Megaloblastic anemia has been rarely seen with tria¬mterene and with amiloride and it has been associated with the occurrence of aplastic anemia, albeit rarely. Spirono¬lactone does not have these serious adverse effects but causes bothersome gynecomastia.
3. Eplerenone
This selective aldosterone blocker has been shown to provide the same clinical benefits as spironolactone, but with a mild decrease in the incidence of two main adverse effects: gynecomastia and hyperkalemia. In the eplerenone post myocardial infarction and heart failure efficacy and survival study (EPHESUS), 6632 patients who were 3–14 days post acute myocardial infarction with an ejection fraction of less than 40% with heart failure and diabetes were randomized. Patients with a serum creatinine greater than 2.5 mg/dl (220 /xmol/L) or serum potassium greater than 5 mmol/L were excluded. At one-year follow up eplerenone-treated patients had an all-cause mortality of 14.45% versus 16.7% for spironolac¬tone-treated patients (one life saved for every 100 patients treated). But eplerenone-treated patients had slightly and significantly higher rates of worsening renal function (creatinine increased 0.06 mg/dl vs. 0.02 mg/dl) and of serious hyperkalemia (5. 5% vs. 3.9%). Because eplerenone was not shown to be significantly more effective than spironolactone, the drug may not replace the well-known spironolactone, except in men who show early signs of gynecomastia. Eplerenone has been shown to be as effective as losartan in reducing blood pressure in patients with high plasma renin activity and more effective than losartan in patients with low plasma renin activity.

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