Eplerenone

From Anvita Health Wiki

Contents 1 Indications 2 Contraindications 3 Dosage 4 Pharmacokinetics 5 Monitor 6 Adverse-effects 7 Drug-interactions 8 Mechanism-of-action 9 Notes 10 More General Terms 11 Internet Database 12 References

Indications

• post myocardial infarction
• heart failure ( left ventricular systolic dysfunction)*
• for use in combination with

• ACE inhibitor or angiotensin receptor blocker ( ARB)
• other diuretic (i.e. loop diuretic)
• beta-blocker

• * improves mortality in patients after myocardial infarction with heart failure & left ventricular ejection fraction < 40% (11.85 vs 13.6%, 12.5% vs 15.5% [6]) (2 different studies)

Contraindications

• renal failure

• serum creatinine > 2.5 mg/dL (men) > 2.0 mg/dL (women) [5]
• creatinine clearance < 30 mL/min

• concurrent administration of strong CYP3A4 inhibitor ( clarithromycin, ketoconazole) [4]
  

• pregnancy category = b

Dosage

• CHF: start 25 mg PO QD; max 50 mg QD
• hypertension: start 50 mg QD
• max dose 50 mg BID*

• * Doses > 100 mg associated with increased risk of hyperkalemia without additional clinical benefit

Pharmacokinetics

• peak plasma levels in 1.5 hours
• may take 4 weeks for full therapeutic effect
• volume of distribution 43-90 L
• protein-binding 50% (primarily alpha-1 acid glycoprotein)
• metabolized by cyt P450 3A4, metabolites inactive
• elimination 1/2life of 4-6 hours
• 5% eliminated unchanged in the urine

• Tabs: 25, 50 mg.
  

Monitor

• serum K+ (one week, one month & periodically after starting or changing dose)

• lower the dose if [K+] > 5.5 meq/L
• withhold dose if [K+] > 6.0 meq/L

• check serum K+ & renal function tests after starting moderate CYP3A4 inhibitor (see contraindications) [4]
• blood pressure
  
• monitor with potassium-sparing diuretics

Adverse-effects

• hyperkalemia
• less likely to cause gynecomastia or impotence than spironolactone
• hypertriglyceridemia (1-15%) dose-related
• diarrhea (2%)
• flu-like syndrome (2%)
• albuminuria (1%)
• cough (2%)

Drug-interactions

• other K+-sparing diuretics (avoid)
• K+ supplements (avoid)
• other drugs the increase serum K+

• ACE inhibitors, beta blockers

• cyt P450 3A4 inhibitors

• ketoconazole, itraconazole, nefazodone, clarithromycin ritonavir
  

• drug interaction(s) of antiarrhythmic agents in combination with diuretics
• drug interaction(s) of renin-angiotensin inhibitors with trimethoprim-sulfamethoxazole
• drug interaction(s) of spironolactone with potassium-sparing diuretics
• drug interaction(s) of diuretics with angiotensin II receptor antagonists
• drug interaction(s) of diuretics with ACE inhibitors
• drug interaction(s) of eplerenone with nelfinavir
• drug interaction(s) of eplerenone with ritonavir
• drug interaction(s) of eplerenone with clarithromycin
• drug interaction(s) of eplerenone with intraconazole
• drug interaction(s) of eplerenone with ketoconazole
• drug interaction(s) of NSAIDs, diuretics & angiotensin II receptor antagonists
• drug interaction(s) of NSAIDs, diuretics & ACE inhibitors

Mechanism-of-action

• aldosterone antagonist
• see spironolactone

Notes

• cost $99/30 tabs, 2005

More General Terms

• K+ sparing diuretic
• aldosterone receptor antagonist (aldosterone antagonist)

Internet Database

PubChem: 5282131
PubChem: 150310
PubChem: 443872

References

1. Prescriber's Letter 10(11):62 2003
2. Journal Watch 23(9):72, 2003 Pitt B et al, N Engl J Med 348(Apr 3):1309, 2003 [1] Jessup M, N Engl J Med 348(14):1380, 2003 [2]
3. LexiComp, Drug Information, 2005
4. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Detail-Document#: [3] (subscription needed) [4]
5. Prescriber's Letter 17(8): 2010 COMMENTARY: Eplerenone (Inspra) for Mild Systolic Heart Failure GUIDELINES: Diagnosis and Management of Heart Failure in Adults (ACC/AHA, 2009 Update) Detail-Document#: [5] (subscription needed) [6]
6. Zannad F et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2010 Nov 14; [e-pub ahead of print] <PubMed> PMID: [7] <Internet> [8]
   - Armstrong PW. Aldosterone antagonists - Last man standing? N Engl J Med 2010 Nov 14; [e-pub ahead of print] <PubMed> PMID: [9] <Internet> [10]

epleronone (Inspra)