Eplerenone

Eplerenone
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
Pronunciation /ɛpˈlɛrənoʊn/
Trade names Inspra
AHFS/Drugs.com monograph
MedlinePlus a603004
Pregnancy
category
Legal status
  • Schedule 4 (Aust), Rx only (US)
Routes of
administration		 oral
Pharmacokinetic data
Bioavailability 69%
Metabolism hepatic (CYP3A4)
Biological half-life 6-8 hours
Excretion 67% renal
32% biliary
Identifiers
CAS Number 107724-20-9 YesY
ATC code C03DA04
PubChem CID 5282131
IUPHAR/BPS 2876
DrugBank DB00700 YesY
ChemSpider 10203511 YesY
UNII 6995V82D0B YesY
KEGG D01115 YesY
ChEBI CHEBI:31547 YesY
ChEMBL CHEMBL1095097 YesY
Synonyms Epoxymexrenone, SC-66110
Chemical data
Formula C24H30O6
Molar mass 414.49
  (verify)

Eplerenone (INN) is a steroidal antimineralocorticoid of the spirolactone group that is 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, glucocorticoid, or estrogenic effects), and is specifically marketed for reducing cardiovascular risk in patients following myocardial infarction. It was 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

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]

Pharmacology

Eplerenone is an antimineralocorticoid, or an antagonist of the mineralocorticoid receptor (MR).[2][3] It has 10- to 20-fold lower affinity for the MR relative to spironolactone,[3] and is less potent in vivo as an antimineralocorticoid.[2] However, in contrast to spironolactone, eplerenone has little affinity for the androgen, progesterone, and glucocorticoid receptors.[2][3] In addition, it has more consistently observed non-genomic antimineralocorticoid effects relative to spironolactone (see membrane mineralocorticoid receptor).[2]

Adverse effects

Common adverse drug reactions (ADRs) associated with the use of eplerenone include: hyperkalaemia, hypotension, dizziness, altered renal function, and increased creatinine concentration.[4] 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.[5] 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

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

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,[6] potassium supplements and other potassium-sparing diuretics.

See also

References

  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. 1 2 3 4 Struthers A, Krum H, Williams GH (2008). "A comparison of the aldosterone-blocking agents eplerenone and spironolactone". Clin Cardiol 31 (4): 153–8. doi:10.1002/clc.20324. PMID 18404673.
  3. 1 2 3 Delyani, John A (2000). "Mineralocorticoid receptor antagonists: The evolution of utility and pharmacology". Kidney International 57 (4): 1408–1411. doi:10.1046/j.1523-1755.2000.00983.x. ISSN 0085-2538.
  4. ↑ Rossi S, editor.Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006
  5. ↑ 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.
  6. ↑ LoSalt Advisory Statement (PDF)


This article is issued from Wikipedia - version of the Friday, January 01, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.