Eplerenone (Inspra) for Hypertension


Am Fam Physician. 2004 Feb 15;69(4):915-916.

Synopsis: Eplerenone, a potassium-sparing diuretic similar to spironolactone, selectively blocks aldosterone to lower blood pressure. However, its safety profile is improved over spironolactone because of reduced progesterone and androgen-receptor effects. It is labeled for treatment of hypertension, either alone or in combination. It has been studied in postmyocardial infarction (MI) patients with left ventricular dysfunction.

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NameStarting dosageDose formApproximate monthly cost*

Eplerenone (Inspra)

1 50-mg tablet, orally daily

25-mg, 50-mg, and 100-mg tablets


*—Average wholesale cost, based on Red Book, Montvale, N.J.: Medical Economics Data, 2003.

NameStarting dosageDose formApproximate monthly cost*

Eplerenone (Inspra)

1 50-mg tablet, orally daily

25-mg, 50-mg, and 100-mg tablets


*—Average wholesale cost, based on Red Book, Montvale, N.J.: Medical Economics Data, 2003.

Safety: As with spironolactone, hyperkalemia can occur, with a prevalence ranging from 2.6 percent in patients with normal renal function to more than 10 percent in patients with mild renal dysfunction (creatinine clearance [CrCl] less than 70 mL per min).1 Hyperkalemia occurs more frequently in persons with diabetes, particularly when eplerenone is given with angiotensin-converting enzyme (ACE) inhibitors; 38 percent receiving this combination had hyperkalemia.1 Eplerenone is category B in pregnancy. It is contraindicated in patients with hyperkalemia (serum potassium more than 5.5 mEq per L), type 2 diabetes with microalbuminuria, or moderate renal dysfunction (CrCl less than 50 mL per min [0.83 mL per sec], serum creatinine more than 2.0 mg per dL (150 μmol per L) in men or more than 1.8 mg per dL (140 μmol per L) in women, and in those taking potassium supplements or with other potassium-sparing diuretics (amiloride, triamterene, or spironolactone).1 Eplerenone serum levels are increased when taken with detoconazole, erythromycin, saquinavir, verapamil, fluconazole, and grapefruit juice.1

Tolerability: Side effects are uncommon with eplerenone. Gynecomastia or mastodynia occur less often than with spironolactone (1.6 versus 6.9 percent). In clinical trials, rates of discontinuation were similar to those of placebo.1,6

Effectiveness: In patients with hypertension, eplerenone (50 to 200 mg daily) will lower blood pressure an average of 6 to 24 mm Hg systolic and 4 to 14 mm Hg diastolic.1,46 In comparative trials, eplerenone produced anti-hypertensive effects similar to those of enalapril, losartan, amlodipine, and spironolactone. It has lowered blood pressure particularly well in low-renin, salt-sensitive patients (mean diastolic reduction of 12.8 mm Hg, P <.001).5 There are no data from trials that examine the effect of eplerenone on mortality or morbidity in the treatment of hypertension.

There are no data on the effect of eplerenone in patients with heart failure except in post-MI patients who have an ejection fraction of less than 35 percent.3 In these patients, who also were receiving conventional therapy, the one-year mortality rate was lower in patients treated with eplerenone compared with placebo (11.8 versus 13.6 percent). Over 1.25 years, this difference translates into one fewer death for every 43 patients (range, 24 to 142) receiving eplerenone in conjunction with standard treatment. In addition, eplerenone reduced the combined outcome of deaths from cardiovascular causes or hospitalizations for cardiovascular events (26.7 versus 30 percent; number needed to treat: 30, 95 percent CI, 16 to 67). This effect was largely the result of a 21 percent relative reduction in sudden death among patients taking eplerenone.3

Price: A one-month supply of eplerenone will cost patients $113. This price is significantly higher than the cost of spironolactone, which is approximately $30 per month.

Simplicity: Inspra is supplied as 25-mg, 50-mg, or 100-mg tablets. The recommended starting dosage for antihypertensive treatment is one 50-mg tablet daily. Monitoring recommendations include determination of potassium concentrations every two weeks for the initial one to two months and then monthly thereafter, which would add considerably to the cost and complexity of therapy.1

Bottom line: Compared with other commonly used antihypertensive medications, eplerenone is effective in lowering blood pressure when used alone or as add-on therapy. However, mortality benefits related to antihypertensive treatment have not yet been shown, so it should not be considered a first-line treatment for hypertension. Mortality benefits have been observed with eplerenone in patients with left ventricular dysfunction who were receiving appropriate pharmacotherapy following an MI. It is unclear whether the advantages gained by an improved eplerenone side effect profile counter the cost or proven efficacy associated with appropriately dosed and monitored spironolactone therapy in patients with heart failure.

The Author

Charles T. Taylor, Pharm.D., B.C.P.S., is associate professor and vice chair in the Department of Pharmacy Practice, Auburn University Harrison School of Pharmacy, Auburn, Alabama.


show all references

1. Inspra [package insert]. Chicago, Ill: Pharmacia; 2003. Accessed January 23, 2004, at:

2. Weinberger M, Roniker B, Krause S, Weiss R. Eplerenone, a selective aldosterone blocker, in mild to moderate hypertension. Am J Hypertens. 2002;15:709–16.

3. Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348:1309–21.

4. White WB, Duprez D, St. Hillaire R, Krause S, Ronker B, Hamilton J, et al. Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension. Hypertension. 2003;41:1021–6.

5. Flack J, Oparil S, Pratt J, Ronker B, Garthwaite S, Kleiman J, et al. Efficacy and tolerability of eplerenone and losartan in hypertensive black and white patients. J Am Coll Cardiol. 2003;41:1148–55.

6. Coleman C, Reddy P, Song J, White C. Eplerenone: the first selective aldosterone receptor antagonist for the treatment of hypertension. Formulary 2002; 37:514–24. Accessed January 23, 2004, at:

STEPS drug updates cover Safety, Tolerability, Effectiveness, Price, and Simplicity.

The series coordinator of STEPS is Allen F. Shaughnessy, Pharm.D., director of medical education at Pinnacle Health System, Harrisburg, Pa.



Copyright © 2004 by the American Academy of Family Physicians.
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