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# Xanthine oxidase inhibitors

Drugs that cut uric acid production by blocking the last enzyme of purine breakdown. The long-term treatment of gout.

Updated 2026-11-01

## What they are

Allopurinol and febuxostat lower serum urate so that urate crystals dissolve and gout flares, tophi and uric acid stones become less frequent. They prevent attacks over months; they do not treat an attack that has already started.

## Mechanism of action

Xanthine oxidase turns hypoxanthine into xanthine and xanthine into uric acid, the end product of purine breakdown in humans. Allopurinol is a hypoxanthine analogue whose active metabolite, oxipurinol, stays bound to the enzyme's molybdenum centre; febuxostat is not a purine and blocks the channel that leads to the active site. Hypoxanthine and xanthine are more soluble, are reused or excreted, and urate falls.

Target: Xanthine oxidase (xanthine oxidoreductase)

## Key points

- Starting them can trigger gout flares as urate deposits move; colchicine or an anti-inflammatory is given as prophylaxis.
- They also block the inactivation of 6-mercaptopurine: with azathioprine or mercaptopurine, severe marrow suppression; febuxostat is contraindicated with them.
- Allopurinol: HLA-B*58:01 carriers have a higher risk of SJS/TEN and DRESS.
- Febuxostat: boxed warning for cardiovascular death in gout with established cardiovascular disease.
- Neither is used for asymptomatic hyperuricaemia.

## Drugs in this class

- [**Allopurinol** The classic tablet that lowers uric acid in gout and in cancer treatment. A rash is a stop sign: rare but severe skin… Xanthine oxidase](https://durgical.com/en/pharmacology/allopurinol/)
- [**Febuxostat** A non-purine xanthine oxidase blocker for gout when allopurinol fails or cannot be used. It carries a warning about… Xanthine oxidase](https://durgical.com/en/pharmacology/febuxostat/)

## Test yourself

Think of the answer, then tap the question to see it.

## Why can a gout flare happen in the first weeks of allopurinol?

Urate levels change and crystals are mobilised from tissue deposits, which triggers inflammation; flare prophylaxis is given at the start.

## Which immunosuppressant becomes dangerous with a xanthine oxidase inhibitor?

Azathioprine (and mercaptopurine): xanthine oxidase inactivates 6-mercaptopurine, so its active metabolites build up and suppress the marrow.

## How does febuxostat differ chemically from allopurinol?

Febuxostat is not a purine analogue; allopurinol is a hypoxanthine analogue converted to oxipurinol.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [DailyMed - ALLOPURINOL tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0780dc78-d287-d5db-e063-6294a90aa1dd) (DailyMed (U.S. National Library of Medicine), 2023); [DailyMed - FEBUXOSTAT tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=04f80eb2-8171-4e18-93e4-514440e84b75) (DailyMed (U.S. National Library of Medicine), 2023); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 42 (McGraw Hill, 2023).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/classes/xanthine-oxidase-inhibitors/