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Content Update

August 7, 2019

FDA Warns of Increased Risk of Death with Febuxostat in Patients with Gout and Cardiovascular Disease: In February 2019, the U.S. Food and Drug Administration issued a new boxed warning and Medication Guide for febuxostat (Uloric), a xanthine oxidase inhibitor used to lower serum uric acid concentrations in patients with gout. In a randomized controlled study (the CARES trial), febuxostat was associated with an increased risk of cardiovascular death and death from any cause when compared with allopurinol. Based on the labeling change, febuxostat should only be prescribed for patients who have had an inadequate response, intolerance, or contraindications to allopurinol. Patients should be informed of the potential for adverse cardiovascular events and advised to notify their healthcare provider if cardiovascular symptoms occur.


For the chapter in the Wells Handbook, please go to Chapter 1. Gout and Hyperuricemia.



  • image In the absence of a history of gout, asymptomatic hyperuricemia may not require treatment.

  • image Acute gouty arthritis may be treated effectively with short courses of high-dose nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or colchicine.

  • image Low-dose colchicine is highly effective at relieving acute attacks of gout; dose titration leads to more adverse effects but does not improve efficacy.

  • image Treatment with urate-lowering drugs to reduce risk of recurrent attacks of gouty arthritis is considered cost-effective for patients having two or more attacks of gout per year.

  • image Xanthine oxidase inhibitors are efficacious for the prophylaxis of recurrent gout attacks in both underexcreters and overproducers of uric acid. Either allopurinol or febuxostat should be initiated in patients with one of the following indications for urate-lowering therapy (ULT): (a) two or more gout attacks per year, (b) the presence of one or more tophus, (c) chronic kidney disease (stage 2 or worse), or (d) a history of urolithiasis. The dose of the xanthine oxidase inhibitor should be titrated to a goal serum urate concentration of less than 6 mg/dL (less than 357 μmol/L) (or less than 5 mg/dL [less than 297 μmol/L] if signs of gout persist at a level of 6 mg/dL [357 μmol/L]).

  • image Uricosuric agents should be avoided for patients with renal impairment (a creatinine clearance below 50 mL/min [0.83 mL/s]), a history of renal calculi, or overproduction of uric acid.

  • image Low-dose colchicine, NSAID, or corticosteroid therapy should be administered during the first 3 to 6 months of urate-lowering therapy (ULT) to minimize the risk of acute gout attacks that may occur during this initiation period.

  • image Uric acid nephrolithiasis should be treated with adequate hydration (2-3 L/day), a daytime urine-alkalinizing agent, and 60 to 80 mEq/day (mmol/day) of potassium bicarbonate or potassium citrate.

  • image Patients with hyperuricemia or gout should undergo comprehensive evaluation for signs and symptoms of cardiovascular disease, and aggressive management of cardiovascular risk factors (ie, weight loss, reduction of alcohol intake, control of blood pressure, glucose, and lipids) ...

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