Mechanism of uric acid rebound after discontinuation of febuxostat/fibril

Febuxostat (Febuxostat) is a xanthine oxidase inhibitor that reduces the production of uric acid by inhibiting the activity of xanthine oxidase in the body. It is widely used to treat gout and hyperuricemia. Gout is a disease caused by the deposition of urate crystals in joints and soft tissues. Its most typical manifestations are joint redness, swelling and pain. Febuxostat works by lowering serum uric acid levels and reducing the formation of these crystals, thereby relieving patients' symptoms and reducing the frequency of gout attacks.

However, uric acid rebound after discontinuation of febuxostat is a common clinical problem. Specifically, the serum uric acid level will rise rapidly after stopping the drug, even higher than the level before treatment. This is mainly due to the disappearance of the inhibitory effect of the drug, the recovery of xanthine oxidase activity, and the increase in uric acid production again, causing the serum uric acid level to rebound. The mechanism of uric acid rebound can be analyzed from the following aspects.

First, febuxostat reduces the production of uric acid in the body by inhibiting xanthine oxidase. When the drug is used for a long time, serum uric acid levels are effectively controlled, and patients usually experience a reduction in gout symptoms and relief of joint inflammation. After stopping the drug, although the inhibitory effect of xanthine oxidase stops immediately, the urate crystals accumulated in the patient's body are not completely eliminated. Instead, the rapid increase in uric acid levels may trigger a gout attack again.

Secondly, the speed of uric acid rebound is related to the patient's underlying pathological state, the duration of drug use, and the adjustment method after drug withdrawal. If a patient is in a state of hyperuricemia for a long time, after stopping the drug, the existing urate crystals in the body will be re-released into the joints and soft tissues, leading to an acute attack of gout. This usually occurs within days to weeks after stopping the drug and may be more severe than the gout attack during the initial treatment.

Reference materials:https://go.drugbank.com/drugs/DB04854