Eplerenone

Source: Wikipedia, the free encyclopedia.
Eplerenone
Clinical data
Pronunciation/ɛpˈlɛrənoʊn/
Trade namesInspra, Epnone, Dosterep
Other namesSC-66110; CGP-30083; 9-11α-Epoxymexrenone; 9,11α-Epoxy-7α-methoxycarbonyl-3-oxo-17α-pregn-4-ene-21,17-carbolactone
AHFS/Drugs.comMonograph
MedlinePlusa603004
Pregnancy
category
  • AU: B3
Routes of
administration		By mouth (tablets)
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability~70%[2]
Protein binding~50% (33–60%) (primarily to α1-acid glycoprotein)[2][3]
MetabolismLiver (CYP3A4)[2][3]
Metabolites6β-OH-EPL, 6β,21-OH-EPL, 21-OH-EPL, 3α,6β-OH-EPL[2] (All inactive)[2]
Elimination half-life4–6 hours[4]
ExcretionUrine (67%), feces (32%)[5]
Identifiers
  • methyl (4aS,4bR,5aR,6aS,7R,9aS,9bR,10R)-4a,6a-dimethyl-2,5'-dioxo-2,4,4',4a,5',5a,6,6a,8,9,9a,9b,10,11-tetradecahydro-3H,3'H-spiro[cyclopenta[7,8]phenanthro[4b,5-b]oxirene-7,2'-furan]-10-carboxylate
JSmol)
  • COC(=O)[C@@H]4C\C1=C\C(=O)CC[C@]1(C)[C@@]65O[C@@H]6C[C@@]3(C)[C@@H](CC[C@]23CCC(=O)O2)[C@H]45
  • InChI=1S/C24H30O6/c1-21-7-4-14(25)10-13(21)11-15(20(27)28-3)19-16-5-8-23(9-6-18(26)30-23)22(16,2)12-17-24(19,21)29-17/h10,15-17,19H,4-9,11-12H2,1-3H3/t15-,16+,17-,19+,21+,22+,23-,24-/m1/s1 checkY
  • Key:JUKPWJGBANNWMW-VWBFHTRKSA-N checkY
  (verify)

Eplerenone, sold under the brand name Inspra, is an

antimineralocorticoid of the spirolactone group and a selective aldosterone receptor antagonist (SARA).[6] Eplerenone is more selective than spironolactone at the mineralocorticoid receptor relative to binding at androgen, progestogen, glucocorticoid, or estrogen
receptors.

Medical uses

Heart failure

Eplerenone reduces risk of death in patients with heart failure,[7] particularly in patients with recent myocardial infarction (heart attack).[8]

Hypertension

Eplerenone lowers blood pressure in patients with primary hypertension.[9] Eplerenone also reduces arterial stiffness and vascular endothelial dysfunction.[10]

For persons with resistant hypertension, eplerenone is safe and effective for reducing blood pressure,[11] particularly in persons with resistant hypertension due to hyperaldosteronism.[12][13]

Central serous chorioretinopathy

Eplerenone is often prescribed for people with central serous chorioretinopathy (CSC). However, the most recent and largest randomized controlled trial showed that eplerenone has no significant effect on chronic CSC that has been untreated for four months.[14][15]

Adverse effects

Common

impotence, low sex drive and reduction of size of male genitalia.[17] This is because other antimineralocorticoids have structural elements of the progesterone molecule, causing progestogenic and antiandrogenic outcomes.[4] When considering taking these medicines, it is important to note the variations in their ability to offset the nongenomic effects of aldosterone.[4]

Currently, there is not enough evidence available from the randomized controlled trials on side effects of eplerenone to do a benefit versus risk assessment in people with primary hypertension.[18]

Interactions

Eplerenone is primarily metabolized 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 hyperkalemia associated with eplerenone therapy, including salt substitutes,[19] potassium supplements and other potassium-sparing diuretics
.

Pharmacology

Eplerenone is an

affinity for the MR relative to spironolactone,[20] and is less potent in vivo as an antimineralocorticoid.[4] However, in contrast to spironolactone, eplerenone has little affinity for the androgen, progesterone, and glucocorticoid receptors.[20][4] It also has more consistently observed non-genomic antimineralocorticoid effects relative to spironolactone (see membrane mineralocorticoid receptor).[4] Eplerenone differs from spironolactone in its extensive metabolism, with a short half-life and inactive metabolites.[4]

Eplerenone seems to be about 50 to 75% as potent as spironolactone as an antimineralocorticoid.[23] Hence, 25 mg/day spironolactone may be equivalent to approximately 50 mg/day eplerenone.[24]

Regulatory and Patent History

Eplerenone was patented in 1983 and approved for medical use in the United States in 2002.[25][22] Eplerenone is currently approved for sale in Canada, the US, EU, Netherlands and Japan.[22] Eplerenone costs an estimated $2.93 per day when treating congestive heart failure and $5.86 per day when treating hypertension.[17]

See also

References

  1. FDA
    . Retrieved 22 Oct 2023.
  2. ^
    ISBN 978-1-60913-345-0
    .
  3. ^
    S2CID 21437788
    .
  4. ^
    PMID 18404673
    .
  5. ISBN 978-1-57340-221-7
    .
  6. PMID 11607037
    .
  7. S2CID 198999728
    .
  8. S2CID 219936888
    .
  9. PMID 28245343
    .
  10. PMID 33461316
    .
  11. PMID 25801902
    .
  12. S2CID 218670505
    .
  13. PMID 28449833
    .
  14. S2CID 241440498
    .
  15. PMID 31982075
    .
  16. ISBN 978-0-9757919-2-9
    .
  17. ^
    PMID 16200104
    .
  18. PMID 28245343
    .
  19. ^ LoSalt Advisory Statement Archived 2005-12-10 at the Wayback Machine (PDF)
  20. ^
    PMID 10760075
    .
  21. S2CID 13904574
    .
  22. ^ a b c "Inspra (Eplerenone)". Drug Development Technology. Retrieved 2016-04-19.
  23. PMID 18404673
    .
  24. ISBN 978-0-7295-7927-8
    .
  25. ISBN 9783527607495
    .


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