Drug reference

lesinurad

Uricosuric agent, URAT-1/OAT-4 inhibitor · Antihyperuricemic

Uricosuric agent, URAT-1/OAT-4 inhibitorAntihyperuricemic

CDSCO approved

EXCRETION

—

not curated

INTERACTIONS

2 major

SEVERE in our sources

PREGNANCY

FDA category + note

Top interactions

DoravirineSevereDatabaseDDInter
LumateperoneSevereDatabaseDDInter

Mechanism

Lesinurad inhibits the URAT-1 and OAT-4 transporters, thereby reducing renal uric acid reabsorption and increasing uric acid excretion.

Indications

Treatment of gout in patients who have not achieved the target serum uric acid levels with an XO inhibitor alone (formerly FDA-approved)

Dosing

Adult: 200 mg/day (formerly marketed dose).

Pharmacokinetics

Onset

Rapidly absorbed after oral administration

Half-life

Approximately 5 h (clearance ~6 L/h)

Bioavailability

Approximately 100% after oral administration

Protein binding

Largely bound to plasma albumin and other plasma proteins (<98%)

Metabolism

CYP2C9 is the major metabolizing enzyme.

Excretion

30% unchanged, and its metabolites are excreted in the urine (>60% of dose) and feces. Renal impairment increases exposure.

Contraindications

Discontinued in the U.S.
Withdrawn in the European Union
Should not be used when renal function is severely reduced (estimated creatinine clearance <45 mL/min)
Must be used together with an XO inhibitor due to renal failure risk
Not recommended for asymptomatic hyperuricemia
Not recommended as monotherapy

Side effects

Common

Headache (~5%)Influenza-like symptoms (~5%)Gastroesophageal reflux (~3%)Increases in blood creatinine levels (1.5- to 2-fold) with combination therapy (approximately 4%)Increases in blood creatinine levels (1.5- to 2-fold) with monotherapy (approximately 8%)

Serious

Acute renal failure (boxed warning, more common when used without an XO inhibitor)
Renal failure (<1% of patients during combination therapy, approximately 9% during monotherapy)
Nephrolithiasis (increased risk when given alone)