II. Indications
-
Gouty Arthritis (chronic, refractory)
- Must be used in combination with Xanthine Oxidase Inhibitor (Allopurinol or Febuxostat)
III. Contraindications
- Renal Impairment (GFR <30-45 mL/min) including end-stage renal disease and those on Hemodialysis
- Renal Transplant
- Tumor Lysis Syndrome
- Lesch-Nyhan syndrome
- Severe hepatic Impairment
IV. Mechanism
- Selective Uricosuric (increases renal Uric Acid excretion)
- Blocks Uric Acid renal reabsorption via blockade of 2 apical transporters
- Uric Acid Transporter 1 Inhibitor (URAT1 Inhibitor)
- Organic Anion Transporter 4 Inhibitor (OAT-4 Inhibitor)
V. Medications
- Lesinurad (Zurampic): 200 mg tabs
-
Allopurinol with Lesinurad (Duzallo)
- As of 2017, costs $12/day (compared with $3/day for Allopurinol and probenacid)
- (2017) Presc Lett 24(11): 64
VI. Dosing
- Adults: 200 mg orally each morning
VII. Adverse Effects
-
Acute Renal Failure (black box warning)
- Monitor Renal Function at baseline and periodically during treatment
- Do NOT use as Uric Acid monotherapy
- Must be taken with Xanthine Oxidase Inhibitor (Allopurinol or Febuxostat)
- Allopurinol dose must be at least 300 mg/day (at least 200 if CrCl <60 ml/min)
- Cardiovascular events
VIII. Safety
- Unknown safety in Lactation
- Unknown safety in pregnancy
IX. Drug Interactions
-
Oral Contraceptives
- Lesinurad may reduce Oral Contraceptive efficacy
- Use non-Hormonal Contraception
-
CYP2C9 Inhibitors (e.g. Fluconazole, Amiodarone) and CYP2C9 poor metabolizers
- May increase Lesinurad levels
X. Resources
- Lesinurad (FDA package insert)