1. Manufacturer: AstraZeneca FDA Approval Date: December 22, 2015
Zurampic® - Lesinurad
Manufacturer: AstraZeneca
FDA Approval Date: December 22, 2015

2. Zurampic® - Lesinurad Objectives
At the end of this presentation participants will be able to:
Appropriately recommend Zurampic® - Lesinurad
Effectively educate patients on the purpose, proper use and potential adverse effects of Zurampic® - Lesinurad

3. Zurampic® - Lesinurad Clinical Application
Indications:
In combination with a xanthine oxidase inhibitor for the treatment of hyperuricemia associated with gout
Place in therapy:
Patients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor alone
Zurampic® [package insert].

4. Zurampic® - Lesinurad Clinical Application
Contraindications:
Severe renal impairment, end stage renal disease, and kidney transplant recipients
Tumor lysis syndrome or Lesch-Nyhan syndrome
Zurampic® [package insert].

5. Zurampic® - Lesinurad Clinical Application
Black Box Warnings
Acute renal failure has occurred with lesinurad and was more common when lesinurad was given alone
Lesinurad should only be used in combination with a xanthine oxidase inhibitor
Zurampic® [package insert].

6. Zurampic® - Lesinurad Clinical Application
Pregnancy:
No available human data
No teratogenicity or effects on fetal development were observed in animal studies
Lactation:
Unknown excretion in human breast milk
Zurampic® [package insert].

7. Zurampic® - Lesinurad Drug Facts
Pharmacology:
Uric Acid Transporter 1 (URAT1) Inhibitor
URAT1 is responsible for the majority of the reabsorption of filtered uric acid from the renal tubular lumen
Zurampic® [package insert].

8. Zurampic® - Lesinurad Drug Facts
Pharmacokinetics: A
Rapid with bioavailability ~100% D
Mean ss volume of distribution ~20 L M
Metabolized primarily via CYP2C9 E
Estimated half-life of 5 hours
Zurampic® [package insert].

9. Zurampic® - Lesinurad Drug Interactions
Drug Interactions – Object Drugs:
Sildenafil (30%)
Amlodipine (35%)
Colchicine (25%)
Furosemide (30%)
Indomethacin (30%)
Zurampic® [package insert].

10. Zurampic® - Lesinurad Drug Interactions
Drug Interactions – Precipitant Drugs:
Rifampin (30%)
Naproxen (20%)
Fluconazole (60%)
Zurampic® [package insert].

11. Zurampic® - Lesinurad Adverse Effects
Common Adverse Effects:
Headache (5.3%) [4.1%]
Influenza (5.1%) [2.7%]
Increased blood creatinine (4.3%) [2.3%]
Gastroesophageal reflux disease (2.7%) [0.8%]
Zurampic® [package insert].

12. Zurampic® - Lesinurad Monitoring Parameters
Efficacy Monitoring:
Serum uric acid levels every 2 to 5 weeks during uric acid lowering therapy titration then every 6 months
Toxicity Monitoring:
SCr and CrCl
Zurampic® [package insert].

13. Zurampic® - Lesinurad Prescription Information
Dosing:
200mg by mouth daily
Administer in the morning with food and water at the same time in the morning as the dose of xanthine oxidase inhibitor
Cost: Unknown
Zurampic® [package insert].

14. Zurampic® - Lesinurad Literature Review
RDEA Study
Purpose: To assess the efficacy and tolerability of lesinurad in combination with allopurinol vs. allopurinol alone in patients with an inadequate response to allopurinol
Perez-Ruiz F, et al. Ann Rheum Dis 2016;0:1–7.

15. Zurampic® - Lesinurad Literature Review
Design: randomized, double-blind, placebo- controlled trial
Conducted in: Canada, Georgia, Poland, Spain, Ukraine, the UK, and the USA
November 2009 to January 2011
Perez-Ruiz F, et al. Ann Rheum Dis 2016;0:1–7.

16. Zurampic® - Lesinurad Literature Review
Inclusion Criteria
Exclusion Criteria
Men and postmenopausal or surgically sterile women
18–80 years old
Gout diagnosis
Inadequate urate-lowering response (sUA ≥6 mg/dL on
≥2 occasions ≥2 weeks apart) to allopurinol monotherapy 200–600 mg daily for ≥6 weeks and sUA ≥6 mg/dL at screening
History of kidney stones
Active liver disease
History of cardiac abnormalities
Long-term use of medications that would worsen gout
Uncontrolled hypertension
SCr >1.5 mg/dL or CrCl <60 mL/min
BMI >48 kg/m2
Perez-Ruiz F, et al. Ann Rheum Dis 2016;0:1–7.

17. Zurampic® - Lesinurad Literature Review
Lesinurad 200mg with allopurinol vs. allopurinol alone
Primary Endpoint:
Percent reduction from baseline sUA levels at 4 weeks
Perez-Ruiz F, et al. Ann Rheum Dis 2016;0:1–7.

18. Zurampic® - Lesinurad Literature Review
Secondary Endpoint:
Proportion of patients with sUA <6, <5 and <4 mg/dL at each visit
Percent change from baseline in 24 h urine UA after 4 weeks
Perez-Ruiz F, et al. Ann Rheum Dis 2016;0:1–7.

19. Zurampic® - Lesinurad Literature Review
Baseline Characteristics:
Placebo
(N = 302)
Lesinurad
(N = 599)
Age
Male
White
51.1
98.6%
93.1%
52.9
95.7%
91.3%
Gout history
Flares in 12 months
sUA, mg/dL
Years since gout diagnosis
4.2
6.7
7.3
4.1
6.4
10.2
Perez-Ruiz F, et al. Ann Rheum Dis 2016;0:1–7.

20. Zurampic® - Lesinurad Literature Review
Results:
Placebo
Lesinurad
P-value
Reduction from baseline sUA levels at 4 weeks
+2.6%
-16%
<0.0001
% of patient who achieved sUA <6 mg/dL
25%
63%
Mean % change from baseline in renal UA clearance at 4 weeks 8%
43.7%
<0.05
Perez-Ruiz F, et al. Ann Rheum Dis 2016;0:1–7.

21. Zurampic® - Lesinurad Literature Review
Safety Endpoints:
Adverse Event
Placebo
Lesinurad
Any
Discontinuation
Death
45.8%
1.4% 0%
45.7%
Common AEs
Headache
Nasopharyngitis
Gout Flare
Arthralgia
9.6%
20.8%
5.6%
6.5%
10.5%
21.7%
Perez-Ruiz F, et al. Ann Rheum Dis 2016;0:1–7.

22. Zurampic® - Lesinurad Literature Review
Trial Conclusion:
Lesinurad decreased sUA levels by 16% from baseline after 4 weeks of treatment when used in combination with allopurinol
63% of patients on lesinurad achieved sUA <6 mg/dL
Perez-Ruiz F, et al. Ann Rheum Dis 2016;0:1–7.

23. Zurampic® - Lesinurad Summary
Zurampic, lesinurad, is first-in-class of Uric Acid Transporter 1 (URAT1) Inhibitor
It is indicated for the treatment of hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor (XOI) alone
Dosed: 200 mg by mouth once daily in the morning with food and water
Contraindicated in severe renal impairment and should be avoided in patients with CrCl < 45mL/min
Can cause serum creatinine elevations (generally reversible) – periodically monitor

24. Zurampic® - Lesinurad References
Zurampic package insert. AstraZeneca. Dec
Roberts, S. “Zurampic Approved for Gout” y_ html. Accessed March 1, 2016.
Perez-Ruiz F, et al. Lesinurad in combination with allopurinol: results of a phase 2, randomised, double-blind study in patients with gout with an inadequate response to allopurinol. Ann Rheum Dis 2016;0:1–7.