febuxostat

xanthine oxidase inhibitor· Brands: Adenuric, Uloric, FeburicPO

Mechanism of action

Febuxostat is a selective xanthine oxidase inhibitor. It blocks the conversion of hypoxanthine to xanthine and xanthine to uric acid, thereby reducing uric acid production. Unlike allopurinol, it does not inhibit other enzymes in the purine pathway.

Pharmacokinetics

Febuxostat is absorbed orally with an absolute bioavailability of approximately 49%.

Indications & dosing

Chronic management of hyperuricemia in gout

Start at 40 mg; increase to 80 mg if serum uric acid not controlled. Not recommended in severe renal impairment (eGFR <30 mL/min).

adult · PO: 40–80 mg once daily · Start at 40 mg; increase to 80 mg if serum uric acid not controlled. Not recommended in severe renal impairment (eGFR <30 mL/min).

Prevention of tumor lysis syndrome (off-label)off-label

Used when allopurinol is contraindicated or not tolerated. Monitor serum uric acid closely.

adult · PO: 40–80 mg once daily · Used when allopurinol is contraindicated or not tolerated. Monitor serum uric acid closely.

Contraindications & precautions

Concurrent therapy with azathioprine or mercaptopurine · Febuxostat inhibits xanthine oxidase, increasing azathioprine and mercaptopurine toxicity. Avoid co-administration.
Severe hepatic impairment (Child-Pugh class C) · No studies in severe hepatic impairment; avoid use.
Hypersensitivity to febuxostat · Includes anaphylaxis and skin reactions.
Pregnancy and breastfeeding · Not recommended; use only if clearly necessary and benefits outweigh risks.
Severe renal impairment (CrCl < 30 mL/min) · Limited data; use with caution.
Established cardiovascular disease · Higher risk of cardiovascular death observed; weigh risks and benefits.
Monitor liver function before and during treatment; discontinue if transaminases rise significantly.
Use with caution in patients with ischaemic heart disease or prior cardiovascular events.
May cause gout flares when initiated; consider prophylactic anti-inflammatory therapy for the first 6 months.
Do not use in patients with severe renal impairment unless benefits outweigh risks; dose adjustment may be needed in moderate impairment.
Advise patients to report symptoms of skin reactions or liver dysfunction promptly.

Adverse effects

Liver function abnormalitiesserious
Nausea
Arthralgia
Rash
Cardiovascular events (including cardiovascular death)serious
Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)serious
Hepatotoxicityserious

Interactions

azathioprinecontraindicatedThe combination is contraindicated. Do not prescribe febuxostat with azathioprine. If no alternative urate-lowering therapy is suitable, consider referral to a specialist for management. If combination is deemed absolutely necessary despite the contraindication, extreme caution is required, with substantial dose reduction of azathioprine and frequent monitoring of full blood counts; however, this is rarely acceptable clinical practice.

Renal & hepatic adjustment

eGFR 30–89: No dose adjustment required.
eGFR 0–29: Use with caution; limited data. Not recommended in severe renal impairment or end-stage renal disease. (avoid)
Hepatic impairment (mild): No dose adjustment required.
Hepatic impairment (moderate): No dose adjustment required.
Hepatic impairment (severe): Not recommended due to lack of data. (avoid)

Monitoring, pregnancy & toxicity

Serum uric acid · Periodically, to assess response
Liver function tests (ALT, AST) · At baseline and periodically
Signs and symptoms of gout flare · During initial therapy
Cardiovascular events (e.g., myocardial infarction, stroke) · Monitor for signs and symptoms
Pregnancy: Not recommended during pregnancy. Use only if clearly needed and after specialist consultation.
Toxicity: Nausea, diarrhoea, headache, dizziness, paraesthesia · Supportive care. No specific antidote.
Toxicity: Hepatotoxicity (elevated liver enzymes) · Discontinue treatment and monitor liver function.
Toxicity: Gout flare during initial treatment · Prophylaxis with NSAID or colchicine; continue febuxostat.

Clinical notes

Febuxostat is indicated for the treatment of chronic hyperuricaemia in gout. It is used when allopurinol is contraindicated or not tolerated. Due to an increased risk of cardiovascular death, febuxostat should be avoided in patients with established cardiovascular disease. It is not recommended for asymptomatic hyperuricaemia. Initiate doses and titrate based on serum uric acid levels. Monitor liver function periodically. Note that gout flares may increase during initiation, so prophylaxis with an NSAID or colchicine is often needed.

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BNF; local formulary