ZURAMPIC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZURAMPIC (ZURAMPIC).
Selective inhibitor of URAT1 (uric acid transporter 1) and OAT4 (organic anion transporter 4), increasing uric acid excretion and reducing serum uric acid levels.
| Metabolism | Primarily metabolized by CYP2C9 and to a lesser extent by CYP3A4 and CYP2C8; also undergoes glucuronidation via UGT1A1, UGT1A3, UGT1A9, and UGT2B7. |
| Excretion | Primarily renal (approximately 70% unchanged in urine), with minor biliary/fecal excretion (less than 10%). |
| Half-life | Terminal elimination half-life is approximately 5 hours; clinically, this supports twice-daily dosing. |
| Protein binding | Approximately 90% bound to plasma proteins (mainly albumin). |
| Volume of Distribution | Approximately 0.6 L/kg, suggesting distribution largely into extracellular fluid. |
| Bioavailability | Oral bioavailability is approximately 100% (well absorbed). |
| Onset of Action | Oral: reduction in serum uric acid observed within 2 hours; peak effect at 3-4 hours. |
| Duration of Action | Duration of urate-lowering effect is approximately 12-24 hours based on serum uric acid suppression; clinical effect wanes with drug clearance, requiring twice-daily administration. |
| Molecular Weight | 256.26 |
200 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in patients with eGFR < 30 mL/min/1.73 m². No dose adjustment required for eGFR ≥ 30 mL/min/1.73 m². |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C); use with caution. |
| Pediatric use | Safety and efficacy in pediatric patients (<18 years) have not been established. |
| Geriatric use | No specific dose adjustment recommended. Monitor renal function due to age-related decline. |
| 1st trimester | No adequate human data; animal studies show embryotoxicity at high doses. Avoid in first trimester unless benefit outweighs risk. |
| 2nd trimester | Limited human data; potential for fetal harm. Use only if clearly needed. |
| 3rd trimester | Limited human data; risk of neonatal hyperuricemia. Avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for ZURAMPIC (ZURAMPIC).
| Placental transfer | Expected to cross placenta based on molecular weight (about 256 Da) and animal studies showing fetal exposure. |
| Breastfeeding | Not known if excreted in human milk. Due to potential for serious adverse reactions, discontinue nursing or discontinue drug, considering importance to mother. |
| Lactation Rating |
■ FDA Black Box Warning
Not approved for the treatment of asymptomatic hyperuricemia; may increase the risk of acute gout flares and cardiovascular events.
| Serious Effects |
Severe renal impairment (eGFR < 30 mL/min)End-stage renal diseaseDialysis patientsAcute uric acid nephropathyConcomitant use with xanthine oxidase inhibitors (allopurinol, febuxostat) to avoid renal toxicity
| Precautions | Risk of acute gout flares upon initiation, Increased risk of cardiovascular events (non-significant trend), Renal impairment (eGFR <30 mL/min not studied), Hepatic impairment (not recommended in severe impairment), Drug interactions with CYP2C9 inhibitors/inducers and NSAIDs |
| Food/Dietary | No specific food interactions reported. Maintain adequate hydration to prevent urate nephropathy or kidney stones. Avoid alcohol and purine-rich foods (e.g., red meat, shellfish) as they may increase uric acid levels and counteract drug efficacy. |
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| L4 (Possibly Hazardous) |
| Teratogenic Risk | Zurampic (lesinurad) is contraindicated in pregnancy. Animal studies show fetal harm at exposures similar to human doses. No human data; risk cannot be excluded. First trimester: potential for major malformations. Second/third trimesters: risk of fetal toxicity (e.g., renal impairment). Avoid use. |
| Fetal Monitoring | Monitor serum creatinine and uric acid levels. Assess renal function and urine output. Watch for signs of acute renal failure, especially in setting of volume depletion. Fetal monitoring: consider ultrasound for renal anomalies if inadvertent exposure. |
| Fertility Effects | Animal studies: no impairment of fertility at clinically relevant doses. Human data lacking. Potential indirect effects via hyperuricemia or renal impairment, but no specific evidence. |
| Clinical Pearls | Zurampic (lesinurad) is a uric acid reabsorption inhibitor used in combination with a xanthine oxidase inhibitor (e.g., allopurinol or febuxostat) for chronic gout. Do not use as monotherapy. Monitor renal function before and during therapy; contraindicated if CrCl <45 mL/min. Avoid use with aspirin >325 mg/day (reduces efficacy). Assess for acute gout flares upon initiation; prophylaxis with NSAIDs or colchicine is recommended for the first 6 months. |
| Patient Advice | Take Zurampic exactly as prescribed, always with a xanthine oxidase inhibitor like allopurinol or febuxostat. · Stay well hydrated to reduce risk of kidney stones. · Report any signs of allergic reaction, rash, or difficulty breathing immediately. · You may experience gout flares initially; continue medication as directed and use prescribed flare medications. · Avoid high-dose aspirin (more than 325 mg/day) as it may reduce effectiveness. · Do not take Zurampic if you have severe kidney problems; tell your doctor about all kidney issues. · Keep all follow-up appointments for blood tests to monitor kidney function and uric acid levels. |