Download Lesinurad

Zurampic® - Lesinurad
Manufacturer: AstraZeneca
FDA Approval Date: December 22, 2015
Zurampic® - Lesinurad
Objectives
• At the end of this presentation
participants will be able to:
1. Appropriately recommend Zurampic® -
Lesinurad
2. Effectively educate patients on the
purpose, proper use and potential
adverse effects of Zurampic® Lesinurad
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].
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].
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].
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].
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].
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].
Zurampic® - Lesinurad
Drug Interactions
• Drug Interactions – Object Drugs:
• Sildenafil (30%)
• Amlodipine (35%)
• Colchicine (25%)
• Furosemide (30%)
• Indomethacin (30%)
Zurampic® [package insert].
Zurampic® - Lesinurad
Drug Interactions
• Drug Interactions – Precipitant Drugs:
• Rifampin (30%)
• Naproxen (20%)
• Fluconazole (60%)
Zurampic® [package insert].
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].
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].
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].
Zurampic® - Lesinurad
Literature Review
• RDEA594-203 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.
Zurampic® - Lesinurad
Literature Review
• Design: randomized, double-blind, placebocontrolled 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.
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.
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.
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.
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
4.2
4.1
sUA, mg/dL
6.7
6.4
Years since gout diagnosis
7.3
10.2
Perez-Ruiz F, et al. Ann Rheum Dis 2016;0:1–7.
Zurampic® - Lesinurad
Literature Review
• Results:
Placebo Lesinurad
Reduction from baseline
sUA levels at 4 weeks
P-value
+2.6%
-16%
<0.0001
% of patient who achieved
sUA <6 mg/dL
25%
63%
<0.0001
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.
Zurampic® - Lesinurad
Literature Review
• Safety Endpoints:
Adverse Event
Placebo
Lesinurad
Any
Discontinuation
Death
45.8%
1.4%
0%
45.7%
0%
0%
Common AEs
Headache
Nasopharyngitis
Gout Flare
Arthralgia
1.4%
9.6%
20.8%
5.6%
6.5%
10.5%
21.7%
6.5%
Perez-Ruiz F, et al. Ann Rheum Dis 2016;0:1–7.
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.
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
Zurampic® - Lesinurad
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/fullstor
y_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.