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Eplerenone

Class: Mineralocorticoid (Aldosterone) Receptor Antagonists
VA Class: CV704
Chemical Name: 9,11α-Epoxy-17-hydroxy-3-oxo-17α-pregn-4-ene-7α,21-dicarboxylic acid, γ-lactone, methyl ester
Molecular Formula: C24H30O6
CAS Number: 107724-20-9
Brands: Inspra

Medically reviewed by Drugs.com. Last updated on Apr 15, 2019.

Introduction

Relatively selective mineralocorticoid (aldosterone) receptor antagonist.1 2 3 10 11

Uses for Eplerenone

Heart Failure after Acute MI

Used to reduce the risk of mortality following acute MI in clinically stable patients with left ventricular systolic dysfunction (i.e., left ventricular ejection fraction [LVEF] ≤40%) and heart failure.1 17 21 524

Therapy with an aldosterone antagonist (i.e., eplerenone or spironolactone) recommended by ACCF and AHA to reduce morbidity and mortality following acute MI in patients with reduced LVEF (≤40%) who develop symptoms of heart failure or who have a history of diabetes mellitus, unless contraindicated.524

Chronic Heart Failure

Has been used in the management of chronic heart failure (NYHA class II–IV) with reduced ejection fraction in conjunction with standard therapy for heart failure to increase survival and reduce heart failure-related hospitalizations.524 700 721

ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend the addition of an aldosterone antagonist (i.e., eplerenone or spironolactone) in selected patients with heart failure and reduced LVEF who are already receiving an agent to inhibit the renin-angiotensin-aldosterone (RAA) system (e.g., ACE inhibitor, angiotensin II receptor antagonist, angiotensin receptor-neprilysin inhibitor [ARNI]) and a β-blocker; careful patient selection required to minimize the risk of hyperkalemia and renal insufficiency.524 700

Hypertension

Management of hypertension.1 2 3 4 10 11 24 1200

Used as monotherapy or in combination with other classes of antihypertensive agents.1 2 4 10 11

Not considered a preferred agent for initial management of hypertension according to current evidence-based hypertension guidelines, but may be used as add-on therapy if BP not adequately controlled with the recommended antihypertensive drug classes (i.e., ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, thiazide diuretics).501 502 503 504 1200

Some experts state that eplerenone may be useful for the management of resistant hypertension in patients with type 2 diabetes mellitus when added to an existing treatment regimen consisting of a renin-angiotensin system inhibitor (e.g., ACE inhibitor, angiotensin II receptor antagonist), diuretic, and calcium-channel blocker.1215

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).501 502 503 504 515 1200 1201

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension.1200 (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

Table 1. ACC/AHA BP Classification in Adults1200

Category

SBP (mm Hg)

DBP (mm Hg)

Normal

<120

and

<80

Elevated

120–129

and

<80

Hypertension, Stage 1

130–139

or

80–89

Hypertension, Stage 2

≥140

or

≥90

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP.1200 However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.501 503 504 505 506 507 508 515 523 526 530 1200 1201 1207 1209 1222 1223 1229

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) of <130/80 mm Hg in all adults, regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.1200 In addition, an SBP goal of <130 mm Hg generally is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg.1200 These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.1200 1202 1210

Other hypertension guidelines generally based target BP goals on age and comorbidities.501 504 536 Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk, and have used higher BP thresholds and target BPs in elderly patients501 504 536 compared with those recommended by the 2017 ACC/AHA hypertension guideline.1200

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the 2017 ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.1222 1223 1224 1229

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient's BP treatment goal.1200 1220 1229

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors.1200 1207 ASCVD risk assessment is recommended by ACC/AHA for all adults with hypertension.1200

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).1200

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.1200

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg.1200 Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.502 1200

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP.1200 Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.1200

Eplerenone Dosage and Administration

General

  • Measure serum potassium concentrations prior to initiation of therapy, within the first week, and at 1 month after initiation of therapy or dosage adjustment.1

  • Monitor serum potassium concentrations periodically thereafter, and modify drug dosage accordingly.1 (See Table: Dosage Modification in Heart Failure for Serum Potassium Concentrations under Dosage and Administration.)

Monitoring and BP Treatment Goals

  • Monitor BP regularly (i.e., monthly) during therapy and adjust dosage of the antihypertensive drug until BP controlled.1200

  • If unacceptable adverse effects occur, discontinue drug and initiate another antihypertensive agent from a different pharmacologic class.1200 1216

  • Assess patient's renal function and electrolytes 2–4 weeks after initiation of diuretic therapy.1200

  • If adequate BP response not achieved, either increase dosage of the drug or add another drug with demonstrated benefit and preferably a complementary mechanism of action (e.g., ACE inhibitor, angiotensin II receptor antagonist, calcium-channel blocker, thiazide diuretic).1200 1216 Many patients will require ≥2 drugs from different pharmacologic classes to achieve BP goal.1200 1216 1220

Administration

Oral Administration

Administer orally1 2 3 11 without regard to meals.1

Dosage

Adults

Heart Failure after Acute MI
Oral

Initially, 25 mg once daily.1 Titrate dosage as tolerated to a target dosage of 50 mg once daily, preferably within 4 weeks of initiation of therapy in patients without hyperkalemia (defined as serum potassium concentrations ≥5.5 mEq/L).1

Dosage Modification in Heart Failure for Serum Potassium Concentrations1

Serum Potassium (mEq/L)

Dosage Adjustment

<5

In those receiving 25 mg every other day, increase to 25 mg daily; in those receiving 25 mg daily, increase to 50 mg daily

5–5.4

None

5.5–5.9

In those receiving 50 mg daily, decrease to 25 mg daily; in those receiving 25 mg daily, decrease to 25 mg every other day; in those receiving 25 mg every other day, withhold therapy

≥6

Withhold

ACCF/AHA recommendation: Hold eplerenone therapy if serum potassium >5.5 mEq/L or renal function worsens; consider resuming therapy at reduced dosage after resolution (for ≥72 hours) of hyperkalemia (serum potassium <5 mEq/L) and renal insufficiency.524

Hypertension
Oral

Initially, 50 mg once daily.1 3 8 If BP is not adequately controlled after 4 weeks, increase dosage to 50 mg twice daily.1

Some experts state usual dosage range is 50–100 mg daily, given in 1 dose or 2 divided doses.1200

In hypertensive patients currently receiving therapy with weak inhibitors of CYP3A4 (e.g., erythromycin, saquinavir, verapamil, fluconazole), reduce the initial dosage to 25 mg once daily.1 3 8

Chronic Heart Failure
Oral

Has been administered at an initial dosage of 25 mg once daily and increased after 4 weeks of therapy to 50 mg once daily in patients with serum potassium ≤5 mEq/L and adequate renal function.524 721

Hold eplerenone therapy if serum potassium >5.5 mEq/L or renal function worsens; consider resuming therapy at reduced dosage after resolution (for ≥72 hours) of hyperkalemia (serum potassium <5 mEq/L) and renal insufficiency.524

Prescribing Limits

Adults

Hypertension
Oral

50 mg twice daily.1 No additional benefit from higher dosages (>100 mg daily) and such dosages have been associated with increased risk of hyperkalemia.1

Special Populations

Hepatic Impairment

No adjustment in the initial dosage is necessary in those with mild-to-moderate hepatic impairment.1 21 (See Hepatic Impairment under Cautions.)

Renal Impairment

Heart failure patients with eGFR 30–49 mL/minute per 1.73 m2: Initially, 25 mg once every other day; maintenance dosage of 25 mg once daily (after 4 weeks of therapy and if serum potassium ≤5 mEq/L).524

Heart failure patients with eGFR <30 mL/minute per 1.73 m2: Use is potentially harmful.524

Geriatric Patients

No adjustment in the initial dosage is necessary.1 21

Cautions for Eplerenone

Contraindications

  • Serum potassium concentrations >5.5 mEq/L at initiation of therapy.1

  • Clcr ≤ 30 mL/minute.1

  • Concomitant therapy with potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir, any agent described as a potent CYP3A4 inhibitor in its prescribing information).1 4

  • In hypertensive patients having type 2 diabetes mellitus with microalbuminuria.1

  • In hypertensive patients with Scr >2 or 1.8 mg/dL in males or females, respectively.1

  • In hypertensive patients with Clcr <50 mL/minute.1

  • In hypertensive patients receiving potassium supplements or potassium-sparing diuretics (e.g., amiloride, spironolactone, triamterene).1 4 8

Warnings/Precautions

Warnings

Hyperkalemia

Most serious risk associated with therapy is hyperkalemia (serum potassium >5.5 mEq/L).1 Hyperkalemia may cause serious, sometimes fatal, cardiac arrhythmias.1 11

Increased risk of hyperkalemia in patients with impaired renal function or diabetes mellitus and in patients receiving concurrent agents affecting the RAA system (e.g., ACE inhibitors, angiotensin II receptor antagonists).1 2 4 8 11 13 21

Monitor serum potassium concentrations periodically.1 21 Some experts recommend checking serum potassium and renal function within 2–3 days and again at 7 days after initiation of an aldosterone antagonist; perform subsequent monitoring as needed based upon the stability of renal function and fluid status, but monitor at least monthly for the first 3 months and every 3 months thereafter.524 (See Table: Dosage Modification in Heart Failure for Serum Potassium Concentrations under Dosage and Administration.)1

Specific Populations

Pregnancy

Category B.

Lactation

Distributed into milk in animals.1 Discontinue nursing or the drug.1

Pediatric Use

The manufacturer states that in hypertensive pediatric patients 4–16 years of age, eplerenone in dosages up to 100 mg daily did not lower BP effectively.1 In safety studies in patients 5–17 years of age who received eplerenone for up to 1 year, the incidence of adverse effects was similar to that in studies in adults.1 Data on safety and efficacy of eplerenone therapy are lacking in hypertensive patients <4 years of age because the drug did not demonstrate efficacy in older pediatric patients.1

Safety and efficacy of eplerenone not established in pediatric patients with heart failure.1

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.1 Geriatric patients ≥75 years of age with CHF following an acute MI did not benefit from the addition of eplerenone to standard medical therapy.1 Because of the greater frequency of decreased renal function, the incidence of hyperkalemia may be increased in the elderly.1 (See Renal Impairment under Cautions.)

Hepatic Impairment

Safety and efficacy not established in patients with severe hepatic impairment.1 Serum potassium concentrations not affected in patients with mild-to-moderate hepatic impairment.1

Renal Impairment

Use with caution in patients with CHF following an acute MI, who have renal impairment (i.e., Scr >2 or 1.8 mg/dL in males or females, respectively, or Clcr ≤50 mL/minute) or those with diabetes mellitus (including those with proteinuria).1

Drug contraindicated in hypertensive patients with Scr >2 or 1.8 mg/dL in males or females, respectively, and in those hypertensive patients with Clcr <50 mL/minute.1

Black Patients

Initial BP reduction may be smaller in black patients compared with nonblack patients;1 such difference does not appear to occur during continued therapy.2

Common Adverse Effects

In patients with CHF following MI: hyperkalemia,1 17 increased Scr,1 urinary tract disorders,17 adverse CNS effects,17 adverse GI effects.17

In patients with hypertension: dizziness, fatigue, flu-like symptoms, cough, diarrhea, abdominal pain, hyperkalemia, decreased serum sodium concentrations, abnormal vaginal bleeding, gynecomastia, hypercholesterolemia, hypertriglyceridemia, mastodynia, albuminuria.1

Interactions for Eplerenone

Metabolized by CYP3A4 isoenzyme.1

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction (altered plasma eplerenone concentrations) with drugs that induce or inhibit CYP3A4.1

Does not inhibit or induce the CYP isoenzymes 1A2, 3A4, 2C19, 2C9, or 2D6, suggesting that the drug is unlikely to alter the pharmacokinetics of drugs metabolized by these enzymes.1 21

Specific Drugs and Food1

Drug or Food

Interaction

Comments

ACE inhibitors

Possible increased serum potassium concentrations, hyperkalemia

Amiloride

Increased risk for hyperkalemia

Concomitant use contraindicated in patients with hypertension

Amiodarone

Pharmacokinetic interaction unlikely

Amlodipine

Pharmacokinetic interaction unlikely

Angiotensin II receptor antagonists

Possible increased serum potassium concentrations, hyperkalemia

Antacids (e.g., aluminum- and magnesium-containing)

Pharmacokinetic interaction unlikely

Astemizole

Pharmacokinetic interaction unlikely

Chlorzoxazone

Pharmacokinetic interaction unlikely

Cisapride

Pharmacokinetic interaction unlikely

Clarithromycin

Increased plasma concentrations of eplerenone

Concomitant use contraindicated

Cyclosporine

Pharmacokinetic interaction unlikely

Dexamethasone

Pharmacokinetic interaction unlikely

Dextromethorphan

Pharmacokinetic interaction unlikely

Diclofenac

Pharmacokinetic interaction unlikely

Digoxin

Pharmacokinetic interaction unlikely

Erythromycin

Increased plasma concentrations of eplerenone

Reduce eplerenone dosage (see Dosage: Hypertension, under Dosage and Administration)

Ethinyl estradiol

Pharmacokinetic interaction unlikely

Fluconazole

Increased plasma concentrations of eplerenone

Reduce eplerenone dosage (see Dosage: Hypertension, under Dosage and Administration)

Fluoxetine

Pharmacokinetic interaction unlikely

Glyburide

Pharmacokinetic interaction unlikely

Grapefruit juice

Increased eplerenone exposure

Hormonal contraceptives (norethindrone/ethinyl estradiol)

Pharmacokinetic interaction unlikely

Itraconazole

Increased plasma concentrations of eplerenone

Concomitant use contraindicated

Ketoconazole

Increased plasma concentrations of eplerenone

Concomitant use contraindicated

Lithium

Possible increased serum lithium concentrations resulting in lithium toxicity;1 such interaction observed with concomitant administration of diuretics and/or ACE inhibitors and lithium1 5 7 14 15

If used concomitantly, frequently monitor serum lithium concentrations1

Losartan

Pharmacokinetic interaction unlikely

Lovastatin

Pharmacokinetic interaction unlikely

Midazolam

Pharmacokinetic interaction unlikely

Mephobarbital

Pharmacokinetic interaction unlikely

Methylphenidate

Pharmacokinetic interaction unlikely

Methylprednisolone

Pharmacokinetic interaction unlikely

Metoprolol

Pharmacokinetic interaction unlikely

Nefazodone

Increased plasma concentrations of eplerenone

Concomitant use contraindicated

Nelfinavir

Increased plasma concentrations of eplerenone

Concomitant use contraindicated

Nifedipine

Pharmacokinetic interaction unlikely

NSAIAs

Possible decreased antihypertensive effect and/or severe hyperkalemia in patients with impaired renal function

Phenytoin

Pharmacokinetic interaction unlikely

Potassium-sparing agents or potassium supplements

Possible increased risk of hyperkalemia 1 4 21

Ritonavir

Increased plasma concentrations of eplerenone

Concomitant use contraindicated

Saquinavir

Increased plasma concentrations of eplerenone

Reduce eplerenone dosage (see Dosage: Hypertension, under Dosage and Administration)

St. John's wort

Decreased eplerenone AUC

Simvastatin

Pharmacokinetic interaction unlikely

Spironolactone

Increased risk for hyperkalemia

Concomitant use contraindicated in patients with hypertension

Tolbutamide

Pharmacokinetic interaction unlikely

Triamterene

Increased risk for hyperkalemia

Concomitant use contraindicated in patients with hypertension

Triazolam

Pharmacokinetic interaction unlikely

Troleandomycin

Increased plasma concentrations of eplerenone

Concomitant use contraindicated

Verapamil

Increased plasma concentrations of eplerenone

Reduce eplerenone dosage (see Dosage: Hypertension, under Dosage and Administration)

Warfarin

Pharmacokinetic interaction unlikely

Eplerenone Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability 69% (100-mg oral tablet).1

Peak plasma concentrations usually attained within 1.5–2 hours.1 Steady-state plasma concentrations attained within 2 days.1

Onset

During chronic therapy, hypotensive effect apparent within 2 weeks and maximum antihypertensive effect generally achieved after 4 weeks.1

Duration

In patients not receiving other antihypertensive drugs, BP may return to pretreatment levels within 1 week following discontinuance.1 21

Food

Food does not appear to affect absorption.1

Special Populations

In geriatric patients ≥65 years of age at steady state, peak plasma concentrations and AUC increased by 22 and 45%, respectively, compared with younger adults (18–45 years old).1

In geriatric black patients at steady state, peak plasma concentrations and AUC were 19 and 26% lower, respectively, than in geriatric white patients.1 25

In patients with severe renal impairment at steady state, peak plasma concentration and AUC were increased by 24 and 38%, respectively,1 while in those undergoing hemodialysis, peak plasma concentrations and AUC were decreased by 3 and 26%, respectively.1

In patients with moderate (Child-Pugh class B) hepatic impairment at steady state, peak plasma concentrations and AUC were increased by 3.6 and 42%, respectively, compared with healthy individuals.1

In patients with heart failure (NYHA class II–IV) at steady state, peak plasma concentrations and AUC increased by 30 and 38%, respectively, compared with healthy individuals.1

Distribution

Extent

Apparent volume of distribution at steady state is 42–90 L.1

Plasma Protein Binding

50% (mainly α1-acid glycoproteins).1 Does not bind preferentially to RBCs.1

Distributed into milk in rats; not known whether distributed into human milk.1

Elimination

Metabolism

Metabolized to inactive metabolites principally by CYP3A4 isoenzyme.1 2

Elimination Route

Approximately 67 and 32% of a dose is excreted in urine and feces, respectively, principally as metabolites.1 2

Half-life

3–6 hours.1

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).1

Actions

  • Inhibits physiologic effects of aldosterone.1 2 3 4 10

  • Produces sustained increases in plasma renin and serum aldosterone concentrations, reflecting the inhibition of the negative feedback of aldosterone on renin secretion.1 2 3 10 11

  • Some of the antihypertensive effects may be related to restoration of endothelial function by increasing the release of nitric oxide, which results in vasodilation.2 9 12

  • Reduces coronary vascular inflammation,17 18 the risk of subsequent development of interstitial myocardial and coronary perivascular fibrosis,2 17 18 19 20 cardiac hypertrophy,2 20 and/or ventricular remodeling.2 17 20

Advice to Patients

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of not using concomitant potassium supplements, salt substitutes containing potassium, potassium-sparing diuretics (amiloride, triamterene, spironolactone), or potent inhibitors of liver enzymes without consulting a clinician.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Eplerenone

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

25 mg*

Eplerenone Tablets

Inspra

Pfizer

50 mg*

Eplerenone Tablets

Inspra

Pfizer

AHFS DI Essentials™. © Copyright 2019, Selected Revisions April 15, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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2. Zillich AJ, Carter BL. Eplerenone—a novel selective aldosterone blocker. Ann Pharmacother. 2002; 36:1567-76. http://www.ncbi.nlm.nih.gov/pubmed/12243608?dopt=AbstractPlus

3. Weinberger MH, Roniker B, Krause SL et al.. Eplerenone, a selective aldosterone blocker, in mild-to-moderate hypertension. Am J Hypertens. 2002; 15:709-16. http://www.ncbi.nlm.nih.gov/pubmed/12160194?dopt=AbstractPlus

4. Sica DA. Current concepts of pharmacotherapy in hypertension. Eplerenone: a new aldosterone receptor antagonist— are the FDAs restrictions appropriate? J Clin Hypertens (Greenwich). 2002; 4:441-5.

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6. Johnson AG, Seideman P. Ray RO. Adverse drug interactions with nonsteroidal anti-inflammatory drugs (NSAIDS): Recognition, management and avoidance. Drug Saf. 1993; 8:99-127. http://www.ncbi.nlm.nih.gov/pubmed/8452660?dopt=AbstractPlus

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8. Schepkens H, Vanholder R, Billiouw JM et al. Life-threatening hyperkalemia during combined therapy with angiotensin-converting enzyme inhibitors and spironolactone: an analysis of 25 cases. Am J Med. 2001; 110:438-41. http://www.ncbi.nlm.nih.gov/pubmed/11331054?dopt=AbstractPlus

9. Quaschning T, Ruschitzka F, Shaw S et al. Aldosterone receptor antagonism normalizes vascular function in liquorice-induced hypertension. Hypertension. 2001; 37(pt. 2):801-5. http://www.ncbi.nlm.nih.gov/pubmed/11230376?dopt=AbstractPlus

10. Liew D, Krum H. The role of aldosterone recptor blockade in the management of cardiovascular disease. Curr Opin Investig Drugs. 2002; 3:1468-73. http://www.ncbi.nlm.nih.gov/pubmed/12431020?dopt=AbstractPlus

11. Krum H, Nolly H, Workman D et al. Efficacy of eplerenone added to renin-angiotensin blockade in hypertensive patients. Hypertension. 2002; 40:117-23. http://www.ncbi.nlm.nih.gov/pubmed/12154100?dopt=AbstractPlus

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17. Pitt B, Remme W, Zannad F et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003; 348:1309-21. http://www.ncbi.nlm.nih.gov/pubmed/12668699?dopt=AbstractPlus

18. Brown NJ. Eplerenone: cardiovascular protection. Circulation. 2003; 107:2512-8. http://www.ncbi.nlm.nih.gov/pubmed/12756192?dopt=AbstractPlus

19. Delyani JA, Robinson EL, Rudolph AE. Effect of a selective aldosterone receptor antagonist in myocardial infarction. Am J Physiol Heart Circ Physiol. 2001; 50:H647-54.

20. Suzuki G, Morita H, Mishima T et al. Effects of long-term monotherapy with eplerenone, a novel aldosterone blocker, on progression of left ventricular dysfunction and remodeling in dogs with heart failure. Circulation. 2002; 106:2967-72. http://www.ncbi.nlm.nih.gov/pubmed/12460880?dopt=AbstractPlus

21. Pfizer, New York, NY: Personal communication.

23. Vasan RS, Evans JC, Larson MG et al. Serum aldosterone and the incidence of hypertension in nonhypertensive persons. N Engl J Med. 2004; 351:33-41. http://www.ncbi.nlm.nih.gov/pubmed/15229305?dopt=AbstractPlus

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