Rhabdomyolysis risk from febuxostat

Thursday, 30 Jul 2015

A combination of chronic kidney disease and statin therapy may represent a risk for the rare side-effect of rhabdomyolysis in patients treated with febuxostat for gout, a case report from St Vincent’s Hospital in Sydney suggests.

Dr Debasish Ghosh and colleagues, writing in the MJA, described a 68 year old man with stage 3 CKD and ischaemic heart disease who had taken simvastatin and gemfibrozil for 12 years.

He started febuxostat, the novel xanthine oxidase recently approved for use in Australia, for long-standing polyarticular tophaceous gout, having previously had anaphylactic reactions to acute allopurinol and then colchicine.

A month later the patient presented with rhabdomyolysis, confirmed by a serum creatinine kinase of 48,200 U/L and myoglobin in his urine. A marked deterioration in renal function culminated in a serum creatinine of 833 μmol/L and eGFR of 6 mL/min/1.73m2. Haemodialysis over 8 days gradually restored his renal function.

After 23 days in hospital he was discharged on benzbromarone, obtained through the Special Access Scheme, which successfully reduced the plasma urate concentration to 0.26 mmol/L.

“Rhabdomyolysis is noted as a rare side effect in the product information for febuxostat, following post-marketing experience, but there has been only a single published case report,” Dr Ghosh said.

“Febuxostat was considered to be the likely dominant precipitating factor and was withdrawn, as were simvastatin and gemfibrozil,” he said. “He had used these two medications for 12 years, but febuxostat had only recently been prescribed.”

CKD was likely to be a contributing factor. “Although the product information for febuxostat indicates that there is no need for dose adjustment in patients with moderate renal impairment, prescribers need to be cautious,” the doctors advised.

Options for reducing plasma urate levels to prevent recurrent acute and tophaceous gout are limited, especially in patients with impaired renal function.

Reducing this patient’s plasma urate levels was a critical goal, given his deteriorating renal function, progressive joint damage, and recurrent and severely painful acute gout.

Febuxostat was now clearly contraindicated and probenecid has limited efficacy when the GFR is <30 mL/minute.

Benzbromarone is more effective than probenecid in patients with impaired renal function and is a reasonable option, but careful monitoring of liver function is essential because of rare reports of serious hepatic toxicity, they said.

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