The FDA concluded its months-long investigation into mortality risk with febuxostat (Uloric) by mandating strong warnings on the product label and restricting use.
Approved use is now only after maximally titrated allopurinol (Zyloprim) fails or isn’t tolerated.
Febuxostat will have to carry a black-box warning of increased risk of cardiovascular and all-cause mortality compared with allopurinol, as had been shown in the CARES trial, and update the patient medication guide with that information.
FDA also recommended that clinicians monitor for cardiovascular signs and symptoms for patients on febuxostat.
Since approval in 2009, the label has warned of increased risk of gout flares with initiation of therapy, cardiovascular events, hepatic toxicity, and serious skin reactions.
The additional precautions follow the recommendations of the FDA advisory panel that met in January. It had overwhelmingly voted that the benefits still outweigh the risks for selected patients (e.g., those with serious skin reactions to allopurinol), but most panelists advocated second-line use for the general gout population.