Febuxostat

Febuxostat, sold under the brand names Uloric among others, is a medication used long-term to treat gout due to high uric acid levels. It is generally only recommended in those who cannot take allopurinol. When initially started, medications such as NSAIDs are often recommended to prevent gout flares. It is taken by mouth. Febuxostat, sold under the brand names Uloric among others, is a medication used long-term to treat gout due to high uric acid levels. It is generally only recommended in those who cannot take allopurinol. When initially started, medications such as NSAIDs are often recommended to prevent gout flares. It is taken by mouth. Common side effects include liver problems, nausea, joint pain, and a rash. Serious side effects include an increased risk of death as compared with allopurinol, Stevens-Johnson syndrome, and anaphylaxis. Use is not recommended during pregnancy or breastfeeding. It inhibits xanthine oxidase, thus reducing production of uric acid in the body. Febuxostat was approved for medical use in the European Union in 2008 and in the United States in 2009. No generic version is available as of 2019, though one has been approved. In the United Kingdom a month of treatment costs the NHS about 24 pounds. In the United States the wholesale cost of a month's worth of medication is about US$320. Febuxostat is used to treat chronic gout and hyperuricemia. Febuxostat is typically only recommended in those who cannot tolerate allopurinol. National Institute for Health and Clinical Excellence concluded that febuxostat is more effective than standard doses of allopurinol, but not more effective than higher doses of allopurinol. Febuxostat is in the US pregnancy category C; there are no adequate and well-controlled studies in pregnant women. The adverse effects associated with febuxostat therapy include nausea, diarrhea, arthralgia, headache, increased hepatic serum enzyme levels and rash. On 15 November 2017, the FDA issued a safety alert indicating that the preliminary results from a safety clinical trial showed an increased risk of heart-related death with febuxostat compared to allopurinol. The FDA required Takeda to conduct this safety study when the medicine was approved in 2009. The febuxostat drug labels already carry a warning and precaution about cardiovascular events because the clinical trials conducted before approval showed a higher rate of heart-related problems in patients treated with febuxostat compared to allopurinol. These problems included heart attacks, strokes, and heart-related deaths. As a result, the FDA required an additional safety clinical trial after the drug was approved and on the market to better understand these differences, and that trial was finished recently.The safety trial was conducted in over 6,000 patients with gout treated with either febuxostat or allopurinol. The primary outcome was a combination of heart-related death, non-deadly heart attack, non-deadly stroke, and a condition of inadequate blood supply to the heart requiring urgent surgery. The preliminary results show that overall, febuxostat did not increase the risk of these combined events compared to allopurinol. However, when the outcomes were evaluated separately, febuxostat showed an increased risk of heart-related deaths and death from all causes. Febuxostat is contraindicated with concomitant use of theophylline and chemotherapeutic agents, namely azathioprine and 6-mercaptopurine, because it could increase blood plasma concentrations of these drugs, and therefore their toxicity. Febuxostat is a non-purine-selective inhibitor of xanthine oxidase. It works by non-competitively blocking the molybdenum pterin center which is the active site on xanthine oxidase. Xanthine oxidase is needed to successively oxidize both hypoxanthine and xanthine to uric acid. Hence, febuxostat inhibits xanthine oxidase, therefore reducing production of uric acid. Febuxostat inhibits both oxidized as well as reduced form of xanthine oxidase because of which febuxostat cannot be easily displaced from the molybdenum pterin site.