STEPS New Drug Reviews (Zurampic) for Phung C. On, PharmD, BCPS Massachusetts College of Pharmacy and Health Sciences University, Boston, Massachusetts

Lesinurad (Zurampic) is a agent labeled for the treatment of hyperurice- Drug Dosage Dose form Cost* mia that is associated with gout. It should Lesinurad 200 mg 200-mg tablet $394 be used in patients who are already tak- (Zurampic) once daily ing appropriate doses of a xanthine oxi- *—Estimated retail price of one month’s treatment based on infor- dase inhibitor such as , but mation obtained at http://www.goodrx.com (accessed September who have not yet reached target levels of 28, 2017). serum .1

Safety Lesinurad can cause acute renal failure if taken hormonal contraceptives; therefore, women tak- without a xanthine oxidase inhibitor, at a higher ing lesinurad should use additional methods of dose than recommended, or by patients with contraception. Daily dosages of greater moderately reduced renal function ( than 325 mg may increase uric acid levels, reduc- clearance less than 45 mL per minute per 1.73 m2 ing the effect of uric acid treatment.1 Safety has [0.75 mL per second per m2]).1 Renal function not been established in pregnant or breastfeeding should be monitored in all patients, especially women.1 those with a creatinine clearance less than 60 mL per minute per 1.73 m2 (1.00 mL per second Tolerability per m2) or who have increased levels of serum Lesinurad used in combination with a xanthine creatinine. Lesinurad should be discontinued in oxidase inhibitor is well tolerated. In clinical tri- patients with symptoms of uric acid nephropathy als, the most common adverse effects (i.e., affect- or serum creatinine elevations 1.5 to 2 times the ing more than 2% of patients) were headache, pretreatment value.1 In premarketing research, influenza, and gastroesophageal reflux disease.1,2 major adverse cardiovascular events occurred at Approximately 3% to 8% of patients discontinue a slightly higher rate in patients taking lesinurad therapy because of adverse effects.3,4 vs. those taking placebo, especially at higher- than-recommended doses.1 Effectiveness Lesinurad is metabolized in the by the Adding lesinurad therapy has been shown to cytochrome P450 (CYP450) 2C9 enzyme system. decrease serum uric acid levels in patients with an It may affect the blood levels of other average uric acid concentration of 7.0 mg per dL metabolized by this system, and it may be affected (416 µmol per L) who are already taking at least by these other medications, although the degree 300 mg per day of allopurinol. Approximately to which these interactions are clinically relevant one-half (55.4%) of patients will achieve uric acid is unknown. Lesinurad may reduce the reliability levels of less than 6.0 mg per dL (357 µmol per L; of oral, injectable, transdermal, and implantable number needed to treat for six months = 3; 95%

STEPS new drug reviews cover Safety, Tolerability, Effectiveness, Price, and Simplicity. Each independent review is provided by authors who have no financial association with the drug manufacturer. This series is coordinated by Allen F. Shaughnessy, PharmD, MMedEd, Contributing Editor. A collection of STEPS published in AFP is available at http://www.aafp.org/afp/steps. Author disclosure: No relevant financial affiliations.

Downloaded374 American from the Family American Physician Family Physician website at www.aafp.org/afp.www.aafp.org/afp Copyright © 2018 American Academy ofVolume Family Physicians.97, Number For 6 the ◆ March private, 15, noncom 2018- mercial use of one individual user of the website. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests. STEPS

confidence interval, 2.5 to 4.7).3 However, over one year, Bottom Line lesinurad will not reduce the likelihood of a gout flare-up or Lesinurad taken in addition to a xanthine oxidase inhibitor improve tophus resolution in patients with six or fewer epi- reduces serum uric acid levels. However, it does not reduce sodes per year. It has not been studied in patients with more the likelihood of experiencing a gout flare-up or completely frequent episodes.3,4 It has also not been studied to deter- resolving tophi. Although lesinurad may be useful as an mine its effect on the rate of uric acid nephropathy, and it add-on therapy for patients who require once-daily dosing has not been compared with other uricosuric agents added of uricosuric agents, it is much more expensive than current to allopurinol, such as . therapy. Address correspondence to Phung C. On, PharmD, BCPS, at Price phung.​[email protected]. Reprints are not available from the author. A one-month supply of lesinurad costs approximately $394. It is significantly more expensive than probenecid, which References costs about $34 for a 30-day supply. In addition, a one- 1. DailyMed. Drug label information: Zurampic—lesinurad tablet, film coated. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?​setid=​92​ month supply of allopurinol costs about $10. d​61​4a3-​760d-492c-930d-22f​91ff​016​b1. Accessed March 15, 2017. 2. U.S. Food and Drug Administration. FDA approves Zurampic to treat Simplicity high blood uric acid levels associated with gout. December 22, 2015. Lesinurad in a dosage of 200 mg per day should be taken http://www.fda.gov/NewsEvents/Newsroom/Press​Announcements/ ucm478791.htm​ . Accessed March 31, 2017. with food and water at the same time as the morning dose 3. Bardin T, Keenan RT, Khanna PP, et al. Lesinurad in combination with of the xanthine oxidase inhibitor (at least 300 mg of allo- allopurinol: a randomised, double-blind, placebo-controlled study in purinol or an equivalent). Prophylaxis for mobilization patients with gout with inadequate response to standard of care (the gout, such as treatment with (Colcrys, Mitig- multinational CLEAR 2 study). Ann Rheum Dis. 2017;76(5):811-820. are), should be started at the beginning of therapy. Patients 4. Saag KG, Fitz-Patrick D, Kopicko J, et al. Lesinurad combined with allo- purinol: a randomized, double-blind, placebo-controlled study in gout should stop taking lesinurad if the xanthine oxidase inhib- patients with an inadequate response to standard-of-care allopurinol (a itor is discontinued. US-based study). Arthritis Rheumatol. 2017;69(1):203-212. ■

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