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  • CLASSES

    Anti-Gout Agents

    DEA CLASS

    Rx

    DESCRIPTION

    Uricosuric agent that is a urate transporter (URAT1) inhibitor
    Used for hyperuricemia due to gout, must be used in combination with a xanthine oxidase inhibitor
    Boxed warning regarding a risk of renal failure; do not use in patients with CrCl less than 45 mL/minute

    COMMON BRAND NAMES

    ZURAMPIC

    HOW SUPPLIED

    ZURAMPIC Oral Tab: 200mg

    DOSAGE & INDICATIONS

    For the adjunct treatment of hyperuricemia due to gout (gouty arthritis) in patients not achieving target serum uric acid levels with a xanthine oxidase inhibitor alone.
    Oral dosage
    Adults

    200 mg PO once daily in the morning, at the same time as the morning dose of xanthine oxidase inhibitor. If treatment with the xanthine oxidase inhibitor is interrupted, lesinurad should also be interrupted. LIMITS OF USE: Do not use as monotherapy. 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).

    MAXIMUM DOSAGE

    Adults

    200 mg/day PO.

    Geriatric

    200 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.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Use is not recommended in patients with severe hepatic impairment (Child Pugh class C); lesinurad 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/min: No dosage adjustment is required. Periodically assess renal function.
    CrCL 45 mL/min to < 60 mL/min: No dosage adjustment required. More frequent renal assessment and monitoring should occur in any patient with an estimated CrCl < 60 mL/min.
    CrCL < 45 mL/min: Do not initiate treatment in these patients. If CrCL is persistently < 45 mL/min in a patient currently receiving lesinurad, then discontinue the drug.
    CrCl < 30 mL/min: Use 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.

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    MUST be co-administered with a xanthine oxidase inhibitor, such as allopurinol or febuxostat. 
    Administer in the morning with food at water, at the same time as the morning dose of xanthine oxidase inhibitor. 
    If treatment with the xanthine oxidase inhibitor is interrupted, lesinurad should also be interrupted. Failure to follow these instructions may increase the risk of adverse renal events.
    Patients should be instructed to stay well hydrated (e.g., 2 liters [68 ounces] of liquid per day).
    Do not discontinue lesinurad if a gout flare occurs during treatment; the flare can be managed concurrently as appropriate for the individual patient.

    STORAGE

    ZURAMPIC:
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Lesinurad is not recommended for the treatment of asymptomatic hyperuricemia, and should only be added when target serum uric acid concentrations are not achieved on a medically appropriate dose of xanthine oxidase inhibitor alone.
     
    Use of lesinurad is not recommended for patients taking allopurinol doses less than 300 mg/day or, in patients with an estimated CrCl < 60 mL/minute, allopurinol doses less than 200 mg/day.
     
    Gout flares may occur after initiation of urate lowering therapy, such as lesinurad, due to changing serum uric acid concentrations resulting in mobilization of urate from tissue deposits. Clinical practice guidelines recommend gout flare prophylaxis when starting lesinurad. If a gout flare occurs during lesinurad treatment, lesinurad does not need to be discontinued. Manage the flare concurrently, as appropriate for the individual patient.

    Dialysis, kidney transplant, renal disease, renal failure, renal impairment

    Lesinurad is contraindicated in patients with severe renal impairment, end stage renal disease (kidney failure), kidney transplant recipients, and patients on dialysis. Do not initiate in patients with an estimated creatinine clearance (CrCl) less than 45 mL/minute. Renal dysfunction, including acute renal failure, has occurred with lesinurad and was more common when lesinurad was given alone; therefore the drug should be used in combination with a xanthine oxidase inhibitor (e.g., allopurinol). During clinical trials, use of lesinurad and xanthine oxidase inhibitor combination therapy was associated with an increased incidence of serum creatinine (SCr) elevations, most of which were reversible. A higher incidence of SCr elevations and renal-related adverse effects, including acute renal failure, occurred with lesinurad doses of 400 mg (the FDA-approved dose is 200 mg/day), and when lesinurad was given as monotherapy. Instruct patients to stay well hydrated (e.g., 2 liters [68 ounces] of fluids per day). Monitor renal function at baseline and periodically throughout lesinurad therapy. More frequent monitoring should occur in patients with an estimated CrCl less than 60 mL/minute or in those with SCr elevations 1.5 to 2 times the pre-treatment value. Interrupt lesinurad therapy if SCr is elevated to more than 2 times the pre-treatment value. Discontinue lesinurad therapy if the estimated CrCl is persistently less than 45 mL/minute. If symptoms that may indicate acute uric acid nephropathy (i.e., flank pain, nausea, vomiting) present, interrupt treatment and measure SCr promptly. Lesinurad should not be restarted without an alternative explanation for the SCr abnormalities.

    Hepatic disease

    Lesinurad has not been studied in patients with severe hepatic disease/impairment and is therefore not recommended in this population.

    Lesch-Nyhan syndrome, organ transplant, secondary hyperuricemia, tumor lysis syndrome (TLS)

    Lesinurad is contraindicated in patients with tumor lysis syndrome (TLS) or Lesch-Nyhan syndrome, where the rate of uric acid formation is greatly increased. No studies have been conducted in patients with secondary hyperuricemia, including organ transplant recipients.

    Pregnancy

    There are no available human data on the use of lesinurad during pregnancy. 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).

    Breast-feeding

    There is no information regarding the presence of lesinurad in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for lesinurad and any potential adverse effects on the breastfed infant from lesinurad or the underlying maternal condition.

    ADVERSE REACTIONS

    Severe

    renal failure (unspecified) / Delayed / 1.2-1.2
    myocardial infarction / Delayed / Incidence not known
    stroke / Early / Incidence not known

    Moderate

    nephrolithiasis / Delayed / 0.6-0.6

    Mild

    headache / Early / 5.3-5.3
    influenza / Delayed / 5.1-5.1
    gastroesophageal reflux / Delayed / 2.7-2.7

    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.
    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; 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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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 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; 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.
    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.
    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.
    Hydroxyprogesterone: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of hydroxyprogesterone; monitor for potential reduction in efficacy. Hydroxyprogesterone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    Tofacitinib: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of tofacitinib; monitor for potential reduction in efficacy. Tofacitinib 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.
    Trabectedin: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of trabectedin; monitor for potential reduction in efficacy. Trabectedin 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.
    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.
    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.
    Vardenafil: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of vardenafil; monitor for potential reduction in efficacy. Vardenafil is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    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) Use lesinurad and warfarin together with caution; warfarin may increase the systemic exposure of lesinurad. Warfarin is a mild inhibitor of CYP2C9 in vitro, and lesinurad is a CYP2C9 substrate.
    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.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no available human data on the use of lesinurad during pregnancy. 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).

    There is no information regarding the presence of lesinurad in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for lesinurad and any potential adverse effects on the breastfed infant from lesinurad or the underlying maternal condition.

    MECHANISM OF ACTION

    Lesinurad reduces serum uric acid concentrations by inhibiting the function of 2 transporter proteins involved in uric acid reabsorption in the kidney. Uric acid transporter 1 (URAT1), which is responsible for the majority of the reabsorption of filtered uric acid from the renal tubular lumen and 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.

    PHARMACOKINETICS

    Lesinurad is administered orally. 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.
     
    Affected cytochrome P450 (CYP450) isoenzymes, and other enzymes and drug transporters: CYP2C9, CYP3A4, epoxide hydrolase
    Lesinurad is a substrate for CYP2C9. 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

    The absolute bioavailability of lesinurad is 100%. It is 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. The Cmax and exposure (AUC) increase proportionally with single oral doses from 5 to 1200 mg. Administration with a high-fat meal decreases Cmax by up to 18% but does not alter the AUC when compared with the fasted state. Lesinurad was administered with food in clinical trials.