Allopurinol Versus Febuxostat – Clinical Comparison

Lowering uric acid is the key to reducing gout flares. Both allopurinol (podcast) and febuxostat are effective at performing this task. However, there are some considerations you need to be aware when deciding to utilize allopurinol versus febuxostat. I’ll break down some of those comparisons in this article.

From a mechanism of action standpoint, allopurinol and febuxostat are the same. Both are xanthine oxidase inhibitors. Inhibition of the enzyme leads to reduced formation of uric acid and can ultimately help lower uric acid levels and reduce the risk of gout flares.

Cost is a major concern with febuxostat and puts a checkmark in the allopurinol favorability box. A quick search on GoodRx demonstrates that the cost of febuxostat can be 5-10X (or more) compared to allopurinol.

What about drug interactions when comparing allopurinol versus febuxostat? Allopurinol has a few more drug interactions listed in a drug interactions checker than febuxostat. However, the major interaction with azathioprine due to xanthine oxidase inhibition exists with both of these medications. I’ve discussed this interaction further in this previous post. Mercaptopurine and theophylline would also be affected, but in practice, I see these drugs even less frequently than azathioprine.

Pharmacogenomic considerations are important with allopurinol. Recall that patients with the HLA-B*5801 allele are at greater risk for skin reactions. Testing for this allele is recommended in patients who are at greater risk of this genetic variation. Patients of Asian and African descent are at the highest risk. I’ve discussed this and other genetic tests that often show up on board exams in the past – you can find a free sample video on pharmacogenomics here!

Let’s finally deal with the elephant in the room and one of the primary reasons that you seldom see the use of febuxostat. Febuxostat has received a boxed warning from the FDA for an increased risk of cardiovascular events as compared to allopurinol. Obviously, this is not good and should give you some reservations about using the medication. In addition, the FDA warning goes on to recommend reserving its use for patients who’ve failed or cannot tolerate allopurinol.

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Written By Eric Christianson

September 11, 2022

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