Generic Name and Formulations:
Lesinurad, allopurinol 200mg/200mg, 200mg/300mg; tabs.
Indications for DUZALLO:
Hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with a medically appropriate daily dose of allopurinol alone.
Limitations Of use:
Not for treatment of asymptomatic hyperuricemia.
Take in the AM with food and water. ≥18yrs: 1 tab daily. Patients on daily allopurinol dose 200mg: initially one 200mg/200mg tab daily; 300mg: initially one 200mg/300mg tab daily; >300mg: initially one tab in place of an equal portion of the total daily allopurinol dose; if <300mg (or <200mg with eCLCr <60mL/min): not recommended.
<18yrs: not established.
Severe renal impairment (eCLCr <30mL/min), ESRD, kidney transplant recipients, or dialysis patients. Tumor lysis syndrome or Lesch-Nyhan syndrome.
Risk of acute renal failure. Assess renal function prior to initiation and periodically thereafter. Renal impairment (eCLCr <45mL/min): do not initiate. If eCLCr <60mL/min or with serum creatinine (SCr) elevations 1.5–2X pre-treatment value: monitor more frequently; if SCr >2X pre-treatment value: interrupt treatment. Discontinue therapy if eCLCr is persistently <45mL/min. Maintain adequate hydration (2 liters of liquid per day). Give gout flare prophylaxis if patient not currently taking lesinurad. Discontinue immediately if rash occurs. Evaluate liver function if anorexia, weight loss, or pruritus develops. Pre-existing liver disease: perform LFTs periodically. Severe hepatic impairment: not recommended. Females should use additional non-hormonal methods of contraception. Pregnancy. Nursing mothers.
Caution with concomitant moderate CYP2C9 inhibitors (eg, fluconazole, amiodarone) and in CYP2C9 poor metabolizers. Antagonized by moderate CYP2C9 inducers (eg, rifampin, carbamazepine), aspirin >325mg/day. Antagonizes CYP3A substrates (eg, sildenafil, amlodipine). May affect sensitive CYP3A substrates (eg, HMG-CoA reductase inhibitors); monitor. Concomitant epoxide hydrolase inhibitors (eg, valproic acid): not recommended. May reduce efficacy of hormonal contraceptives. Potentiates azathioprine and mercaptopurine toxicity; reduce dose of these by ⅓ to ¼ of usual dose and monitor. Assess PT periodically with concomitant coumarin anticoagulants (eg, dicumarol, warfarin). May potentiate chlorpropamide, cyclosporine. Increased rash with ampicillin, amoxicillin. Monitor renal function with thiazides.
URAT1 inhibitor + xanthine oxidase inhibitor.
Headache, influenza, blood creatinine increased, GERD, skin rash; renal events, hepatotoxicity, cardiovascular events, drowsiness; rarely: bone marrow depression, severe hypersensitivity reactions (eg, eosinophilia, SJS, TEN).
Tabs—5, 30, 90