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Zurampic / lesinurad
Pharmacology
Manufacturer
Approval Date
Indications
Contraindications
Black Box Warnings
Warnings/Precautions
Pregnancy/Lactation
Pharmacokinetics
Drug Interactions –
Object Drugs
Drug Interactions –
Precipitant drugs
Adverse Effects
(Treatment)[Placebo]
Monitoring Efficacy
Monitoring Toxicity
Dosing
Initial/ Usual/ Max
Renal Adjustment
Uric Acid Transporter 1 (URAT1) Inhibitor that lowers serum uric acid levels
and increases renal clearance and fractional excretion of uric acid in
patients with gout.
AstraZeneca Pharmaceuticals
12/2015
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.
 Severe renal impairment, end stage renal disease and kidney
transplant recipients.
 Tumor lysis syndrome or Lesch-Nyhan syndrome
 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
 Renal events: Adverse reactions related to renal function have occurred
after initiating lesinurad. Monitor renal function at initiation and during
therapy with lesinurad, particularly in patients with CrCl < 60 mL/min,
and evaluate for signs and symptoms of acute uric acid nephropathy.
 Cardiovascular events: Major adverse cardiovascular events were
observed with lesinurad; more evaluation is needed.
 Adverse events were not observed in animal reproduction studies.
 All forms of hormonal contraceptives (oral, injectable, topical) may be
less effective during therapy with lesinurad. Additional methods of
contraception are recommended during therapy.
 Unknown excretion in human breast milk
A – Rapid with bioavailability ~100%
D – Mean ss volume of distribution ~20 L, 98% protein bound
M – Oxidative metabolism primarily via CYP2C9
E – Estimated half-life of 5 hours, 63% urine, 32% feces
Sildenafil (30%), Amlodipine (35%), Colchicine (25%), Furosemide
(30%), Indomethacin (30%)
Rifampin (30%), Naproxen (20%), Fluconazole (60%)
Headache (5.3%) [4.1%] Blood creatinine increased (4.3%) [2.3%]
Influenza (5.1%) [2.7%]
Gastroesophageal reflux disease (2.7%) [0.8%]
Decrease in serum urate level
Monitor renal function and side effects
200 mg 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.
Instruct patients to stay well hydrated (~2 liters [68 oz] of liquid per day).
Pre-existing renal impairment:
 Estimated CrCl ≥60 mL/minute: No dosage adjustment necessary.
 Estimated CrCl 45 to <60 mL/minute: No dosage adjustment is
necessary; monitor more frequently.
 Estimated CrCl <45 mL/minute: Treatment may be less effective (based
on limited experience) and should not be initiated.
Renal toxicity during treatment:
 Estimated CrCl persistently <45 mL/minute: Discontinue treatment.
Hepatic Adjustment


Cost:
Brand – Generic
Zurampic – lesinurad
Mild to moderate impairment (Child-Pugh class A and B): No dosage
adjustment necessary.
Severe impairment (Child-Pugh class C): Use is not recommended
(has not been studied).
Dose(s)
200 mg tablet
$ (30d)
Unknown
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 alone.
 Lesinurad must be used in combination with a xanthine oxidase inhibitor and should be taken at
the same time as the xanthine oxidase inhibitor. It is dosed 200 mg by mouth once daily in the
morning with food and water.
 Lesinurad is contraindicated in severe renal impairment and should be avoided in patients with
CrCl < 45mL/min. Lesinurad may cause serum creatinine elevations (generally reversible) and
periodic monitoring is recommended.
References:
1. www.zurampic.com
2. Zurampic package insert. AstraZeneca. Dec. 2015.
3. Roberts, S. “Zurampic Approved for Gout”
https://www.nlm.nih.gov/medlineplus/news/fullstory_156382.html. Accessed March 1, 2016.
4. 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.
Date Prepared: 03/8/2016
Editor: Peter G. Koval, Pharm.D., BCPS
Author: Kristen Gray, Pharm.D. Candidate, UNC Eshelman School of Pharmacy