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Lesinurad

Medically reviewed by Drugs.com. Last updated on May 21, 2020.

Pronunciation

(le SIN ure ad)

Index Terms

  • Zurampic

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Zurampic: 200 mg [DSC]

Brand Names: U.S.

  • Zurampic [DSC]

Pharmacologic Category

  • Antigout Agent
  • Uric Acid Transporter 1 (URAT1) Inhibitor

Pharmacology

Lesinurad inhibits the function of transporter proteins involved in renal uric acid reabsorption (uric acid transporter 1 [URAT1] and organic anion transporter 4 [OAT4]), and lowers serum uric acid levels and increases renal clearance and fractional excretion of uric acid in patients with gout.

Absorption

Rapid

Distribution

Extensive. Vdss: ~20 L

Metabolism

Metabolized oxidatively primarily via CYP2C9l plasma exposure to metabolites is minimal; metabolites are not known to contribute to activity

Excretion

Urine (63%; ~30% as unchanged drug); feces (32%)

Time to Peak

Within 1 to 4 hours

Half-Life Elimination

~5 hours

Protein Binding

>98%; primarily to albumin

Special Populations: Renal Function Impairment

Lesinurad exposure is increased by 30% in patients with estimated CrCl 60 to <90 mL/minute, 50% to 73% in patients with estimated CrCl 30 to <60 mL/minute, and 113% in patients with estimated CrCl <30 mL/minute; when compared with patients with normal renal function.

Special Populations: Hepatic Function Impairment

In patients with mild (Child-Pugh class A) and moderate (Child-Pugh class B), following administration of a single 400 mg dose, the AUC was 7% and 33% higher, respectively, when compared with patients with normal hepatic function.

Use: Labeled Indications

Hyperuricemia associated with gout: Treatment of hyperuricemia associated with gout (in combination with a xanthine oxidase inhibitor) in patients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor alone.

Limitations of use: Lesinurad is not recommended for the treatment of asymptomatic hyperuricemia. Lesinurad should not be used as monotherapy.

Contraindications

Severe renal impairment (CrCl <30 mL/minute), end-stage renal disease (ESRD), dialysis, kidney transplant recipients, tumor lysis syndrome, or Lesch-Nyhan syndrome

Dosing: Adult

Hyperuricemia associated with gout: Oral: 200 mg once daily (in combination with a xanthine oxidase inhibitor, including allopurinol or febuxostat); maximum dose: 200 mg once daily. Note: If treatment with the xanthine oxidase inhibitor therapy is interrupted, lesinurad should also be withheld.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Administration

Oral: Administer in the morning with food and water. Administer at the same time in the morning as the dose of xanthine oxidase inhibitor. Advise patients to stay well hydrated (eg 2 L of fluids/day).

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F). Protect from light.

Drug Interactions

Alpelisib: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Monitor therapy

Aspirin: May diminish the therapeutic effect of Lesinurad. Monitor therapy

CloZAPine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CloZAPine. Monitor therapy

CYP2C9 Inducers (Moderate): May decrease the serum concentration of Lesinurad. Monitor therapy

CYP2C9 Inhibitors (Moderate): May increase the serum concentration of Lesinurad. Monitor therapy

Estrogen Derivatives (Contraceptive): Lesinurad may decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Use of an additional, nonhormonal contraceptive is recommended in patients being treated with lesinurad who desire effective contraception. Consider therapy modification

Lumacaftor and Ivacaftor: May decrease the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may increase the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Monitor therapy

NiMODipine: CYP3A4 Inducers (Weak) may decrease the serum concentration of NiMODipine. Monitor therapy

Progestins (Contraceptive): Lesinurad may decrease the serum concentration of Progestins (Contraceptive). Management: Use of an additional, nonhormonal contraceptive is recommended in patients being treated with lesinurad who desire effective contraception. Consider therapy modification

Rifapentine: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Monitor therapy

Selpercatinib: CYP3A4 Inducers (Weak) may decrease the serum concentration of Selpercatinib. Monitor therapy

Tacrolimus (Systemic): CYP3A4 Inducers (Weak) may decrease the serum concentration of Tacrolimus (Systemic). Monitor therapy

Ubrogepant: CYP3A4 Inducers (Weak) may decrease the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a weak CYP3A4 inducer. Consider therapy modification

Valproate Products: May increase the serum concentration of Lesinurad. Avoid combination

Adverse Reactions

Incidence reported in combination with a xanthine oxidase inhibitor.

1% to 10%:

Central nervous system: Headache (5%)

Gastrointestinal: Gastroesophageal reflux disease (3%)

Infection: Influenza (5%)

Renal: Increased serum creatinine (≤6%; 1.5 x to <2.0 x baseline: 4%; ≥2.0 x baseline: 2%; most elevations were transient and resolved without therapy interruption), renal failure (2%)

Frequency not defined:

Cardiovascular: Cerebrovascular accident, myocardial infarction

Renal: Acute renal failure

<1%, postmarketing, and/or case reports: Nephrolithiasis

ALERT: U.S. Boxed Warning

Nephrotoxicity:

Acute renal failure has occurred with lesinurad and was more common when lesinurad was given alone.

Appropriate use:

Lesinurad should be used in combination with a xanthine oxidase inhibitor.

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular events: Major cardiac adverse events (cardiovascular deaths, non-fatal MI, or non-fatal strokes) were observed in clinical trials, although a causal relationship with lesinurad was not established.

• Gout flare: Following initiation of uric acid lowering therapy, gout may flare due to mobilization of urate from tissue deposits; gout flare prophylaxis is recommended when initiating lesinurad treatment. Lesinurad treatment may continue during gout flare and management of the flare.

• Nephrotoxicity: Lesinurad, when used concurrently with a xanthine oxidase inhibitor, is associated with an increased incidence of serum creatinine elevations (generally reversible). [US Boxed Warning]: Acute renal failure has occurred with lesinurad and was more common when lesinurad was given alone. Renal failure (acute and chronic) and nephrolithiasis have also been reported (when used in combination with a xanthine oxidase inhibitor). The incidence of renal-related adverse events was also higher with lesinurad dosed at 400 mg (which is higher than the approved dose).

Disease-related concerns:

• Renal impairment: Evaluate renal function prior to treatment initiation and periodically, as clinically indicated, thereafter (more frequently in patients with estimated CrCl <60 mL/minute or with serum creatinine elevations 1.5 to 2 times the baseline level). Lesinurad should not be initiated in patients with estimated CrCl <45 mL/minute and is contraindicated with estimated CrCl <30 mL/minute. Lesinurad is not expected to be effective in patients with estimated CrCl <30 mL/minute, end-stage renal disease (ESRD), and/or on dialysis. Interrupt treatment if serum creatinine is elevated to >2 times baseline level. Interrupt treatment and measure serum creatinine if symptoms indicative of acute uric acid nephropathy (including flank pain, nausea, or vomiting) occur; do not restart without determining the cause of the serum creatinine abnormality.

• Secondary hyperuricemia: Lesinurad has not been studied in patients with secondary hyperuricemia (including organ transplant recipients); use is contraindicated in patients with tumor lysis syndrome or Lesch-Nyhan syndrome, where the uric acid formation rate is greatly increased.

Special populations:

• CYP2C9 poor metabolizers: Lesinurad exposure is ~1.8 fold higher in CYP2C9 poor metabolizers; use with caution.

Other warnings/precautions:

• Appropriate use: [US Boxed Warning]: Lesinurad should only be used in combination with a xanthine oxidase inhibitor; do not use as monotherapy. Lesinurad should be added when target serum uric acid levels are not achieved with a medically appropriate dose of single-agent xanthine oxidase inhibitor therapy. Lesinurad use is not recommended in patients taking allopurinol daily doses <300 mg (or <200 mg in patients with estimated CrCl <60 mL/minute).

Monitoring Parameters

Serum creatinine and estimated CrCl prior to treatment initiation and periodically, as clinically indicated, thereafter (more frequently in patients with estimated CrCl <60 mL/minute or with serum creatinine elevations 1.5 to 2 times the baseline level). Serum uric acid levels after every dose titration until desired level is achieved, then every 6 months (symptomatic patients) or every 12 months (all patients on urate-lowering therapy, regardless of symptoms) (FitzGerald 2018).

Reproductive Considerations

All forms of hormonal contraceptives (eg, oral, injectable, topical) may be less effective during therapy with lesinurad. Additional methods of contraception are recommended during therapy.

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies.

Patient Education

What is this drug used for?

• It is used to lower uric acid in the blood.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

• Flu-like signs

• Heartburn

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain

• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight

• Chest pain

• Nausea

• Vomiting

• Side pain

• Lower back pain

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.