostat.
PURPOSE OF REVIEW: To review the extent of treatment success or failure with the xanthine oxidoreductase inhibitors allopurinol and febuxostat and indicate how the dosage of urate-lowering therapy (ULT) may be modified to increase the response in the majority of patients with gout. RECENT FINDINGS:Gout flares are associated with serum concentrations of urate above 0.42 mmol/L (7 mg/dL). Achieving and maintaining serum urate below 0.36 mmol/L is considered an effective response to ULT. On an intention to treat basis, clinical trials indicate that allopurinol at daily doses of 100 to 300 mg decreases serum urate adequately in only about 40% of goutpatients while febuxostat 80 mg daily reduces serum urate adequately in approximately 70% of goutpatients. Higher doses of ULT may be required in patients receiving concomitant diuretics. The addition of a uricosuric agent to allopurinol and febuxostat therapy significantly increases the proportion of patients achieving adequate lowering of serum urate. Finally, carriers of a genetic variant of the transporter, ABCG2 (BCRP), have a decreased response to allopurinol. Careful examination of medication adherence, titration of doses, and the addition of uricosuric agents increase the percentage of patients responding to allopurinol and febuxostat.
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