Allopurinol/lesinurad Disease Interactions

No studies with febuxostat or lesinurad have been conducted in patients with secondary hyperuricemia (including organ transplant recipients). The use of these drugs is contraindicated in patients where the uric acid formation is greatly increased, such as patients with malignant disease, tumor lysis syndrome or Lesch-Nyhan syndrome.

The use of lesinurad is contraindicated in patients with severe renal impairment, end stage renal disease, kidney transplant recipient and patients on dialysis.

Bone marrow suppression has been reported in patients receiving allopurinol; however, most of these patients were receiving concomitant medications with the known potential to cause such an effect. The suppression has occurred from as early as 6 weeks to as long as 6 years after the initiation of allopurinol therapy. Therapy with allopurinol should be administered cautiously to patients with or predisposed to bone marrow suppression.

Patients with pre-existing kidney conditions, including chronic kidney disease or a history of kidney stones, may be at increased risk for worsening of kidney function or acute kidney injury due to xanthine calculi during treatment with this drug. Ensure adequate hydration to maintain a daily urine output of at least 2 liters in adults and 2 liters/m2/day (or 100 mL/m2/hour) in pediatric patients. Maintaining a neutral to slightly alkaline urine pH is also recommended to prevent xanthine calculi and reduce urate precipitation. Renal function should be closely monitored, especially during the early stages of therapy.

Allopurinol may cause hepatotoxicity. In patients with pre-existing liver disease, monitor liver enzymes periodically during the early stages of therapy. Discontinue treatment in patients with elevated liver enzymes.

Allopurinol and its primary active metabolite, oxipurinol, are eliminated by the kidneys, and any changes in renal function will likely increase exposure. Additionally, treatment with allopurinol may result in renal impairment due to formation of xanthine calculi or due to precipitation of urates in patients receiving concomitant uricosuric agents. Patients with pre-existing renal disease, may be at increased risk for worsening renal impairment due to xanthine calculi or precipitation of urates while receiving treatment. These patients require lower dosages of allopurinol than normal to control serum urate levels and close monitoring of laboratory parameters of renal function to reassess the patient's dosage. Treatment with allopurinol tablets has not been studied in pediatric patients with severe renal impairment (eGFR less than 20 mL/min) or on dialysis.

Major adverse cardiovascular events (cardiovascular deaths, non- fatal myocardial infarctions and non- fatal strokes), were reported during clinical trials with some antihyperuricemic agents, such as febuxostat and lesinurad. Although a causal relationship has not been established, caution is advised when used in patients with cardiovascular disease. Monitoring for signs or symptoms of myocardial infarction or stroke is recommended.

No studies have been conducted in patients with severe hepatic impairment (Child-Pugh Class C), therefore caution should be exercised if using febuxostat or lesinurad on these patients. No dose adjustment is necessary in patients with mild or moderate hepatic impairment.