DUZALLO

Browse PDR's full list of drug information

DUZALLO

Classes

Anti-gout Combination

Administration
Oral Administration Oral Solid Formulations

Administer in the morning with food and water.
Instruct patients to stay well hydrated (e.g., drink 2 liters [68 ounces] of fluid daily).
Do not discontinue treatment if a gout flare occurs during treatment; the flare can be managed concurrently as appropriate for the individual patient.
Missed dose: Do not take a missed dose later in the day. Wait to take on the next day; do not double the dose.

Adverse Reactions
Severe

azotemia / Delayed / 0-1.0
erythema multiforme / Delayed / 0-1.0
Stevens-Johnson syndrome / Delayed / 0-1.0
exfoliative dermatitis / Delayed / 0-1.0
toxic epidermal necrolysis / Delayed / 0-1.0
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / 0-1.0
bradycardia / Rapid / 0-1.0
pericarditis / Delayed / 0-1.0
pancreatitis / Delayed / 0-1.0
GI bleeding / Delayed / 0-1.0
pancytopenia / Delayed / 0-1.0
agranulocytosis / Delayed / 0-1.0
aplastic anemia / Delayed / 0-1.0
hemolytic anemia / Delayed / 0-1.0
bronchospasm / Rapid / 0-1.0
optic neuritis / Delayed / 0-1.0
renal failure (unspecified) / Delayed / Incidence not known
hepatic necrosis / Delayed / Incidence not known
myocardial infarction / Delayed / Incidence not known
stroke / Early / Incidence not known
vasculitis / Delayed / Incidence not known

Moderate

proteinuria / Delayed / 0-1.0
hematuria / Delayed / 0-1.0
bullous rash / Early / 0-1.0
neuritis / Delayed / 0-1.0
depression / Delayed / 0-1.0
confusion / Early / 0-1.0
peripheral neuropathy / Delayed / 0-1.0
amnesia / Delayed / 0-1.0
sialadenitis / Delayed / 0-1.0
gastritis / Delayed / 0-1.0
stomatitis / Delayed / 0-1.0
lymphocytosis / Delayed / 0-1.0
eosinophilia / Delayed / 0-1.0
thrombocytopenia / Delayed / 0-1.0
leukopenia / Delayed / 0-1.0
anemia / Delayed / 0-1.0
lymphadenopathy / Delayed / 0-1.0
myopathy / Delayed / 0-1.0
peripheral vasodilation / Rapid / 0-1.0
conjunctivitis / Delayed / 0-1.0
cataracts / Delayed / 0-1.0
iritis / Delayed / 0-1.0
amblyopia / Delayed / 0-1.0
impotence (erectile dysfunction) / Delayed / 0-1.0
hyperlipidemia / Delayed / 0-1.0
hypercalcemia / Delayed / 0-1.0
nephrolithiasis / Delayed / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known
hepatomegaly / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known

Mild

headache / Early / 4.2-4.2
influenza / Delayed / 2.9-2.9
pruritus / Rapid / 0-1.0
urticaria / Rapid / 0-1.0
lichen planus-like eruption / Delayed / 0-1.0
alopecia / Delayed / 0-1.0
onycholysis / Delayed / 0-1.0
purpura / Delayed / 0-1.0
dizziness / Early / 0-1.0
tinnitus / Delayed / 0-1.0
dysgeusia / Early / 0-1.0
paresthesias / Delayed / 0-1.0
insomnia / Early / 0-1.0
drowsiness / Early / 0-1.0
dyspepsia / Early / 0-1.0
anorexia / Delayed / 0-1.0
vomiting / Early / 0-1.0
gastroesophageal reflux / Delayed / 0-1.0
abdominal pain / Early / 0-1.0
nausea / Early / 0-1.0
diarrhea / Early / 0-1.0
ecchymosis / Delayed / 0-1.0
leukocytosis / Delayed / 0-1.0
pharyngitis / Delayed / 0-1.0
rhinitis / Early / 0-1.0
arthralgia / Delayed / 0-1.0
epistaxis / Delayed / 0-1.0
gynecomastia / Delayed / 0-1.0
libido decrease / Delayed / 0-1.0
malaise / Early / 0-1.0
asthenia / Delayed / 0-1.0
hyperhidrosis / Delayed / 0-1.0
fever / Early / 0-1.0
maculopapular rash / Early / Incidence not known
rash / Early / Incidence not known

Common Brand Names

DUZALLO

Dea Class

Rx

Description

Combination of a uricosuric agent that is an urate transporter (URAT1) inhibitor with allopurinol, a xanthine oxidase inhibitor
Used for patients who have not achieved target serum uric acid levels with optimized allopurinol therapy alone
Boxed warning regarding a risk of renal failure; do not use in patients with CrCl less than 45 mL/minute

Dosage And Indications
For the treatment of hyperuricemia due to gout (gouty arthritis) in patients not achieving target serum uric acid levels with allopurinol alone. Oral dosage Adults

1 tablet (containing lesinurad 200 mg in combination with either allopurinol 200 mg or 300 mg) PO once daily in the morning with food. Use this regimen in place of the patient's previous allopurinol dose. Max: 1 tablet/day PO; each tablet contains the maximum daily lesinurad dose (200 mg/day).[62251] CLINICAL TRIALS: In clinical trials (n = 812), the use of lesinurad; allopurinol nearly doubled the number of patients who achieved target serum uric acid concentrations at 6 months compared to those receiving allopurinol alone. LIMITS OF USE: Do not use for asymptomatic hyperuricemia. Use is not recommended for patients taking daily doses of allopurinol less than 300 mg (or less than 200 mg in patients with estimated creatinine clearance [eCrCl] less than 60 mL/minute).[62251]

Dosing Considerations
Hepatic Impairment

Use is not recommended in patients with severe hepatic impairment (Child Pugh class C); lesinurad; allopurinol has not been studied in this population. No dosage adjustment is required in patients with mild or moderate hepatic impairment (Child-Pugh class A and B).

Renal Impairment

CrCl 60 mL/minute: No dosage adjustment needed.
CrCL 45 mL/minute to less than 60 mL/minute: 1 tablet (containing lesinurad 200 mg; allopurinol 200 mg) PO once daily for patients previously on a medically appropriate dose of 200 mg allopurinol. More frequent renal assessment and monitoring should occur in any patient with an estimated CrCl less than 60 mL/minute.
CrCL less than 45 mL/minute: Do not initiate treatment in these patients. If CrCL is persistently less than 45 mL/minute in a patient currently receiving lesinurad; allopurinol, then discontinue the drug.
CrCl less than 30 mL/minute: Use of this combination product is contraindicated.
 
Intermittent Hemodialysis, other types of Dialysis, or Renal Transplant
Use is contraindicated in patients with end stage renal disease, kidney transplant recipients, or patients receiving dialysis.

Drug Interactions

Abiraterone: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of abiraterone; monitor for potential reduction in efficacy. Abiraterone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Aspirin, ASA at doses higher than 325 mg per day may decrease the efficacy of lesinurad in combination with allopurinol. Aspirin at doses of 325 mg or less per day (i.e., for cardiovascular protection) does not decrease the efficacy of lesinurad and can be coadministered with lesinurad.
Acetaminophen; Butalbital: (Moderate) Barbiturates may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Barbiturates induce the CYP2C9 isoenzyme, and lesinurad is a CYP2C9 substrate.
Acetaminophen; Butalbital; Caffeine: (Moderate) Barbiturates may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Barbiturates induce the CYP2C9 isoenzyme, and lesinurad is a CYP2C9 substrate.
Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Barbiturates may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Barbiturates induce the CYP2C9 isoenzyme, and lesinurad is a CYP2C9 substrate.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with lesinurad can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If lesinurad is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Lesinurad is a weak inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Acetaminophen; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of hydrocodone as needed. If lesinurad is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Acetaminophen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of oxycodone as needed. If lesinurad is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Alfentanil: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of alfentanil; monitor for potential reduction in efficacy. Alfentanil is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Alfuzosin: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of alfuzosin; monitor for potential reduction in efficacy. Alfuzosin is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Aliskiren: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of aliskiren; monitor for potential reduction in efficacy. Aliskiren is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Aliskiren; Amlodipine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of aliskiren; monitor for potential reduction in efficacy. Aliskiren is a CYP3A substrate, and lesinurad is a weak CYP3A inducer. (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of amlodipine; monitor blood pressure closely. Amlodipine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of aliskiren; monitor for potential reduction in efficacy. Aliskiren is a CYP3A substrate, and lesinurad is a weak CYP3A inducer. (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of amlodipine; monitor blood pressure closely. Amlodipine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of aliskiren; monitor for potential reduction in efficacy. Aliskiren is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Aliskiren; Valsartan: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of aliskiren; monitor for potential reduction in efficacy. Aliskiren is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Aluminum Hydroxide: (Minor) Aluminum hydroxide decreases the oral bioavailability of allopurinol, possibly by inhibiting gastrointestinal absorption of allopurinol. Allopurinol should be administered no less than 3 hours before doses of aluminum hydroxide to avoid inhibition of allopurinol absorption.
Aluminum Hydroxide; Magnesium Carbonate: (Minor) Aluminum hydroxide decreases the oral bioavailability of allopurinol, possibly by inhibiting gastrointestinal absorption of allopurinol. Allopurinol should be administered no less than 3 hours before doses of aluminum hydroxide to avoid inhibition of allopurinol absorption.
Aluminum Hydroxide; Magnesium Hydroxide: (Minor) Aluminum hydroxide decreases the oral bioavailability of allopurinol, possibly by inhibiting gastrointestinal absorption of allopurinol. Allopurinol should be administered no less than 3 hours before doses of aluminum hydroxide to avoid inhibition of allopurinol absorption.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Minor) Aluminum hydroxide decreases the oral bioavailability of allopurinol, possibly by inhibiting gastrointestinal absorption of allopurinol. Allopurinol should be administered no less than 3 hours before doses of aluminum hydroxide to avoid inhibition of allopurinol absorption.
Aluminum Hydroxide; Magnesium Trisilicate: (Minor) Aluminum hydroxide decreases the oral bioavailability of allopurinol, possibly by inhibiting gastrointestinal absorption of allopurinol. Allopurinol should be administered no less than 3 hours before doses of aluminum hydroxide to avoid inhibition of allopurinol absorption.
Amiodarone: (Moderate) Use lesinurad and amiodarone together with caution; amiodarone may increase the systemic exposure of lesinurad. Amiodarone is a moderate inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate. In addition, lesinurad may decrease the systemic exposure and therapeutic efficacy of amiodarone; monitor for potential reduction in efficacy. Amiodarone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Amitriptyline; Chlordiazepoxide: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of chlordiazepoxide; monitor for potential reduction in efficacy. Chlordiazepoxide is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Amlodipine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of amlodipine; monitor blood pressure closely. Amlodipine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Amlodipine; Atorvastatin: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of amlodipine; monitor blood pressure closely. Amlodipine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Amlodipine; Benazepril: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of amlodipine; monitor blood pressure closely. Amlodipine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Amlodipine; Celecoxib: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of amlodipine; monitor blood pressure closely. Amlodipine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of amlodipine; monitor blood pressure closely. Amlodipine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of amlodipine; monitor blood pressure closely. Amlodipine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Amlodipine; Olmesartan: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of amlodipine; monitor blood pressure closely. Amlodipine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Amlodipine; Telmisartan: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of amlodipine; monitor blood pressure closely. Amlodipine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Amlodipine; Valsartan: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of amlodipine; monitor blood pressure closely. Amlodipine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Amobarbital: (Moderate) Barbiturates may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Barbiturates induce the CYP2C9 isoenzyme, and lesinurad is a CYP2C9 substrate.
Amoxicillin: (Minor) Use of amoxicillin with allopurinol can increase the incidence of drug-related skin rash.
Amoxicillin; Clarithromycin; Lansoprazole: (Minor) Use of amoxicillin with allopurinol can increase the incidence of drug-related skin rash.
Amoxicillin; Clarithromycin; Omeprazole: (Minor) Use of amoxicillin with allopurinol can increase the incidence of drug-related skin rash.
Amoxicillin; Clavulanic Acid: (Minor) Use of amoxicillin with allopurinol can increase the incidence of drug-related skin rash.
Ampicillin: (Minor) Use of ampicillin with allopurinol can increase the incidence of drug-related skin rash.
Ampicillin; Sulbactam: (Minor) Use of ampicillin with allopurinol can increase the incidence of drug-related skin rash.
Aprepitant, Fosaprepitant: (Moderate) Aprepitant, fosaprepitant may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Aprepitant, fosaprepitant is a mild CYP2C9 inducer, and lesinurad is a CYP2C9 substrate.
Artemether; Lumefantrine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of artemether; lumefantrine; monitor for potential reduction in efficacy. Lumefantrine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Aspirin, ASA: (Moderate) Aspirin, ASA at doses higher than 325 mg per day may decrease the efficacy of lesinurad in combination with allopurinol. Aspirin at doses of 325 mg or less per day (i.e., for cardiovascular protection) does not decrease the efficacy of lesinurad and can be coadministered with lesinurad.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Aspirin, ASA at doses higher than 325 mg per day may decrease the efficacy of lesinurad in combination with allopurinol. Aspirin at doses of 325 mg or less per day (i.e., for cardiovascular protection) does not decrease the efficacy of lesinurad and can be coadministered with lesinurad. (Moderate) Barbiturates may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Barbiturates induce the CYP2C9 isoenzyme, and lesinurad is a CYP2C9 substrate.
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Aspirin, ASA at doses higher than 325 mg per day may decrease the efficacy of lesinurad in combination with allopurinol. Aspirin at doses of 325 mg or less per day (i.e., for cardiovascular protection) does not decrease the efficacy of lesinurad and can be coadministered with lesinurad. (Moderate) Barbiturates may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Barbiturates induce the CYP2C9 isoenzyme, and lesinurad is a CYP2C9 substrate.
Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Aspirin, ASA at doses higher than 325 mg per day may decrease the efficacy of lesinurad in combination with allopurinol. Aspirin at doses of 325 mg or less per day (i.e., for cardiovascular protection) does not decrease the efficacy of lesinurad and can be coadministered with lesinurad. (Moderate) Concomitant use of dihydrocodeine with lesinurad can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If lesinurad is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Lesinurad is a weak inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Aspirin, ASA at doses higher than 325 mg per day may decrease the efficacy of lesinurad in combination with allopurinol. Aspirin at doses of 325 mg or less per day (i.e., for cardiovascular protection) does not decrease the efficacy of lesinurad and can be coadministered with lesinurad.
Aspirin, ASA; Carisoprodol: (Moderate) Aspirin, ASA at doses higher than 325 mg per day may decrease the efficacy of lesinurad in combination with allopurinol. Aspirin at doses of 325 mg or less per day (i.e., for cardiovascular protection) does not decrease the efficacy of lesinurad and can be coadministered with lesinurad.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Aspirin, ASA at doses higher than 325 mg per day may decrease the efficacy of lesinurad in combination with allopurinol. Aspirin at doses of 325 mg or less per day (i.e., for cardiovascular protection) does not decrease the efficacy of lesinurad and can be coadministered with lesinurad.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Aspirin, ASA at doses higher than 325 mg per day may decrease the efficacy of lesinurad in combination with allopurinol. Aspirin at doses of 325 mg or less per day (i.e., for cardiovascular protection) does not decrease the efficacy of lesinurad and can be coadministered with lesinurad.
Aspirin, ASA; Dipyridamole: (Moderate) Aspirin, ASA at doses higher than 325 mg per day may decrease the efficacy of lesinurad in combination with allopurinol. Aspirin at doses of 325 mg or less per day (i.e., for cardiovascular protection) does not decrease the efficacy of lesinurad and can be coadministered with lesinurad.
Aspirin, ASA; Omeprazole: (Moderate) Aspirin, ASA at doses higher than 325 mg per day may decrease the efficacy of lesinurad in combination with allopurinol. Aspirin at doses of 325 mg or less per day (i.e., for cardiovascular protection) does not decrease the efficacy of lesinurad and can be coadministered with lesinurad.
Aspirin, ASA; Oxycodone: (Moderate) Aspirin, ASA at doses higher than 325 mg per day may decrease the efficacy of lesinurad in combination with allopurinol. Aspirin at doses of 325 mg or less per day (i.e., for cardiovascular protection) does not decrease the efficacy of lesinurad and can be coadministered with lesinurad. (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of oxycodone as needed. If lesinurad is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Aspirin, ASA; Pravastatin: (Moderate) Aspirin, ASA at doses higher than 325 mg per day may decrease the efficacy of lesinurad in combination with allopurinol. Aspirin at doses of 325 mg or less per day (i.e., for cardiovascular protection) does not decrease the efficacy of lesinurad and can be coadministered with lesinurad.
Atazanavir: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of atazanavir; monitor for potential reduction in efficacy. Atazanavir is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Atazanavir; Cobicistat: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of atazanavir; monitor for potential reduction in efficacy. Atazanavir is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) Barbiturates may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Barbiturates induce the CYP2C9 isoenzyme, and lesinurad is a CYP2C9 substrate.
Avanafil: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of avanafil; monitor for potential reduction in efficacy. Avanafil is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Azathioprine: (Major) Concomitant use of allopurinol with azathioprine can result in a large increase in azathioprine activity and toxicity (e.g., bone marrow suppression, leukopenia, pancytopenia). The interaction is well-documented (i.e., multiple case reports over the course of decades) and can be potentially life-threatening. The increase in azathioprine activity is due to the ability of allopurinol to inhibit xanthine oxidase-controlled metabolism, thereby decreasing the elimination of azathioprine. When possible, this drug combination should be avoided. If avoidance of cotherapy is not possible, a reduced dosage of azathioprine (e.g., reduce to one-third to one-quarter of the original dose and close hematologic monitoring are required. Further azathioprine dosage reduction or use of an alternative therapy is recommended for patients who have low or absent thiopurine methyltransferase activity, as both the thiopurine methyltransferase and xanthine oxidase pathways are affected.
Barbiturates: (Moderate) Barbiturates may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Barbiturates induce the CYP2C9 isoenzyme, and lesinurad is a CYP2C9 substrate.
Bedaquiline: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of bedaquiline; monitor for potential reduction in efficacy. Bedaquiline is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Barbiturates may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Barbiturates induce the CYP2C9 isoenzyme, and lesinurad is a CYP2C9 substrate. (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of ergotamine; monitor for potential reduction in efficacy. Ergotamine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with lesinurad may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If concomitant use is necessary, consider increasing the benzhydrocodone dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Discontinuation of lesinurad may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. If lesinurad is discontinued, consider a benzhydrocodone dosage reduction and monitor patients for respiratory depression and sedation at frequent intervals. Benzhydrocodone is a prodrug of hydrocodone. Lesinurad is a weak inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of hydrocodone.
Boceprevir: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of boceprevir; monitor for potential reduction in efficacy. Boceprevir is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Bosentan: (Moderate) Bosentan may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Bosentan is a CYP2C9 inducer, and lesinurad is a CYP2C9 substrate.
Brentuximab vedotin: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of brentuximab vedotin; monitor for potential reduction in efficacy. Brentuximab vedotin is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of hydrocodone as needed. If lesinurad is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of hydrocodone as needed. If lesinurad is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Bupivacaine Liposomal: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of bupivacaine; monitor for potential reduction in efficacy. Bupivacaine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Bupivacaine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of bupivacaine; monitor for potential reduction in efficacy. Bupivacaine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Bupivacaine; Lidocaine: (Moderate) Concomitant use of systemic lidocaine and lesinurad may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; lesinurad induces CYP3A4. (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of bupivacaine; monitor for potential reduction in efficacy. Bupivacaine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Buprenorphine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of buprenorphine; monitor for potential reduction in efficacy. Buprenorphine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Buprenorphine; Naloxone: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of buprenorphine; monitor for potential reduction in efficacy. Buprenorphine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Buspirone: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of buspirone; monitor for potential reduction in efficacy. Buspirone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Butabarbital: (Moderate) Barbiturates may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Barbiturates induce the CYP2C9 isoenzyme, and lesinurad is a CYP2C9 substrate.
Cabotegravir; Rilpivirine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of rilpivirine; monitor for potential reduction in efficacy. Rilpivirine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Caffeine; Ergotamine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of ergotamine; monitor for potential reduction in efficacy. Ergotamine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Cannabidiol: (Moderate) Consider a dose reduction of lesinurad as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased lesinurad exposure is possible. Lesinurad is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Capecitabine: (Major) Avoid coadministration of allopurinol with capecitabine due to the risk of decreased exposure to the active metabolites of capecitabine, which may decrease capecitabine efficacy. Published literature reported that concomitant use with allopurinol may decrease conversion of capecitabine to the active metabolites FdUMP and FUTP; however, the clinical significance was not fully characterized.
Carbamazepine: (Moderate) Carbamazepine may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Carbamazepine is a CYP2C9 inducer, and lesinurad is a CYP2C9 substrate.
Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of hydrocodone as needed. If lesinurad is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of hydrocodone as needed. If lesinurad is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Chlordiazepoxide: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of chlordiazepoxide; monitor for potential reduction in efficacy. Chlordiazepoxide is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Chlordiazepoxide; Clidinium: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of chlordiazepoxide; monitor for potential reduction in efficacy. Chlordiazepoxide is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with lesinurad can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If lesinurad is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Lesinurad is a weak inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with lesinurad can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If lesinurad is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Lesinurad is a weak inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of hydrocodone as needed. If lesinurad is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Chlorpheniramine; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of hydrocodone as needed. If lesinurad is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of hydrocodone as needed. If lesinurad is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of hydrocodone as needed. If lesinurad is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Chlorpropamide: (Minor) Limited evidence suggests that concurrent allopurinol can interfere with chlorpropamide elimination. It is proposed that allopurinol interferes with renal tubular secretion of chlorpropamide. If allopurinol is added to chlorpropamide therapy, patients should be monitored for hypoglycemia.
Cilostazol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of cilostazol; monitor for potential reduction in efficacy. Cilostazol is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Clonazepam: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of clonazepam; monitor for potential reduction in efficacy. Clonazepam is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Colchicine; Probenecid: (Minor) Uricosuric agents are likely to increase the excretion of the active metabolite of allopurinol, oxypurinol. Although uricosuric agents increase the renal excretion of oxypurinol, the antihyperuricemic effects of allopurinol may be additive when administered with either probenecid or sulfinpyrazone.
Conivaptan: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of conivaptan; monitor for potential reduction in efficacy. Conivaptan is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Conjugated Estrogens; Medroxyprogesterone: (Major) Hormonal contraceptives, including combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins. This includes injectable, transdermal, and implantable forms. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females should use additional, non-hormonal methods of contraception and not rely solely on hormonal contraceptive methods when taking lesinurad.
Cyclosporine: (Moderate) Monitoring of cyclosporine levels and possible adjustment of cyclosporine dosage should be considered when these drugs are used together. Reports indicate that cyclosporine levels may be increased during concomitant treatment with allopurinol.
Dabrafenib: (Moderate) Dabrafenib may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Dabrafenib is a mild CYP2C9 inducer, and lesinurad is a CYP2C9 substrate.
Daclatasvir: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of daclatasvir; monitor for potential reduction in efficacy. Daclatasvir is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Dapsone: (Minor) The metabolism of dapsone may be accelerated when administered concurrently with lesinurad, a known inducer of CYP3A4. Coadministration is expected to decrease the plasma concentration of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis). If these drugs must be administered together, closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia.
Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Ritonavir may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Ritonavir is a CYP2C9 inducer, and lesinurad is a CYP2C9 substrate.
Delavirdine: (Moderate) Use lesinurad and delavirdine together with caution; delavirdine may increase the systemic exposure of lesinurad. Delavirdine is an inhibitor of CYP2C9 in vitro, and lesinurad is a CYP2C9 substrate.
Dextromethorphan; Quinidine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of quinidine; monitor for potential reduction in efficacy. Quinidine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Diazoxide: (Moderate) Diazoxide can cause hyperuricemia. Dosages of concomitantly administered antigout medications, including allopurinol, may require adjustment.
Dichlorphenamide: (Moderate) Use dichlorphenamide and allopurinol together with caution as both drugs can cause metabolic acidosis. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Didanosine, ddI: (Contraindicated) Concurrent use of allopurinol and didanosine, ddI is contraindicated. Coadministration may result in increased concentrations of didanosine and may increase the incidence of pancreatitis. In 14 healthy volunteers, the mean AUC of didanosine increased approximately 2-fold when given with allopurinol. This interaction was more pronounced in 2 patients with renal impairment, as coadministration resulted in elevated didanosine AUC and Cmax of 312% and 232%, respectively. The effects of allopurinol in patients with normal renal function is not known.
Dienogest; Estradiol valerate: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with lesinurad can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If lesinurad is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Lesinurad is a weak inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Dihydroergotamine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of dihydroergotamine; monitor for potential reduction in efficacy. Dihydroergotamine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of hydrocodone as needed. If lesinurad is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Disopyramide: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of disopyramide; monitor for potential reduction in efficacy. Disopyramide is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Dolutegravir; Rilpivirine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of rilpivirine; monitor for potential reduction in efficacy. Rilpivirine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Doravirine: (Minor) Concurrent administration of doravirine and lesinurad may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; lesinurad is a weak CYP3A4 inducer.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Minor) Concurrent administration of doravirine and lesinurad may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; lesinurad is a weak CYP3A4 inducer.
Dronabinol: (Moderate) Use caution if coadministration of dronabinol with lesinurad is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; lesinurad is a weak inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
Dronedarone: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of dronedarone; monitor for potential reduction in efficacy. Dronedarone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Drospirenone: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Drospirenone; Estradiol: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Drospirenone; Ethinyl Estradiol: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Efavirenz: (Moderate) Use lesinurad and efavirenz together with caution; efavirenz may increase the systemic exposure of lesinurad. Efavirenz is an inhibitor of CYP2C9 in vitro, and lesinurad is a CYP2C9 substrate.
Efavirenz; Emtricitabine; Tenofovir: (Moderate) Use lesinurad and efavirenz together with caution; efavirenz may increase the systemic exposure of lesinurad. Efavirenz is an inhibitor of CYP2C9 in vitro, and lesinurad is a CYP2C9 substrate.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Use lesinurad and efavirenz together with caution; efavirenz may increase the systemic exposure of lesinurad. Efavirenz is an inhibitor of CYP2C9 in vitro, and lesinurad is a CYP2C9 substrate.
Elagolix; Estradiol; Norethindrone acetate: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Elvitegravir: (Moderate) Elvitegravir may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Elvitegravir is a mild CYP2C9 inducer, and lesinurad is a CYP2C9 substrate. In addition, lesinurad may decrease the systemic exposure and therapeutic efficacy of elvitegravir; monitor for potential reduction in efficacy. Elvitegravir is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Elvitegravir may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Elvitegravir is a mild CYP2C9 inducer, and lesinurad is a CYP2C9 substrate. In addition, lesinurad may decrease the systemic exposure and therapeutic efficacy of elvitegravir; monitor for potential reduction in efficacy. Elvitegravir is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Elvitegravir may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Elvitegravir is a mild CYP2C9 inducer, and lesinurad is a CYP2C9 substrate. In addition, lesinurad may decrease the systemic exposure and therapeutic efficacy of elvitegravir; monitor for potential reduction in efficacy. Elvitegravir is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of rilpivirine; monitor for potential reduction in efficacy. Rilpivirine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of rilpivirine; monitor for potential reduction in efficacy. Rilpivirine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Enalapril; Felodipine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of felodipine; monitor for potential reduction in efficacy. Felodipine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Enzalutamide: (Moderate) Monitor for decreased efficacy of lesinurad if coadministration with enzalutamide is necessary. Lesinurad is a CYP2C9 substrate and enzalutamide is a moderate CYP2C9 inducer. Coadministration with another CYP2C9 inducer deceased lesinurad exposure by 38%.
Eplerenone: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of eplerenone; monitor for potential reduction in efficacy. Eplerenone is a sensitive CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Ergotamine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of ergotamine; monitor for potential reduction in efficacy. Ergotamine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Estazolam: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of estazolam; monitor for potential reduction in efficacy. Estazolam is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Estradiol Cypionate; Medroxyprogesterone: (Major) Hormonal contraceptives, including combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins. This includes injectable, transdermal, and implantable forms. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females should use additional, non-hormonal methods of contraception and not rely solely on hormonal contraceptive methods when taking lesinurad.
Estradiol; Levonorgestrel: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Estradiol; Norethindrone: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Estradiol; Norgestimate: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Estradiol; Progesterone: (Major) Hormonal contraceptives, including combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins. This includes injectable, transdermal, and implantable forms. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females should use additional, non-hormonal methods of contraception and not rely solely on hormonal contraceptive methods when taking lesinurad.
Ethinyl Estradiol: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Ethinyl Estradiol; Desogestrel: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Ethinyl Estradiol; Ethynodiol Diacetate: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Ethinyl Estradiol; Etonogestrel: (Major) Hormonal contraceptives, including combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins. This includes injectable, transdermal, and implantable forms. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females should use additional, non-hormonal methods of contraception and not rely solely on hormonal contraceptive methods when taking lesinurad. (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Ethinyl Estradiol; Levonorgestrel: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Ethinyl Estradiol; Norelgestromin: (Major) Hormonal contraceptives, including combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins. This includes injectable, transdermal, and implantable forms. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females should use additional, non-hormonal methods of contraception and not rely solely on hormonal contraceptive methods when taking lesinurad. (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Ethinyl Estradiol; Norethindrone Acetate: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods wh

en taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Ethinyl Estradiol; Norethindrone: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Ethinyl Estradiol; Norgestimate: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Ethinyl Estradiol; Norgestrel: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Etonogestrel: (Major) Hormonal contraceptives, including combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins. This includes injectable, transdermal, and implantable forms. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females should use additional, non-hormonal methods of contraception and not rely solely on hormonal contraceptive methods when taking lesinurad.
Etravirine: (Moderate) Use lesinurad and etravirine together with caution; etravirine may increase the systemic exposure of lesinurad. Etravirine is an inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate.
Felodipine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of felodipine; monitor for potential reduction in efficacy. Felodipine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Fentanyl: (Moderate) Consider an increased dose of fentanyl and monitor for evidence of opioid withdrawal if concurrent use of lesinurad is necessary. If lesinurad is discontinued, consider reducing the fentanyl dosage and monitor for evidence of respiratory depression. Coadministration of a CYP3A4 inducer like lesinurad with fentanyl, a CYP3A4 substrate, may decrease exposure to fentanyl resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to fentanyl. Fentanyl plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Floxuridine: (Minor) Allopurinol can interfere in the activation of fluorouracil, 5-FU, and thus impair its activity. Because floxuridine is metabolized to fluorouracil, a similar interaction can occur with floxuridine. Theoretically, this may provide protection to host tissues and preserve anti-tumor activity since host tissues, but not all tumors, rely on the effected activation pathway. However, the reduction of 5-FU toxicity, specifically mucositis, by allopurinol has been inconsistent in clinical trials. In some animal models, allopurinol has decreased the effectiveness of 5-FU.
Fluconazole: (Moderate) Use lesinurad and fluconazole together with caution; fluconazole may increase the systemic exposure of lesinurad. Fluconazole is a moderate inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate. The enzyme-inhibiting effect of fluconazole persists 4 to 5 days after discontinuation of fluconazole treatment due to its long half-life.
Fluorouracil, 5-FU: (Moderate) Use lesinurad and fluorouracil, 5-FU together with caution; fluorouracil may increase the systemic exposure of lesinurad. Fluorouracil is an inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate. (Minor) Allopurinol may interfere with the activation of fluorouracil, 5-FU, and decrease the effectiveness of 5-FU.
Fluoxetine: (Moderate) Use lesinurad and fluoxetine together with caution; fluoxetine may increase the systemic exposure of lesinurad. Fluoxetine is a mild inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate.
Fluoxetine; Olanzapine: (Moderate) Use lesinurad and fluoxetine together with caution; fluoxetine may increase the systemic exposure of lesinurad. Fluoxetine is a mild inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate.
Flurazepam: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of flurazepam; monitor for potential reduction in efficacy. Flurazepam is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Fluvastatin: (Moderate) Use lesinurad and fluvastatin together with caution; fluvastatin may increase the systemic exposure of lesinurad. Fluvastatin is a mild inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate.
Fluvoxamine: (Moderate) Use lesinurad and fluvoxamine together with caution; fluvoxamine may increase the systemic exposure of lesinurad. Fluvoxamine is a mild inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate.
Fosphenytoin: (Moderate) Phenytoin and fosphenytoin may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Phenytoin and fosphenytoin are CYP2C9 inducers, and lesinurad is a CYP2C9 substrate.
Gemfibrozil: (Moderate) Use lesinurad and gemfibrozil together with caution; gemfibrozil may increase the systemic exposure of lesinurad. Gemfibrozil is a mild inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate.
Granisetron: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of granisetron; monitor for potential reduction in efficacy. Granisetron is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Guaifenesin; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of hydrocodone as needed. If lesinurad is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of hydrocodone as needed. If lesinurad is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Halofantrine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of halofantrine; monitor for potential reduction in efficacy. Halofantrine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Homatropine; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of hydrocodone as needed. If lesinurad is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of hydrocodone as needed. If lesinurad is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Hydrocodone; Ibuprofen: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of hydrocodone as needed. If lesinurad is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Hydrocodone; Phenylephrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of hydrocodone as needed. If lesinurad is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of hydrocodone as needed. If lesinurad is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of hydrocodone as needed. If lesinurad is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of hydrocodone as needed. If lesinurad is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Ibrutinib: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of ibrutinib; monitor for potential reduction in efficacy. Ibrutinib is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Ibuprofen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of oxycodone as needed. If lesinurad is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Idelalisib: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of idelalisib; monitor for potential reduction in efficacy. Idelalisib is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Imatinib: (Moderate) Use lesinurad and imatinib, STI-571 together with caution; imatinib may increase the systemic exposure of lesinurad. Imitinab is an inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate.
Indinavir: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of indinavir; monitor for potential reduction in efficacy. Indinavir is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Rifampin may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Rifampin is a CYP2C9 inducer, and lesinurad is a CYP2C9 substrate. (Minor) Because pyrazinamide, PZA can increase serum uric acid levels and precipitate gouty attacks, the dosages of antigout agents, including allopurinol, may need to be adjusted.
Isoniazid, INH; Rifampin: (Moderate) Rifampin may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Rifampin is a CYP2C9 inducer, and lesinurad is a CYP2C9 substrate.
Isradipine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of isradipine; monitor for potential reduction in efficacy. Isradipine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Ivabradine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of ivabradine; monitor for potential reduction in efficacy. Ivabradine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Ixabepilone: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of ixabepilone; monitor for potential reduction in efficacy. Ixabepilone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Ketoconazole: (Moderate) Use lesinurad and ketoconazole together with caution; ketoconazole may increase the systemic exposure of lesinurad. Ketoconazole is a mild inhibitor of CYP2C9 in vitro and lesinurad is a CYP2C9 substrate.
Leflunomide: (Moderate) Use lesinurad and leflunomide together with caution; leflunomide may increase the systemic exposure of lesinurad. Leflunomide is an inhibitor of CYP2C9 in vitro, and lesinurad is a CYP2C9 substrate.
Leuprolide; Norethindrone: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Levamlodipine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of amlodipine; monitor blood pressure closely. Amlodipine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Levomilnacipran: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of levomilnacipran; monitor for potential reduction in efficacy. Levomilnacipran is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Levonorgestrel: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Lidocaine: (Moderate) Concomitant use of systemic lidocaine and lesinurad may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; lesinurad induces CYP3A4.
Lidocaine; Prilocaine: (Moderate) Concomitant use of systemic lidocaine and lesinurad may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; lesinurad induces CYP3A4.
Lomitapide: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of lomitapide; monitor for potential reduction in efficacy. Lomitapide is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Loperamide: (Moderate) The plasma concentration and efficacy of loperamide may be reduced when administered concurrently with lesinurad. Loperamide is metabolized by the hepatic enzyme CYP3A4; lesinurad is a mild inducer of this enzyme.
Loperamide; Simethicone: (Moderate) The plasma concentration and efficacy of loperamide may be reduced when administered concurrently with lesinurad. Loperamide is metabolized by the hepatic enzyme CYP3A4; lesinurad is a mild inducer of this enzyme.
Lopinavir; Ritonavir: (Moderate) Ritonavir may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Ritonavir is a CYP2C9 inducer, and lesinurad is a CYP2C9 substrate.
Lumateperone: (Major) Avoid coadministration of lumateperone and lesinurad as concurrent use may decrease lumateperone exposure which may reduce efficacy. Lumateperone is a CYP3A4 substrate; lesinurad is a weak CYP3A4 inducer.
Lurasidone: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of lurasidone; monitor for potential reduction in efficacy. Lurasidone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Macitentan: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of macitentan; monitor for potential reduction in efficacy. Macitentan is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Maraviroc: (Minor) Use caution if coadministration of maraviroc with lesinurad is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and lesinurad is a weak CYP3A4 inducer. Monitor for a decrease in efficacy with concomitant use.
Medroxyprogesterone: (Major) Hormonal contraceptives, including combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins. This includes injectable, transdermal, and implantable forms. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females should use additional, non-hormonal methods of contraception and not rely solely on hormonal contraceptive methods when taking lesinurad.
Mephobarbital: (Moderate) Barbiturates may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Barbiturates induce the CYP2C9 isoenzyme, and lesinurad is a CYP2C9 substrate.
Mercaptopurine, 6-MP: (Major) The concomitant use of mercaptopurine and allopurinol may result in increased mercaptopurine toxicity (e.g., bone marrow suppression, nausea, and vomiting). If these drugs are used together, reduce the mercaptopurine dose to one-third to one-quarter of the usual dose to avoid severe toxicity. Allopurinol inhibits xanathine oxidase; mercaptopurine is inactivated via the xanathine oxidase enzyme.
Mestranol; Norethindrone: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Methohexital: (Moderate) Barbiturates may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Barbiturates induce the CYP2C9 isoenzyme, and lesinurad is a CYP2C9 substrate.
Methotrexate: (Minor) In vitro studies have shown that allopurinol administered one hour prior to methotrexate may decrease the therapeutic effects of methotrexate.
Methoxsalen: (Minor) Preclinical data suggests that allopurinol may decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Midazolam: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of midazolam; monitor for potential reduction in efficacy. Midazolam is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Mifepristone: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of mifepristone; monitor for potential reduction in efficacy. Mifepristone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with lesinurad is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer.
Nefazodone: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of nefazodone; monitor for potential reduction in efficacy. Nefazodone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of netupitant; palonosetron; monitor for potential reduction in efficacy. Netupitant is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Nifedipine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of nifedipine; monitor for potential reduction in efficacy. Nifedipine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Nimodipine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of nimodipine; monitor for potential reduction in efficacy. Nimodipine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with lesinurad due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and lesinurad is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Non-oral combination contraceptives: (Major) Hormonal contraceptives, including combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins. This includes injectable, transdermal, and implantable forms. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females should use additional, non-hormonal methods of contraception and not rely solely on hormonal contraceptive methods when taking lesinurad.
Norethindrone: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Norgestrel: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Ritonavir may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Ritonavir is a CYP2C9 inducer, and lesinurad is a CYP2C9 substrate.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of rifabutin; monitor for potential reduction in efficacy. Rifabutin is a CYP3A substrate, and lesinurad is a weak CYP3A inducer. (Minor) Use of amoxicillin with allopurinol can increase the incidence of drug-related skin rash.
Oral Contraceptives: (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Oritavancin: (Moderate) Use lesinurad and oritavancin together with caution; oritavancin may increase the systemic exposure of lesinurad. Oritavancin is a mild inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate.
Oxybutynin: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of oxybutynin; monitor for potential reduction in efficacy. Oxybutynin is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of oxycodone as needed. If lesinurad is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Paricalcitol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of paricalcitol; monitor for potential reduction in efficacy. Paricalcitol is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Pegloticase: (Major) Allopurinol may potentially blunt the rise of serum uric acid levels in patients taking pegloticase. Since patients who have lost therapeutic response to pegloticase are at higher risk of developing anaphylaxis and infusion reactions, oral urate-lowering therapy should be discontinued prior to pegloticase initiation and withheld during the course of treatment.
Pentobarbital: (Moderate) Barbiturates may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Barbiturates induce the CYP2C9 isoenzyme, and lesinurad is a CYP2C9 substrate.
Perindopril; Amlodipine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of amlodipine; monitor blood pressure closely. Amlodipine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with allopurinol. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
Phenobarbital: (Moderate) Barbiturates may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Barbiturates induce the CYP2C9 isoenzyme, and lesinurad is a CYP2C9 substrate.
Phenytoin: (Moderate) Phenytoin and fosphenytoin may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Phenytoin and fosphenytoin are CYP2C9 inducers, and lesinurad is a CYP2C9 substrate.
Pirfenidone: (Moderate) Use lesinurad and pirfenidone together with caution; pirfenidone may increase the systemic exposure of lesinurad. Pirfenidone is a mild inhibitor of CYP2C9 in vitro, and lesinurad is a CYP2C9 substrate.
Praziquantel: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of praziquantel; monitor for potential reduction in efficacy. In vitro and drug interaction studies suggest praziquantel may be a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Prednisolone: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of prednisolone; monitor for potential reduction in efficacy. Prednisolone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Primidone: (Moderate) Barbiturates may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Barbiturates induce the CYP2C9 isoenzyme, and lesinurad is a CYP2C9 substrate.
Probenecid: (Minor) Uricosuric agents are likely to increase the excretion of the active metabolite of allopurinol, oxypurinol. Although uricosuric agents increase the renal excretion of oxypurinol, the antihyperuricemic effects of allopurinol may be additive when administered with either probenecid or sulfinpyrazone.
Progesterone: (Major) Hormonal contraceptives, including combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins. This includes injectable, transdermal, and implantable forms. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females should use additional, non-hormonal methods of contraception and not rely solely on hormonal contraceptive methods when taking lesinurad.
Pyrazinamide, PZA: (Minor) Because pyrazinamide, PZA can increase serum uric acid levels and precipitate gouty attacks, the dosages of antigout agents, including allopurinol, may need to be adjusted.
Quetiapine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of quetiapine; monitor for potential reduction in efficacy. Quetiapine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Quinidine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of quinidine; monitor for potential reduction in efficacy. Quinidine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Rifabutin: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of rifabutin; monitor for potential reduction in efficacy. Rifabutin is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Rifampin: (Moderate) Rifampin may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Rifampin is a CYP2C9 inducer, and lesinurad is a CYP2C9 substrate.
Rilpivirine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of rilpivirine; monitor for potential reduction in efficacy. Rilpivirine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and allopurinol. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Ritonavir: (Moderate) Ritonavir may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Ritonavir is a CYP2C9 inducer, and lesinurad is a CYP2C9 substrate.
Rolapitant: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of rolapitant; monitor for potential reduction in efficacy. Rolapitant is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Secobarbital: (Moderate) Barbiturates may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Barbiturates induce the CYP2C9 isoenzyme, and lesinurad is a CYP2C9 substrate.
Segesterone Acetate; Ethinyl Estradiol: (Major) Hormonal contraceptives, including combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins. This includes injectable, transdermal, and implantable forms. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females should use additional, non-hormonal methods of contraception and not rely solely on hormonal contraceptive methods when taking lesinurad. (Major) Lesinurad induces CYP3A4, which may reduce the concentrations of estrogen and progestin hormones. Hormonal contraceptives may not be reliable when coadministered with lesinurad. Females taking hormonal-based birth control should use additional non-hormonal methods and not rely solely on hormonal contraceptive methods when taking lesinurad. Hormonal contraceptives include combination oral contraceptives, non-oral combination contraceptives, and contraceptives containing only progestins and includes oral, injectable, transdermal, vaginal inserts, and implantable forms of hormonal birth control. Lesinurad may also reduce the effectiveness of other estrogens or progestins. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on lesinurad, with adjustments made based on clinical efficacy.
Sildenafil: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of sildenafil; monitor for potential reduction in efficacy. Sildenafil is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Silodosin: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of silodosin; monitor for potential reduction in efficacy. Silodosin is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Sofosbuvir; Velpatasvir: (Major) Use caution when administering velpatasvir with lesinurad. Taking these drugs together may decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; lesinurad is a weak inducer of CYP3A4.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Use caution when administering velpatasvir with lesinurad. Taking these drugs together may decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; lesinurad is a weak inducer of CYP3A4.
Solifenacin: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of solifenacin; monitor for potential reduction in efficacy. Solifenacin is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Sonidegib: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of sonidegib; monitor for potential reduction in efficacy. Sonidegib is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
St. John's Wort, Hypericum perforatum: (Moderate) St. John's wort may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. St. John's wort is a CYP2C9 inducer, and lesinurad is a CYP2C9 substrate. The amount of individual constituents in various products may alter the inhibiting or inducing effects, making drugs interactions unpredictable.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if lesinurad must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with lesinurad is necessary; consider increasing the dose of sufentanil injection as needed. If lesinurad is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and lesinurad is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Use lesinurad and sulfamethoxazole together with caution; sulfamethoxazole may increase the systemic exposure of lesinurad. Sulfamethoxazole is an inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate.
Sulfinpyrazone: (Moderate) Use lesinurad and sulfinpyrazone together with caution; sulfinpyrazone may increase the systemic exposure of lesinurad. Sulfinpyrazone is an inhibitor of CYP2C9 in vitro, and lesinurad is a CYP2C9 substrate. (Minor) Uricosuric agents are likely to increase the excretion of the active metabolite of allopurinol, oxypurinol. Although uricosuric agents increase the renal excretion of oxypurinol, the antihyperuricemic effects of allopurinol may be additive when administered with either probenecid or sulfinpyrazone.
Tacrolimus: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of tacrolimus; monitor for potential reduction in efficacy. Tacrolimus is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Tadalafil: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of tadalafil; monitor for potential reduction in efficacy. Tadalafil is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Telithromycin: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of telithromycin; monitor for potential reduction in efficacy. Telithromycin is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Theophylline, Aminophylline: (Minor) Allopurinol in large doses can decrease aminophylline clearance. It appears that the significance of this drug interaction depends on the dose of allopurinol. (Minor) Allopurinol in large doses can decrease theophylline clearance. It appears that the significance of this drug interaction depends on the dose of allopurinol.
Thiazide diuretics: (Moderate) The occurrence of certain hypersensitivity reactions may be increased in patients with renal impairment who receive allopurinol and thiazide diuretics in combination. The precise mechanism for such events is unclear but likely immune-mediated and may be related to an effect of oxypurinol; elevated oxypurinol concentrations appear to be associated with hypersensitivity reactions; decreased clearance of this metabolite may occur with renal impairment and with the concurrent use of thiazide diuretics. Severe skin reactions include exfoliative dermatitis, toxic epidermal necrolysis and Steven's Johnson syndrome; some reactions have been fatal. In addition, thiazide diuretics, like hydrochlorothiazide, can cause hyperuricemia. Since thiazides reduce the clearance of uric acid, patients with gout or hyperuricemia may have exacerbations of their disease.
Thiopental: (Moderate) Barbiturates may decrease the systemic exposure and therapeutic effect of lesinurad; monitor for potential reduction in efficacy. Barbiturates induce the CYP2C9 isoenzyme, and lesinurad is a CYP2C9 substrate.
Tiagabine: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of tiagabine; monitor for potential reduction in efficacy. Tiagabine is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Tinidazole: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of tinidazole; monitor for potential reduction in efficacy. Tinidazole is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Tolvaptan: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of tolvaptan; monitor for potential reduction in efficacy. Tolvaptan is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Triazolam: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of triazolam; monitor for potential reduction in efficacy. Triazolam is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Ubrogepant: (Major) Increase the initial and second dose of ubrogepant to 100 mg if coadministered with lesinurad as concurrent use may decrease ubrogepant exposure and reduce its efficacy. Ubrogepant is a CYP3A4 substrate; lesinurad is a weak CYP3A4 inducer.
Ulipristal: (Moderate) Lesinurad is a weak CYP3A4 inducer. As ulipristal is metabolized by CYP3A4, its effectiveness may be diminished when given with lesinurad. Strong CYP3A4 inducers should be avoided with ulipristal. Monitor the patient for the desired clinical effect if ulipristal must be administered to a patient taking lesinurad.
Uricosuric Agents: (Minor) Uricosuric agents are likely to increase the excretion of the active metabolite of allopurinol, oxypurinol. Although uricosuric agents increase the renal excretion of oxypurinol, the antihyperuricemic effects of allopurinol may be additive when administered with either probenecid or sulfinpyrazone.
Valproic Acid, Divalproex Sodium: (Major) Lesinurad should not be administered with valproic acid, divalproex sodium. In vitro studies suggest inhibitors of epoxide hydrolase, such as valproic acid, may interfere with the metabolism of lesinurad.
Vorapaxar: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of vorapaxar; monitor for potential reduction in efficacy. Vorapaxar is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Voriconazole: (Moderate) Use lesinurad and voriconazole together with caution; voriconazole may increase the systemic exposure of lesinurad. Voriconazole is an inhibitor of CYP2C9 in vitro, and lesinurad is a CYP2C9 substrate.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with lesinurad is necessary as concurrent use may decrease the exposure of warfarin leading to reduced efficacy. Lesinurad is a weak CYP3A4 inducer and the R-enantiomer of warfarin is a CYP3A4 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance. (Minor) Allopurinol may interfere with the metabolism of warfarin. The INR should be monitored carefully in patients receiving oral anticoagulants when allopurinol therapy is added.
Zafirlukast: (Moderate) Use lesinurad and zafirlukast together with caution; zafirlukast may increase the systemic exposure of lesinurad. Zafirlukast is an inhibitor of CYP2C9 in vitro, and lesinurad is a CYP2C9 substrate.
Ziprasidone: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of ziprasidone; monitor for potential reduction in efficacy. Ziprasidone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.

How Supplied

Lesinurad, Allopurinol Oral Tab: 200-200mg, 200-300mg

Maximum Dosage
Adults

Lesinurad 200 mg/day PO; allopurinol 300 mg/day PO.

Geriatric

Lesinurad 200 mg/day PO; allopurinol 300 mg/day PO.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Mechanism Of Action

Lesinurad and allopurinol act together, by different mechanisms, to lower serum uric acid concentrations.
Lesinurad: Lesinurad reduces serum uric acid concentrations by inhibiting the function of 2 transporter proteins involved in uric acid reabsorption in the kidney. Lesinurad inhibits the function of uric acid transporter 1 (URAT1), which is responsible for the majority of the reabsorption of filtered uric acid from the renal tubular lumen, and also inhibits organic anion transporter 4 (OAT4), a protein associated with diuretic-induced hyperuricemia. Following single and multiple oral doses of lesinurad to gout patients, dose-dependent decreases in serum uric acid levels and increases in urinary uric acid excretion were observed.
Allopurinol: Unlike uricosuric agents, which increase the urinary excretion of uric acid, allopurinol interferes with the catabolism of purines. It reduces the production of uric acid by inhibiting the biochemical reactions immediately preceding uric acid formation. Concentrations of uric acid in the blood and urine are thereby lowered. Allopurinol inhibits the enzyme xanthine oxidase, which blocks the metabolism of hypoxanthine to xanthine and of xanthine to uric acid. Allopurinol is metabolized to oxipurinol, which also is an inhibitor of xanthine oxidase. Oxypurinol, an allopurinol metabolite, also inhibits xanthine oxidase. Allopurinol also facilitates the incorporation of hypoxanthine and xanthine into DNA and RNA, resulting in further reductions of serum uric acid concentrations. Although hypoxanthine and xanthine serum concentrations increase, their renal clearance is at least 10 times that of uric acid. The serum concentration of hypoxanthine plus xanthine in patients receiving allopurinol is usually in the range of 0.3 to 0.4 mg/dL compared to normal level of approximately 0.15 mg/dL. Precipitation is expected to occur with concentrations above 7 mg/dL. A secondary result of decreased renal tubular transport of uric acid is increased nephron reabsorption of calcium ions.

Pharmacokinetics

Lesinurad; allopurinol is administered orally.
Lesinurad: Lesinurad is highly bound to plasma proteins. The steady state volume of distribution is approximately 20 L following an intravenous dose. Lesinurad does not accumulate following multiple doses. Lesinurad is metabolized via oxidation mainly by the cytochrome P450 2C9 isoenzyme (CYP2C9). Plasma exposure of metabolites is minimal (less than 10% of unchanged lesinurad). Metabolites are not known to contribute to the uric acid lowering effects of lesinurad. The total body clearance is 6 L/hour. Within 7 days following a single radiolabeled dose of lesinurad, 63% of the dose is recovered in the urine and 32% in the feces. Most of the radioactivity recovered in the urine occurred in the first 24 hours. Unchanged lesinurad in urine accounted for approximately 30% of the dose. The elimination half-life is approximately 5 hours.
Allopurinol: Allopurinol distributes throughout the body tissues and into breast milk. Allopurinol is rapidly metabolized by hepatic oxidation to the active compound oxypurinol (alloxanthine). The rapid conversion of allopurinol to oxypurinol was not significantly different after repeated allopurinol dosing. The plasma half-life of allopurinol is 1 to 2 hours. The oxypurinol half-life is approximately 24 hours. Allopurinol is cleared essentially by glomerular filtration, but oxypurinol is reabsorbed in the kidney tubules in a manner similar to the reabsorption of uric acid. Approximately 20% of the drug is excreted in the feces. The remainder is primarily metabolized to oxypurinol.
 
Affected cytochrome P450 (CYP450) isoenzymes, and other enzymes and drug transporters: CYP2C9, CYP3A4, epoxide hydrolase
Lesinurad is a substrate for CYP2C9, and medications which potently inhibit CYP2C9 should be used with caution in combination with lesinurad due to the potential for increased concentrations. Patients who are CYP2C9 poor metabolizers also exhibit increased exposure to the drug. Lesinurad also is a weak inducer of CYP3A4. In vitro studies suggest that lesinurad is not an inhibitor of epoxide hydrolase; however, inhibitors of epoxide hydrolase may interfere with metabolism of lesinurad. Do not administer lesinurad with inhibitors of epoxide hydrolase.

Oral Route

Lesinurad and allopurinol are both rapidly absorbed after oral administration. Following a single lesinurad dose administered in a fed or fasted state, maximal concentration (Cmax) was attained within 1 to 4 hours. Peak plasma concentrations occur at 1.5 hours for allopurinol and 4.5 hours for oxypurinol. Administration with a high-fat meal decreases Cmax of lesinurad by up to 18% and the Cmax of allopurinol by 46%. The effect of food is not considered to be clinically meaningful. Lesinurad; allopurinol was administered with food in clinical trials.

Pregnancy And Lactation
Pregnancy

There are no available human data on the use of lesinurad; allopurinol or lesinurad during pregnancy to inform a drug-associated risk of adverse developmental outcomes. Limited data on allopurinol in pregnant women do not demonstrate a clear pattern or increase in frequency of adverse developmental outcomes. Animal reproductive studies were not conducted on lesinurad; allopurinol; however, studies were conducted with the individual components. 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 post-natal development study with the oral administration of lesinurad to pregnant rats from organogenesis through lactation at a dose approximately 5 times the MRHD. No teratogenic effects were observed in embryo-fetal development studies with orally administered allopurinol to pregnant rats or rabbits during organogenesis at doses approximately 6 times the MRHD. Allopurinol crossed the placental barrier following oral administration to pregnant pigs and was detected in fetal plasma. Animal reproductive studies are not always predictive of human response.

Use lesinurad; allopurinol with caution during breast-feeding. There is no information regarding the presence of lesinurad; allopurinol or lesinurad in human milk, the effects on the breast-fed infant, or the effects on milk production. Based on a single case report, allopurinol and its active metabolite, oxypurinol, were detected in the milk of a mother at 5 weeks postpartum. There were no adverse effects on the breast-fed infant or milk production; however, the effect of allopurinol on a nursing infant is unknown. Lesinurad is present in the milk of rats. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for lesinurad; allopurinol and any potential adverse effects on the breastfed infant from lesinurad or the underlying maternal condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.