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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZURAMPIC (ZURAMPIC).
| Breastfeeding | No data on presence in human milk, effects on infant, or milk production. M/P ratio unknown. Due to potential for serious adverse reactions, breast-feeding is not recommended during therapy and for 2 weeks after last dose. |
| 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. |
■ 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 |
["Concomitant use with a xanthine oxidase inhibitor (e.g., allopurinol, febuxostat)","Severe renal impairment (eGFR <30 mL/min)","Acute gout flare (until symptoms resolve)","Hypersensitivity to the drug or any component"]
| 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"] |
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| 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. |