Lesinurad- Zuampic (Dec 2015)- Agent for Gout
Drug Name:Lesinurad- Zuampic (Dec 2015)- Agent for Gout
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
Moderate Cytochrome P450 2C9 (CYP2C9) Inhibitors:
Use with caution.
Sensitive CYP3A Substrates: Monitor for efficacy of the CYP3A substrate.
Indication:
ZURAMPICR (lesinurad) tablets, for oral use
Initial U.S. Approval: 2015
WARNING: RISK OF ACUTE RENAL FAILURE, MORE
COMMON WHEN USED WITHOUT A XANTHINE OXIDASE
INHIBITOR
See full prescribing information for complete boxed warning.
Acute renal failure has occurred with ZURAMPIC and was more common when
ZURAMPIC was given alone.
ZURAMPIC should be used in combination with a xanthine oxidase
inhibitor. (1.1, 5.1, 6.1)
NEW MOLECULAR ENTITY AND NEW THERAPEUTIC BIOLOGICAL
PRODUCTS APPROVED FOR 2015
Certain drugs are classified as New molecular Emtities- NME- for FDA review
Many of these products contain active moieties that have not been approved
by FDA previously, either as a single ingredient or as part of a combination
products; these products frequently provide important new therapies for the
patients.
Some drugs are characterized as NMEs for administrative purposes ,but
nonetheless contain certain active moieties in products that have been
previously approved by FDA. For example, CDER classifies biological
products submitted in an application under section 351(a) of the Public
Service Act as NME for purposes of FDA review, regardless of whether
the agency previously approved a related active moiety in a different
product.
FDAs classification of a drug as an -NME- for review purposes is distinct
from FDAs determination of whether a drug is a - New Chemical Entity or - NCE-
within the meaning of the Federal Food,Drug, and Cosmetic Act
No.45
Drug Name - Zurampic
Active Ingredient- Lesinurad
Date of approval - 12/22/2015
FDAs-approved use - To treat high blood uric acid levels associated with gout
Approved by US FDA on 12/22/2015- (Ref- FDA approved List- 2015)
Adverse Reaction:
Most common adverse reactions in 12-month controlled clinical trials
(occurring in greater than or equal to 2% of patients treated with
ZURAMPIC in combination with a xanthine oxidase inhibitor and more
frequently than on a xanthine oxidase inhibitor alone) were
headache, influenza, blood creatinine increased, and gastroesophageal
reflux disease.
Contra-Indications:
CONTRAINDICATIONS
Severe renal impairment, end stage renal disease, kidney transplant
recipients, or patients on dialysis.
Tumor lysis syndrome or Lesch-Nyhan syndrome.
WARNINGS AND PRECAUTIONS
Renal events: Adverse reactions related to renal function have occurred
after initiating ZURAMPIC.
A higher incidence was observed at the 400 mg dose, with the highest incidence
occurring with monotherapy use.
Monitor renal function at initiation and during therapy with ZURAMPIC,
particularly in patients with eCLcr below 60 mL/min, and evaluate for signs
and symptoms of acute uric acid nephropathy.
Cardiovascular events: Major adverse cardiovascular events were observed
with ZURAMPIC; a causal relationship has not been established.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
ZURAMPIC is a URAT1 inhibitor 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.
Limitations of Use:
ZURAMPIC is not recommended for the treatment of asymptomati
hyperuricemia.
ZURAMPIC should not be used as monotherapy.
DOSAGE AND ADMINISTRATION
ZURAMPIC is recommended at 200 mg once daily in combination with a
xanthine oxidase inhibitor, including allopurinol or febuxostat.
The maximum daily dose of ZURAMPIC is 200 mg.
Failure to take ZURAMPIC with a xanthine oxidase inhibitor may increase
the risk of renal adverse reactions.
ZURAMPIC tablets should be taken in the morning with food and water.
Patients should be instructed to stay well hydrated.
Assess renal function before initiating ZURAMPIC.
Do not initiateZURAMPIC if eCLcr is below 45 mL/min.
Discontinue ZURAMPIC if eCLcr persistently falls below 45 mL/min.
DOSAGE FORMS AND STRENGTHS
Tablet: 200 mg.
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Administration
Advise patients:
To take ZURAMPIC in the morning with food and water at the same time as a xanthine
oxidase inhibitor, allopurinol,or febuxostat.
Not to take ZURAMPIC alone and to discontinue ZURAMPIC if treatment with
the xanthine oxidase inhibitor medication is discontinued.
Not to take a missed dose of ZURAMPIC later in the day, to wait to take ZURAMPIC
on the next day, and not to double the dose.
To stay well hydrated (eg, 2 liters [68 oz] of liquid per day).
Renal Events Inform patients that renal events including transient increases in blood
creatinine level and acute renal failure have occurred in some patients who take
ZURAMPIC.
Advise patients that periodic monitoring of blood creatinine levels are recommended.
Gout Flares
Inform patients that gout flares may occur after initiation of ZURAMPIC and of the
importance of taking gout flare prophylaxis medication to help prevent gout flares.
Advise patients not to discontinue ZURAMPIC if a gout flare occurs during treatment
Manufactured for: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850
By: AstraZeneca AB, S-151 85 Sodertalje, Sweden Product of Ireland
ZURAMPIC is a trademark of the AstraZeneca group of companies. c AstraZeneca 2015
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Lesinurad reduces serum uric acid levels by inhibiting the function of transporter
proteins involved in uric acid reabsorption in the kidney.
Lesinurad inhibited the function of two apical transporters responsible for uric acid
reabsorption, uric acid transporter 1 (URAT1) and organic anion transporter 4 (OAT4),
with IC50 values of 7.3 and 3.7 ìM, respectively. URAT1 is responsible for the majority
of the reabsorption of filtered uric acid from the renal tubular lumen.
2. Pharmacokinetics
Following oral administration of ZURAMPIC 200 mg in healthy subjects,
the mean (% CV) Cmax and AUC for lesinurad were 6 ìg/mL (31%) and
30 ìg/hr/mL (44%),
respectively.
Cmax and AUC exposures of lesinurad increased proportionally with single doses of
ZURAMPIC from 5 to 1200 mg. Following multiple once daily dosing of ZURAMPIC,
there was no evidence of time dependent changes in pharmacokinetics and dose
proportionality was preserved.
The absolute bioavailability of lesinurad is approximately 100%. Lesinurad is rapidly absorbed after oral administration. Following administration of a single dose of a ZURAMPIC tablet in either fed or fasted state, maximum plasma concentrations (Cmax) were attained within 1 to 4 hours. Cmax and AUC exposures of lesinurad increased proportionally with single doses of ZURAMPIC from 5 to 1200 mg.
Reference ID:
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
There are no available human data on use of ZURAMPIC in pregnant women to inform
a drug-associated risk.
No teratogenicity or effects on fetal development were observed in embryo-fetal
development studies with oral administration of lesinurad to pregnant rats
and rabbits during organogenesis at doses that produced maternal exposures up to
approximately 45 and 10 times, respectively, the exposure at the maximum
recommended human dose (MRHD).
In the U.S. general population, the estimated background risk of major birth defects
and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively
2. Lactation
Risk Summary There is no information regarding the presence of ZURAMPIC in human milk, the effects on the breastfed infant, or the effects on milk production. Lesinurad is present in the milk of rats
The developmental and health benefits of breastfeeding should be considered along
with the mother’s clinical need for ZURAMPIC and any potential adverse effects on
the breastfed infant from ZURAMPIC or from the underlying maternal condition.
3.Pediatric Use
Safety and effectiveness in pediatric patients under 18 years of age have not been
established.
4. Geriatric Use
No dose adjustment is necessary in elderly patients. In a pool of clinical safety and
efficacy studies of ZURAMPIC in gout patients, 13% were 65 years and older and
2% were 75 years and older.
No overall differences between lesinurad and placebo in safety and effectiveness
were observed between these subjects and younger subjects but greater sensitivity
of some older individuals cannot be ruled out.
