AS A PHARMACIST, you'll hear about an advocacy group pushing for withdrawal of the gout med febuxostat (Uloric, Xanthistop) due to concerns it increases mortality. FDA adds Boxed Warning for increased risk of death with gout medicine Uloric (febuxostat), available at: https://www.fda.gov/drugs/drug-safety-and-availability/fda-adds-boxed-warning-increased-risk-death-gout-medicine-uloric-febuxostat.
We know patients with gout are already at elevated cardiovascular risk. Early studies signaled a higher risk of cardiovascular events in patients on febuxostat compared to allopurinol, so FDA required a safety trial. Now the results are in. For every 91 gout patients with cardiovascular (CV) disease treated with febuxostat instead of allopurinol for about 3 years, one will die from CV-related causes. But the findings have limitations and it's too soon to say why febuxostat would increase mortality.
Continue to use allopurinol (Zyloric, NoUric) first for most chronic gout patients and save febuxostat as second-line. Consider whether high-CV-risk patients already taking febuxostat should switch to allopurinol if they can tolerate it with proper dosing. Start allopurinol at 100 mg/day in patients with normal renal function or 50 mg/day if CrCl is 30 mL/min or less. Then titrate every few weeks as needed up to 800 mg/day in normal renal function, or 300 mg/day or even higher in kidney disease.
Advise patients to stop allopurinol immediately if they develop rash, itching, or other hypersensitivity reactions. Consider HLA genotype testing before starting allopurinol in groups at high risk of hypersensitivity such as patients of Han Chinese or Thai descent, or of Korean descent with CrCl below 60 mL/min.
REFERENCES
White WB, Saag KG, Becker MA, Borer JS, Gorelick PB, Whelton A, Hunt B, Castillo M, Gunawardhana L; CARES Investigators. Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout. N Engl J Med. 2018 Mar 29;378(13):1200-1210. Available at: https://pubmed.ncbi.nlm.nih.gov/29527974
Qaseem A, Harris RP, Forciea MA; Clinical Guidelines Committee of the American College of Physicians. Management of Acute and Recurrent Gout: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2017 Jan 3;166(1):58-68. Available at: https://pubmed.ncbi.nlm.nih.gov/27802508
Choi, H., Neogi, T., Stamp, L., Dalbeth, N. and Terkeltaub, R. (2018). New Perspectives in Rheumatology: Implications of the Cardiovascular Safety of Febuxostat and Allopurinol in Patients With Gout and Cardiovascular Morbidities Trial and the Associated Food and Drug Administration Public Safety Alert. Arthritis & Rheumatology, 70(11), pp.1702–1709. Available at: https://onlinelibrary.wiley.com/doi/full/10.1002/art.40583