Can Eplerenone Cause Gout?
Eplerenone is not documented to cause gout in major clinical guidelines or trials. The primary adverse effects of eplerenone are hyperkalemia and worsening renal function, not hyperuricemia or gout 1.
Known Adverse Effects of Eplerenone
The established side effects of eplerenone based on large randomized controlled trials and clinical guidelines include:
- Hyperkalemia - the most common and potentially dangerous adverse effect, occurring when potassium rises above 5.5 mmol/L 1
- Worsening renal function - manifested as rising creatinine levels, particularly in elderly patients and those with baseline renal impairment 1, 2
- Symptomatic hypotension - though this often improves with time 1
- Common side effects (occurring in up to 10% of patients) include nausea, diarrhea, dizziness, and headache 1
Why Gout Is Not Associated with Eplerenone
The European Society of Cardiology guidelines from 2008 and 2012, which provide comprehensive safety profiles for eplerenone based on the landmark EPHESUS trial (6,632 patients), do not list gout or hyperuricemia as adverse effects 1. Similarly, the American Heart Association/American College of Cardiology guidelines addressing eplerenone use do not mention gout as a concern 1.
In contrast, the guidelines specifically note that measurement of serum uric acid and treatment with allopurinol is recommended for patients with cyanotic congenital heart disease who have a history of gout, but this is related to the underlying condition, not to eplerenone therapy 1.
Distinction from Other Diuretics
Unlike loop diuretics (such as furosemide), which can cause hyperuricemia and precipitate gout attacks, eplerenone is a potassium-sparing aldosterone antagonist that does not share this mechanism 1. The primary electrolyte concern with eplerenone is hyperkalemia, not hyperuricemia 3, 2.
Clinical Monitoring Recommendations
When prescribing eplerenone, the focus should be on monitoring for its actual adverse effects 1:
- Check serum potassium and renal function at baseline, then at 1 and 4 weeks after initiation
- Continue monitoring at 1,2,3, and 6 months after achieving maintenance dose, then every 6 months thereafter
- Reduce dose by half if potassium rises to >5.5 mmol/L or creatinine rises to >220 μmol/L (2.5 mg/dL)
- Stop immediately if potassium rises to >6.0 mmol/L or creatinine rises to >310 μmol/L (3.5 mg/dL)
Common Pitfall to Avoid
Do not confuse eplerenone's adverse effect profile with that of loop diuretics or thiazides, which can cause hyperuricemia and gout. Eplerenone's mechanism as a selective mineralocorticoid receptor antagonist does not involve uric acid metabolism 3.