1) COMMON: The most common adverse events reported in patients treated with lesinurad in combination with a xanthine oxidase inhibitor include headache, increased serum creatinine, influenza and gastroesophageal reflux.
2) SERIOUS: During clinical trials, renal adverse events including renal impairment and renal failure have occurred with therapy and were more frequently associated with monotherapy (not recommended) and increased dosage. Potentially severe cardiovascular events, including cardiovascular death, non-fatal myocardial infarction and stroke, were reported infrequently.

1) OVERDOSE: Limited data. Clinical events are anticipated to be an extension of adverse events reported with lesinurad therapy.

1) Treatment is symptomatic and supportive. Monitor serum creatinine and renal function closely following exposure.

1) Treatment is symptomatic and supportive. Monitor renal function closely. Monitor vital signs. Obtain a baseline ECG and institute continuous cardiac monitoring in patients that develop evidence of cardiac toxicity.

1) PREHOSPITAL: Gastrointestinal decontamination is unlikely to be necessary following a minor exposure. Consider activated charcoal if the overdose is significant, the exposure is recent, the patient is not vomiting, and is able to maintain their airway.
2) HOSPITAL: Consider activated charcoal following a significant exposure, the overdose is recent, the patient is not vomiting, and is able to maintain their airway.

1) Airway management is unlikely to be necessary following a minor or moderate exposure unless other toxic agents have been administered concurrently.

1) There is no known antidote for lesinurad.

1) Lesinurad is extensively bound to plasma proteins (greater than 98%); therefore, hemodialysis is UNLIKELY to be effective.

1) HOME CRITERIA: Asymptomatic adults with an inadvertent ingestion of 1 to 2 extra doses or an adult with mild gastrointestinal symptoms can be monitored at home. An asymptomatic child with an inadvertent ingestion (1 tablet) or mild gastrointestinal symptoms can be monitored at home with adult supervision.
2) OBSERVATION CRITERIA: Patients that have more than mild clinical symptoms or had a deliberate ingestion should be referred to a healthcare facility for evaluation including assessment of renal function (ie, serum creatinine, nephrolithiasis) and treatment.
3) ADMISSION CRITERIA: Patients that develop persistent signs or symptoms of acute renal impairment or failure or evidence of cardiac toxicity should be admitted.
4) CONSULT CRITERIA: Consult a nephrologist as needed in patients that develop signs and symptoms of acute kidney injury. Consult a medical toxicologist or poison center for patients with severe toxicity or in whom the diagnosis is unclear.

1) Tmax was 1 to 4 hours following a single oral dose. Lesinurad is greater than 98% protein bound, primarily to albumin. Mean steady-state volume of distribution was 20 L with IV administration. Urinary recovery of radiolabeled lesinurad was 63% and fecal recovery was 32% within 7 days. Greater than 60% of the dose was recovered within the first 24 hours. The elimination half-life is about 5 hours. Accumulation is not observed following multiple doses.

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) No teratogenic effects were observed when animals were administered lesinurad doses up to approximately 45 times the maximum recommended human dose (MRHD) (Prod Info ZURAMPIC(R) oral tablets, 2015).

1) There are no studies of lesinurad use during human pregnancy. Exercise caution when administering to a pregnant woman (Prod Info ZURAMPIC(R) oral tablets, 2015).

1) No effect on survival was observed when animals were administered lesinurad doses up to approximately 45 times the MHRD. In addition, no effect on delivery, growth, or development was observed when animals were administered lesinurad doses approximately 5 times the MRHD (Prod Info ZURAMPIC(R) oral tablets, 2015).

1) It is not known whether lesinurad is excreted in human breast milk, if there are effects on the infant, or if there are effects on breast milk production. Exercise caution when administering to a nursing woman and weigh the benefits of breastfeeding with the risk to the infant (Prod Info ZURAMPIC(R) oral tablets, 2015).

1) Lesinurad has been detected in the milk of lactating animals (Prod Info ZURAMPIC(R) oral tablets, 2015).

1) There were no reports of adverse effects on fertility or reproductive performance in animals administered lesinurad at approximately 15 times the MHRD dose on a mg/m(2) basis (Prod Info ZURAMPIC(R) oral tablets, 2015).

1) At the time of this review, the manufacturer does not report any carcinogenic potential of lesinurad in humans (Prod Info ZURAMPIC(R) oral tablets, 2015).

1) In oral carcinogenicity studies, Sprague-Dawley rats administered lesinurad for 91 to 100 weeks at oral doses up to approximately 35 times the maximum recommended human dose (MRHD) on an AUC basis in males and females and TgRasH2 mice administered lesinurad for 26 weeks at oral doses up to 125 and 250 mg/kg day in both males and females did not produce any tumors (Prod Info VIBERZI oral tablets, 2015).

A) Patients that develop persistent signs or symptoms of acute renal impairment or failure or evidence of cardiac toxicity should be admitted.

A) Asymptomatic adults with an inadvertent ingestion of 1 to 2 extra doses or an adult with mild gastrointestinal symptoms can be monitored at home. An asymptomatic child with an inadvertent ingestion (1 tablet) or mild gastrointestinal symptoms can be monitored at home with adult supervision.

A) Consult a nephrologist as needed in patients that develop signs and symptoms of acute kidney injury. Consult a medical toxicologist or poison center for patients with severe toxicity or in whom the diagnosis is unclear.

A) Patients that have more than mild clinical symptoms or had a deliberate ingestion should be referred to a healthcare facility for evaluation including assessment of renal function (ie, serum creatinine, nephrolithiasis) and treatment.

1) Gastrointestinal decontamination is unlikely to be necessary following a minor exposure.

1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
2) CHARCOAL DOSE

1) MANAGEMENT OF MILD TO MODERATE TOXICITY
2) MANAGEMENT OF SEVERE TOXICITY

1) Monitor renal function closely.
2) Monitor vital signs as indicated.
3) Obtain a baseline ECG and consider continuous cardiac monitoring in patients that develop any evidence of cardiovascular symptoms.

1) Cmax of lesinurad was 6 mcg/mL (coefficient of variation, 31%) with oral administration of a single 200-mg dose in healthy volunteers. Cmax increased dose proportionally with single oral doses of 5 to 1200 mg (greater than the approved dose) (Prod Info ZURAMPIC(R) oral tablets, 2015).