epleronone (Inspra)
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Indications
- hypertension
- 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][7][8])
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]
Dosage
* 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)
- check serum K+ & renal function tests after starting moderate CYP3A4 inhibitor (see contraindications)[4]
- blood pressure
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 adverse effects of renin-angiotensin-aldosterone system inhibitors (RAAS inhibitors)
- drug adverse effects of diuretics
- drug adverse effects of antihypertensive agents
Drug interactions
- other K+-sparing diuretics (avoid)
- K+ supplements (avoid)
- other drugs the increase serum K+
- cyt P450 3A4 inhibitors
- drug interaction(s) SGLT2 inhibitors (flozins) with diuretics
- drug interaction(s) of calcineurin inhibitors with ACE inhibitors
- drug interaction(s) of calcineurin inhibitors with ARBs
- drug interaction(s) of diuretics in combination with Zn+2
- drug interaction(s) of antiarrhythmic agents in combination with diuretics
- drug interaction(s) of calcium channel blockers with diuretics
- drug interaction(s) of renin-angiotensin-aldosterone inhibitors with trimethoprim-sulfamethoxazole
- drug interaction(s) of spironolactone with potassium-sparing diuretics
- drug interaction(s) of ACE inhibitors with potassium-sparing diuretics
- drug interaction(s) of aldosterone antagonists with SGLT2-inhibitor
- 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 with aldosterone antagonis
- drug interaction(s) of NSAIDs, diuretics & angiotensin II receptor antagonists
- drug interaction(s) of NSAIDs, diuretics & ACE inhibitors
- drug interaction(s) of NSAIDs & antihypertensives
Mechanism of action
Notes
cost $99/30 tabs, 2005
More general terms
References
- ↑ Prescriber's Letter 10(11):62 2003
- ↑ Journal Watch 23(9):72, 2003 Pitt B et al, N Engl J Med 348(Apr 3):1309, 2003 http://content.nejm.org/cgi/content/abstract/348/14/1309 Jessup M, N Engl J Med 348(14):1380, 2003 http://content.nejm.org/cgi/content/abstract/348/14/1380
- ↑ LexiComp, Drug Information, 2005
- ↑ 4.0 4.1 4.2 Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260704&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 5.0 5.1 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#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260804&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 6.0 6.1 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: https://www.ncbi.nlm.nih.gov/pubmed/21073363 <Internet> http://dx.doi.org/10.1056/NEJMoa1009492
Armstrong PW. Aldosterone antagonists - Last man standing? N Engl J Med 2010 Nov 14; [e-pub ahead of print] <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21073364 <Internet> http://dx.doi.org/10.1056/NEJMe101254 - ↑ 7.0 7.1 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 Apr 3;348(14):1309-21. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12668699
- ↑ 8.0 8.1 Medical Knowledge Self Assessment Program (MKSAP) 16, American College of Physicians, Philadelphia 2012