+XOI
(N=516)
ZURAMPIC 200 mg
+XOI
(N=511)
Headache
4.1%
5.3%
Influenza
2.7%
5.1%
Gastroesophageal reflux disease
0.8%
2.7%
7 DRUG INTERACTIONS
7.1 CYP2C9 Inhibitors, CYP2C9 Poor Metabolizers, and CYP2C9 Inducers
Lesinurad exposure is increased when ZURAMPIC is co-administered with inhibitors of CYP2C9, and in CYP2C9 poor metabolizers. ZURAMPIC should be used with caution in patients taking moderate inhibitors of CYP2C9 (eg, fluconazole, amiodarone), and in CYP2C9 poor metabolizers [see CLINICAL PHARMACOLOGY (12.3)].
Lesinurad exposure is decreased when ZURAMPIC is co-administered with moderate inducers of CYP2C9 (eg, rifampin, carbamazepine), which may decrease the therapeutic effect of ZURAMPIC [see CLINICAL PHARMACOLOGY (12.3)].
7.2 CYP3A Substrates
In interaction studies conducted in healthy subjects with ZURAMPIC and CYP3A substrates, lesinurad reduced the plasma concentrations of sildenafil and amlodipine [see CLINICAL PHARMACOLOGY (12.3)]. Although there was not a clinically significant interaction with atorvastatin, HMG-CoA reductase inhibitors that are sensitive CYP3A substrates may be affected. The possibility of reduced efficacy of concomitant drugs that are CYP3A substrates should be considered and their efficacy (eg, blood pressure and cholesterol levels) should be monitored.
7.3 Epoxide Hydrolase Inhibitors
In vitro studies suggest that lesinurad is not an inhibitor of epoxide hydrolase; however, inhibitors of epoxide hydrolase (ie, valproic acid) may interfere with metabolism of lesinurad. ZURAMPIC should not be administered with inhibitors of epoxide hydrolase.
7.4 Hormonal Contraceptives
Hormonal contraceptives, including oral, injectable, transdermal, and implantable forms, may not be reliable when ZURAMPIC is co-administered. Females should practice additional methods of contraception and not rely on hormonal contraception alone when taking ZURAMPIC.
7.5 Aspirin
Aspirin at doses higher than 325 mg per day may decrease the efficacy of ZURAMPIC in combination with allopurinol. Aspirin at doses of 325 mg or less per day (ie, for cardiovascular protection) does not decrease the efficacy of ZURAMPIC and can be coadministered with ZURAMPIC.
8 USE IN SPECIFIC POPULATIONS
8.1 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). No adverse developmental effects were observed in a pre- and postnatal development study with administration of lesinurad to pregnant rats from organogenesis through lactation at a dose approximately 5 times the MRHD. [see Data]
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.
Data
Animal Data
In an embryo-fetal development study in pregnant rats dosed during the period of organogenesis from gestation days 6-17, lesinurad was not teratogenic and did not affect fetal development or survival at exposures up to approximately 45 times the MRHD (on an AUC basis at maternal oral doses up to 300 mg/kg/da |
