Zurampic (lesinurad) inhibits the urate transporter, URAT1, which is responsible for the majority of the renal reabsorption of uric acid. By inhibiting URAT1, Zurampic increases uric acid excretion and thereby lowers serum uric acid.
Zurampic is specifically indicated in combination with a xanthine oxidase inhibitor for the treatment of hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor alone.
Zurampic is supplied as tablets for oral administration. The recommended dose is 200 mg once daily in combination with a xanthine oxidase inhibitor, including allopurinol or febuxostat. The maximum daily dose of Zurampic is 200 mg. Failure to take Zurampic with a xanthine oxidase inhibitor may increase the risk of renal adverse reactions. Zurampic tablets should be taken in the morning with food and water. Patients should be instructed to stay well hydrated. Assess renal function before initiating Zurampic. Do not initiate Zurampic if eCLcr is below 45 mL/min. Discontinue Zurampic if eCLcr persistently falls below 45 mL/min.
The FDA approval of Zurampic was based on three phase III studies, CLEAR1, CLEAR2 and CRYSTAL. CLEAR1 and CLEAR2 evaluated the efficacy and safety of a once daily dose of Zurampic in combination with allopurinol compared to allopurinol alone. Zurampic when used in combination with allopurinol, met the primary endpoint in both studies with approximately twice as many patients achieving the serum uric acid (sUA) goal of <6.0mg/dL (360 µmol/L) by month 6, compared to those treated with allopurinol alone. The CRYSTAL study evaluated the efficacy and safety of a once daily dose of Zurampic in combination with febuxostat 80mg compared to febuxostat 80mg alone in gout patients with tophi (visible deposits of urate crystals in joints and skin). Patients were administered febuxostat 80mg orally once daily for 3 weeks before randomization. Results showed Zurampic 200mg in combination with febuxostat demonstrated greater (nominal p<0.05) sUA lowering to the target for tophaceous gout of <5.0mg/dL (300 µmol/L) compared to febuxostat alone at all months except at the time of the primary endpoint, month 6 (56.6% vs. 46.8%, non significant). In the subgroup of patients with baseline sUA =5.0mg/dL (300 µmol/L) (i.e. those above recommended sUA treatment target for tophaceous gout on febuxostat alone), Zurampic 200mg in combination with febuxostat resulted in more subjects reaching target sUA of <5.0mg/dL (300 µmol/L) compared to febuxostat alone at month 6.
Adverse effects associated with the use of Zurampic may include, but are not limited to, the following:
Zurampic comes with a boxed warning. Acute renal failure has occurred with Zurampic and was more common when Zurampic was given alone. Zurampic should be used in combination with a xanthine oxidase inhibitor.
Zurampic (lesinurad) reduces serum uric acid levels by inhibiting the function of transporter proteins involved in uric acid reabsorption in the kidney. Lesinurad inhibited the function of two apical transporters responsible for uric acid reabsorption, uric acid transporter 1 (URAT1) and organic anion transporter 4 (OAT4), with IC50 values of 7.3 and 3.7 µM, respectively. URAT1 is responsible for the majority of the reabsorption of filtered uric acid from the renal tubular lumen. OAT4 is a uric acid transporter associated with diuretic-induced hyperuricemia. Lesinurad does not interact with the uric acid reabsorption transporter SLC2A9 (Glut9), located on the basolateral membrane of the proximal tubule cell.
For additional information regarding Zurampic or hyperuricemia associated with gout, please visit https://www.zurampic.com/