Company: Ardea Biosciences
Approval Status: Approved August 2017
Specific Treatments: hyperuricemia associated with gout
Duzallo combines two medications with complementary mechanisms of action: lesinurad, a uric acid reabsorption inhibitor, and allopurinol, a xanthine oxidase inhibitor. Duzallo lowers serum uric acid levels by increasing excretion and inhibiting production of uric acid.
Duzallo is specifically indicated for the treatment of hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with a medically appropriate daily dose of allopurinol alone.
Duzallo is supplied as a tablet for oral administration. The recommended dose of Duzallo is one 200 mg lesinurad/300 mg allopurinol tablet per day (or one 200 mg lesinurad/200 mg allopurinol tablet per day for patients with renal impairment (45 – < 60 mL/min eCLcr) on a medically appropriate dose of 200 mg allopurinol. Use one tablet of Duzallo in place of an equivalent portion of the total daily allopurinol dose. The total daily dose of allopurinol should be maintained at the time of initiating Duzallo. One tablet of Duzallo contains the maximum daily lesinurad dose (200 mg). Do not take more than 1 tablet of Duzallo per day. Do not combine Duzallo with Zurampic (lesinurad). Use of Duzallo is not recommended for patients taking daily doses of allopurinol less than 300 mg (or less than 200 mg in patients with moderate renal impairment). Duzallo tablets should be taken in the morning with food and water. Patients should be instructed to stay well hydrated. Assess renal function before initiating Duzallo and do not initiate if eCLcr is below 45 mL/min. Discontinue Duzallo if eCLcr persistently falls below 45 mL/min.
The FDA approval of Duzallo was based on the clinical program supporting the Zurampic (lesinurad) new drug application (NDA) and a pharmacokinetic study that evaluated the bioequivalence of the fixed-dose combination of lesinurad and allopurinol compared to co-administration of separate lesinurad and allopurinol tablets. The efficacy and safety of lesinurad plus allopurinol were demonstrated in two pivotal Phase III clinical trials, CLEAR 1 (n=402) and CLEAR 2 (n=410), which supported the Zuramoic NDA. In clinical trials of adult patients with gout who failed to achieve target sUA levels on allopurinol alone, lesinurad in combination with allopurinol nearly doubled the number of patients who achieved sUA target of <6 mg/dL at month 6, reduced the mean sUA level to <6 mg/dL by month 1 and maintained that level through month 12.
Adverse effects associated with the use of Duzallo may include, but are not limited to, the following:
- blood creatinine increased
- gastroesophageal reflux disease
- skin rash
The Duzallo label comes with the following warning: Acute renal failure has occurred with lesinurad, one of the components of Duzallo. Renal function should be monitored at initiation and during therapy with Duzallo, particularly in patients with eCLcr below 60 mL/min, and evaluated for signs and symptoms of acute uric acid nephropathy.
Mechanism of Action
Duzallo combines two medications with complementary mechanisms of action. Lesinurad reduces serum uric acid levels by inhibiting the function of transporter proteins involved in uric acid reabsorption in the kidney. Allopurinol acts on purine catabolism, without disrupting the biosynthesis of purines. It reduces the production of uric acid by inhibiting the biochemical reactions immediately preceding its formation. Allopurinol is a structural analogue of the natural purine base, hypoxanthine. It is an inhibitor of xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine and of xanthine to uric acid, the end product of purine metabolism in humans. Allopurinol is metabolized to the corresponding xanthine analogue, oxypurinol (alloxanthine), which also is an inhibitor of xanthine oxidase.
For additional information regarding Duzallo or hyperuricemia, please visit http://duzallohcp.com/