非布司他(Febuxostat)
Overview
Febuxostat is a potent, non-purine selective inhibitor of xanthine oxidase used for the chronic management of hyperuricemia in patients with gout. It is often prescribed as an alternative for patients who cannot tolerate allopurinol or in whom allopurinol has proven ineffective.
Mechanism of Action
It selectively and potently inhibits both the oxidized and reduced forms of xanthine oxidase, the enzyme responsible for synthesizing uric acid. This robust inhibition effectively lowers serum uric acid levels, facilitating the dissolution of urate crystals and preventing gout attacks.
Dosage and Administration
The recommended starting dose is typically 40 mg once daily. If the target serum uric acid level is not achieved after a few weeks, the dose may be increased to 80 mg or 120 mg daily. Like allopurinol, it can trigger acute gout flares when initiated, requiring concurrent prophylactic therapy.
Side Effects
Common side effects include liver function abnormalities, nausea, joint pain, and rash. Importantly, febuxostat carries a warning regarding an increased risk of cardiovascular death compared to allopurinol, particularly in patients with pre-existing major cardiovascular diseases.
Contraindications
It is contraindicated in patients being treated with azathioprine or mercaptopurine, as febuxostat can fatally increase the blood concentrations of these drugs. Caution is strongly advised in patients with a history of cardiovascular disease or severe hepatic impairment.
Pregnancy and Lactation
There are no adequate and well-controlled studies in pregnant women; it should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether febuxostat is excreted in human milk, so caution is advised during breastfeeding.
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