. 2024 Aug 28;9:212. doi: 10.1038/s41392-024-01916-y

Table 4.

Update on the therapies for the treatment of hyperuricemia

Therapy	Characteristics	The Indications & Mechanisms	Limitations & Adverse Effects	Dosage & Uses	Clinical Benefits
Allopurinol^400,457,458	Xanthine oxidase inhibitor	First-line therapy with wide availability, attaining the targeted UA concentrations is not consistently realized, attributed to various factors such as insufficient SU monitoring, poor adherence to medication, and inadequate dosing.	Hypersensitivity syndrome: rash, eosinophilia, leukocytosis, fever, hepatitis and progressive kidney failure. Eosinophilia, hepatitis, and interstitial nephritis. Severe cutaneous adverse reactions (SCARs).	Mild: 50–100 mg/day PO initially; Increased weekly to 200–300 mg/day; Moderate to severe: 100 mg/day PO initially; Increased weekly to 400-600 mg/day; Maximum PO dosage: 600 mg/day.	For gout treatment and prevention. Reducing cardiovascular and renal outcomes in patients with asymptomatic hyperuricemia. Improve renal function in children.
Febuxostat^400,457,458	Xanthine oxidase inhibitor	A recommended urate-lowering therapy, marginally reduced risk of heart failure exacerbation.	Muscle pain, stomach. Discomfort, skin rashes, diarrhea, and elevations in liver enzymes.	Initial dose: 20–40 mg PO qDay; Increase to 80 mg PO qDay after 2 wk if serum uric acid <6 mg/dL is not achieved.	More effective in reaching the target of serum uric acid under 6 mg/ dl compared to allopurinol. Potential nephroprotective and cardioprotective effects. Lower risk of primary composite event (cerebral, cardiovascular, and renal events and all deaths).
Topiroxostat^406,459,460	Xanthine oxidase inhibitor/ABCG2 inhibitor	Lowering UA levels while maintaining renal function and exhibiting a positive impact on urinary albumin excretion.	Polyarthritis, nasopharyngitis, and increases the risk of liver damage.	Generally: 20 to 80 mg twice daily.	Reduce left ventricular end-diastolic pressure. Exert nephroprotective properties.
Probenecid^461,462	URAT1 and OAT1, OAT3 inhibitor	For the treatment of renal impairment, it impedes the renal elimination of organic anions and concurrently disrupting tubular urate reabsorption.	Gastrointestinal upset, allergic reactions, nephrolithiasis, hypersensitivity reactions.	Moderate to severe: 250 mg PO twice daily for 1 week; Increase to 500 mg PO twice daily to 2 g/day maximum with dosage increases of 500 mg q4 weeks.	Improved cardiac function and increased in vitro cardiomyocyte calcium sensitivity.
Benzbromarone^382,414,463	URAT1 and GLUT9 inhibitor	Lower development of CKD compared to allopurinol. Relevant for addressing renal dysfunction in hyperuricemia.	Rash, elevation in liver enzymes, hepatotoxicity.	Initial dose:12.5–50 mg daily; Maximum PO dosage: 100 mg/day.	Reduced risk of kidney disease progression and lower risk of end-stage renal disease. Reduction in the risk of developing the first gout flare and type 2 diabetes. Reduced endothelial dysfunction.
Lesinurad⁴⁶⁴	URAT1 and OAT4 inhibitor	Indicated in combination with a xanthine oxidase inhibitor for hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor alone.	Kidney failure, cardiovascular events.	Maximum dose: 200 mg PO qDay in combination with a xanthine oxidase inhibitor.	Considered as an add-on-therapy if the serum uric acid target is not reached with XO inhibitors.
Dotinurad⁴²⁰	URAT1 inhibitor	Maintaining a strong serum uric acid lowering effect with less safety concerns, compared to other agents like benzbromarone.	Gouty arthritis and bursitis. Tend to cause kidney damage.	Oral daily dose: 0.5 mg to 4 mg.	Safety in patients with an estimated glomerular filtration rate (eGFR).
Arhalofenate⁴¹⁹	NSAID; URAT1 and OAT4 inhibitor;	The peroxisome proliferator-activated receptor ligand γ modulator that lowers IL-1β levels to offer an additional advantage by potentially decreasing and preventing gout.	Nephrolithiasis potential liver function abnormalities, cardiovascular risks.	Oral daily dose: 200, 400, or 600 mg once/daily.	Significantly reduce the number of gout flares.
Rasburicase⁴⁶⁵	Uricase	Receiving anticancer therapy expected to result in tumor lysis and subsequent elevation of plasma uric acid, not recommended for asymptomatic hyperuricemia.	Uncertain benefits in managing tumor lysis syndrome (TLS) in cancer patients. The adverse effect include anaphylaxis and methemoglobinemia.	Initial dose: 0.2 mg/kg IV infused over 30 min qDay for up to 5 days.	For the prevention and treatment of tumor lysis syndrome.
Pegloticases⁴³⁰	Uricase	Approved for use in adults with gout resistant to conventional therapy, where UA levels remain elevated despite maximum appropriate doses of xanthine oxidase inhibitors or when the use of xanthine oxidase inhibitors is contraindicated.	Infusion reactions, gout flares and anaphylaxis. Increased risk of cardiovascular events.	Initial dose: 8 mg IV infusion q2wk coadministered with methotrexate 15 mg PO qWeek.	In patients with refractory tophaceous gout.
Tranilast^422,424	Anti-inflammatory agent; URAT1, GLUT9 inhibitor	Inhibiting renal transporters URAT1 and GLUT9.	Liver impairment, immune thrombocytopenia, eosinophilic cystitis, and eosinophilic polymyositis.	Varying doses (300 mg, 600 mg, and 900 mg/per day.	Reducing urate crystal associated inflammation.
Ulodesine (BCX4208)⁴²⁷	Inhibitor of purine nucleoside phosphorylase	Inhibiting PNP, ulodesine reduces the substrates available for XO to form uric acid.	Its potential impact on T cells.	Response rates for doses of 5, 10, and 20 mg were 40%, 50%, 45%, and 65%.	Synergistic action when combined with allopurinol, causes dose-dependent reduction in xanthine and hypoxanthine.