(le SIN ure ad)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Zurampic: 200 mg
Brand Names: U.S.
- Antigout Agent
- Uric Acid Transporter 1 (URAT1) Inhibitor
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.
Extensive. Vdss: ~20 L
Metabolized oxidatively primarily via CYP2C9l plasma exposure to metabolites is minimal; metabolites are not known to contribute to activity
Urine (63%; ~30% as unchanged drug); feces (32%)
Time to Peak
Within 1 to 4 hours
>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.
Severe renal impairment (CrCl <30 mL/minute), end-stage renal disease (ESRD), dialysis, kidney transplant recipients, tumor lysis syndrome, or Lesch-Nyhan syndrome
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.
Refer to adult dosing.
Dosing: Renal Impairment
Preexisting renal impairment:
Estimated CrCl ≥60 mL/minute: No dosage adjustment necessary.
Estimated CrCl 45 to <60 mL/minute: No dosage adjustment is necessary; monitor more frequently.
Estimated CrCl 30 to <45 mL/minute: Treatment may be less effective (based on limited experience) and should not be initiated.
Estimated CrCl <30 mL/minute: Use is contraindicated.
End-stage renal disease (ESRD) or patients on dialysis: Use is contraindicated.
Renal toxicity during treatment: Estimated CrCl persistently <45 mL/minute: Discontinue treatment.
Dosing: Hepatic Impairment
Mild to moderate impairment (Child-Pugh class A and B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C): Use is not recommended (has not been studied).
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).
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.
ARIPiprazole: CYP3A4 Inducers may decrease the serum concentration of ARIPiprazole. Management: Double the oral aripiprazole dose and closely monitor response. Reduce oral aripiprazole dose to 10-15 mg/day (for adults) if the inducer is discontinued. Avoid use of CYP3A4 inducers for more than 14 days with extended-release injectable aripiprazole. Consider therapy modification
Aspirin: May diminish the therapeutic effect of Lesinurad. Monitor therapy
Ceritinib: May increase the serum concentration of CYP2C9 Substrates. Management: Concurrent use of ceritinib with a CYP2C9 substrate that has a narrow therapeutic index (e.g., warfarin, phenytoin) should be avoided when possible. Monitor therapy
CloZAPine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CloZAPine. Monitor therapy
Contraceptives (Estrogens): Lesinurad may decrease the serum concentration of Contraceptives (Estrogens). Management: Use of an additional, nonhormonal contraceptive is recommended in patients being treated with lesinurad who desire effective contraception. Consider therapy modification
Contraceptives (Progestins): Lesinurad may decrease the serum concentration of Contraceptives (Progestins). Management: Use of an additional, nonhormonal contraceptive is recommended in patients being treated with lesinurad who desire effective contraception. Consider therapy modification
CYP2C9 Inducers (Strong): May increase the metabolism of CYP2C9 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates. Monitor therapy
CYP2C9 Inhibitors (Strong): May decrease the metabolism of CYP2C9 Substrates. Consider therapy modification
Dabrafenib: May decrease the serum concentration of CYP2C9 Substrates. Management: Seek alternatives to the CYP2C9 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Enzalutamide: May decrease the serum concentration of CYP2C9 Substrates. Management: Concurrent use of enzalutamide with CYP2C9 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C9 substrate should be performed with caution and close monitoring. Consider therapy modification
HYDROcodone: CYP3A4 Inducers (Weak) may decrease the serum concentration of HYDROcodone. Monitor therapy
Lumacaftor: May decrease the serum concentration of CYP2C9 Substrates. Lumacaftor may increase the serum concentration of CYP2C9 Substrates. Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP2C9 Substrates. Management: Use CYP2C9 substrates at the lowest recommended dose, and monitor closely for adverse effects, during and in the 2 weeks following mifepristone treatment. Consider therapy modification
NiMODipine: CYP3A4 Inducers (Weak) may decrease the serum concentration of NiMODipine. Monitor therapy
SAXagliptin: CYP3A4 Inducers may decrease the serum concentration of SAXagliptin. Monitor therapy
Valproate Products: May increase the serum concentration of Lesinurad. Avoid combination
Frequency not always defined. Incidence reported in combination with a xanthine oxidase inhibitor.
Cardiovascular: Cerebrovascular accident, myocardial infarction
Central nervous system: Headache (5%)
Gastrointestinal: Gastroesophageal reflux disease (3%)
Infection: Influenza (5%)
Renal: Increased serum creatinine (3% to 7%; 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 (≤4%), nephrolithiasis (3%), acute renal failure
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).
• 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.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• CYP2C9 poor metabolizers: Lesinurad exposure is ~1.8 fold higher in CYP2C9 poor metabolizers; use with caution.
• 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).
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 every 2 to 5 weeks during uric acid lowering therapy titration then every 6 months (Khanna 2012).
Adverse events were not observed in animal reproduction studies.
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.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience headache, flu-like signs, or heartburn. Have patient report immediately to prescriber signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, or weight gain), nausea, vomiting, side pain, or lower back pain (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.