Products
Lesinurad was approved in the US in 2015, in the EU in 2016, and in many countries in 2017 in film-coated tablet form (Zurampic). A fixed-dose combination with allopurinol was released in the US in 2017 (Duzallo), in the EU in 2018, and in many countries in 2019.
Structure and properties
Lesinurad (C17H14BrN3O2S, Mr = 404.3 g/mol) is a brominated triazole, acetic acid and cyclopropyl naphthalene derivative.
Effects
Lesinurad (ATC M04AB05) has uricosuric properties. The effects are due to inhibition of the transporter URAT1 (urate transporter 1), which is responsible at the kidney for reabsorption of uric acid. As a result, more uric acid is excreted in the urine and the concentration in the blood decreases. Lesinurad additionally inhibits OAT4, which is involved in diuretic-induced hyperuricemia. It is completely absorbed and has a half-life of approximately 5 hours.
Indications
In combination with allopurinol for the treatment of hyperuricemia in adult patients with gout when target serum uric acid levels are not achieved with allopurinol alone.
Dosage
According to the SmPC. Film-coated tablets are taken once daily in the morning with breakfast and together with allopurinol. Patients should consume sufficient fluids during the day (e.g., two liters).
Contraindications
- Hypersensitivity
- Tumor lysis or Lesch-Nyhan syndrome
- Severe renal dysfunction, end-stage renal disease, renal transplant patients, or patients requiring dialysis
Monotherapy with lesinurad is not indicated. For complete precautions, see the drug label.
Interactions
Lesinurad is a substrate of CYP2C9, a weak CYP3A4 inducer, and an OAT and OATP inhibitor. Corresponding drug-drug interactions are possible. Other interactions have been described with epoxide hydrolase inhibitors (eg, valproate), salicylates (> 375 mg), and hormonal contraceptives.
Adverse effects
The most common potential adverse effects of combination therapy include headache, influenza, increased creatinine levels, and GERD (gastroesophageal reflux disease).
