Eplerenone

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Eplerenone
Eplerenon.svg
Systematic (IUPAC) name
pregn-4-ene-7,21-dicarboxylic acid, 9,11-epoxy-17-hydroxy-3-oxo, γ-lactone, methyl ester (7α, 11α, 17α)
Clinical data
Trade names Inspra
AHFS/Drugs.com monograph
MedlinePlus a603004
Pregnancy cat. B3 (Aust)
Legal status Schedule 4 (Aust), Rx only (US)
Routes oral
Pharmacokinetic data
Bioavailability 69%
Metabolism hepatic (CYP3A4)
Half-life 6-8 hours
Excretion 67% renal
32% biliary
Identifiers
CAS number 107724-20-9 YesY
ATC code C03DA04
PubChem CID 5282131
IUPHAR ligand 2876
DrugBank DB00700
ChemSpider 10203511 YesY
UNII 6995V82D0B YesY
KEGG D01115 YesY
ChEBI CHEBI:31547 YesY
ChEMBL CHEMBL1095097 YesY
Chemical data
Formula C24H30O6 
Mol. mass 414.49
 YesY (what is this?)  (verify)

Eplerenone (INN) /ɛpˈlɛrənn/ is an aldosterone antagonist used as an adjunct in the management of chronic heart failure. It is similar to the diuretic spironolactone, though it is much more selective for the mineralocorticoid receptor in comparison (i.e., does not possess any antiandrogen, progestogen, or estrogenic effects), and is specifically marketed for reducing cardiovascular risk in patients following myocardial infarction. It is marketed by Pfizer under the trade name Inspra. Eplerenone is a potassium-sparing diuretic, meaning that it helps the body get rid of water but still keep potassium.

Medical use[edit]

Eplerenone is specifically indicated for the reduction of risk of cardiovascular death in people with heart failure and left ventricular dysfunction within 3–14 days of an acute myocardial infarction, in combination with standard therapies and as treatment against hypertension. It appears equivalent to spironolactone but is much more expensive.[1]

Adverse effects[edit]

Common adverse drug reactions (ADRs) associated with the use of eplerenone include: hyperkalaemia, hypotension, dizziness, altered renal function, and increased creatinine concentration.[2] Eplerenone may have a lower incidence of sexual side effects such as feminization, gynecomastia, impotence, low sex drive and reduction of size of male genitalia.[3] Due to the high risk of elevated potassium levels in individuals taking eplerenone, the United States FDA suggests routine checks on the individual's potassium level to screen for hyperkalemia.

Contraindications[edit]

Eplerenone is contraindicated in patients with hyperkalaemia, severe renal impairment (creatinine Cl less than 30 ml/min), or severe hepatic impairment (Child-Pugh score C). The manufacturer of eplerenone also contraindicates ( relative C.I. ) concomitant treatment with ketoconazole, itraconazole or other potassium-sparing diuretics (though the manufacturer still considers taking these drugs to be absolute C.I.) Potential benefits should be weighted against possible risks.

Drug interactions[edit]

Eplerenone is primarily metabolised by the cytochrome P450 enzyme CYP3A4. Thus the potential exists for adverse drug interactions with other drugs that induce or inhibit CYP3A4. Specifically, the concomitant use of the CYP3A4 potent inhibitors ketoconazole and itraconazole is contraindicated. Other CYP3A4 inhibitors including erythromycin, saquinavir, and verapamil should be used with caution. Other drugs that increase potassium concentrations may increase the risk of hyperkalaemia associated with eplerenone therapy, including salt substitutes,[4] potassium supplements and other potassium-sparing diuretics.

Lab Synthesis[edit]

Eplerenone synth.png

Steroidal, Aldosterone Antagonists: Increased selectivity of 9α,11-epoxy derivatives. doi:10.1002/hlca.19970800220. 

See also[edit]

References[edit]

  1. ^ Chatterjee, S; Moeller, C; Shah, N; Bolorunduro, O; Lichstein, E; Moskovits, N; Mukherjee, D (August 2012). "Eplerenone is not superior to older and less expensive aldosterone antagonists.". The American Journal of Medicine 125 (8): 817–25. doi:10.1016/j.amjmed.2011.12.018. PMID 22840667. 
  2. ^ Rossi S, editor.Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006
  3. ^ Craft, Jennifer (April 2004). "Eplerenone". Proc (Bayl Univ Med Cent); Eplerenone (Inspra), a new aldosterone antagonist for the treatment of systemic hypertension and heart failure (Pub MedCentral) 17 (2): 217–20. PMC 1200656. PMID 16200104. 
  4. ^ LoSalt Advisory Statement (PDF)