Spironolactone

Not to be confused with Spirolactone.

Spironolactone
Skeletal formula of spironolactone
Ball-and-stick model of the spironolactone molecule
Clinical data
Pronunciation/ˌspaɪroʊnoʊˈlæktoʊn/ SPY-roh-noh-LAK-tone,[1] /ˌspɪəroʊnoʊˈlæktoʊn/ SPEER-oh-noh-LAK-tone[2]
Trade namesAldactone, others
Other namesSC-9420; NSC-150339; 7α-Acetylthiospirolactone; 7α-Acetylthio-17α-hydroxy-3-oxopregn-4-ene-21-carboxylic acid γ-lactone
AHFS/Drugs.comMonograph
MedlinePlusa682627
License data
Pregnancy
category
Routes of
administration		By mouth,[4] topical[5]
Drug classAntimineralocorticoid; Steroidal antiandrogen
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability60–90%[11][12][13]
Protein bindingSpironolactone: 88% (to albumin and AGPTooltip alpha-1-acid glycoprotein)[14]
Canrenone: 99.2% (to albumin)[14]
MetabolismLiver, others:
• Deacetylation via CESTooltip carboxylesterase
• S-Oxygenation via FOMTooltip flavin-containing monooxygenase
• S-Methylation via TMTTooltip thiol S-methyltransferase
• Dethioacetylation
• Hydroxylation via CYP3A4
• Lactone hydrolysis via PON3[11][12][17][18][19][20][21]
Metabolites7α-TSTooltip 7α-Thiospironolactone, 7α-TMSTooltip 7α-thiomethylspironolactone, 6β-OH-7α-TMSTooltip 6β-hydroxy-7α-thiomethylspironolactone, canrenone, others[11][12][15]
(All three active)[16]
Elimination half-lifeSpironolactone: 1.4 hrs[11]
7α-TMSTooltip 7α-thiomethylspironolactone: 13.8 hours[11]
6β-OH-7α-TMSTooltip 6β-hydroxy-7α-thiomethylspironolactone: 15.0 hrs[11]
Canrenone: 16.5 hours[11]
ExcretionUrine, bile[12]
Identifiers
  • S-[(7R,8R,9S,10R,13S,14S,17R)-10,13-Dimethyl-3,5'-dioxospiro[2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-17,2'-oxolane]-7-yl] ethanethioate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.000.122 Edit this at Wikidata
Chemical and physical data
FormulaC24H32O4S
Molar mass416.58 g·mol−1
3D model (JSmol)
Melting point134 to 135 °C (273 to 275 °F)
  • O=C5O[C@@]4([C@@]3([C@H]([C@@H]2[C@H](SC(=O)C)C/C1=C/C(=O)CC[C@]1(C)[C@H]2CC3)CC4)C)CC5
  • InChI=1S/C24H32O4S/c1-14(25)29-19-13-15-12-16(26)4-8-22(15,2)17-5-9-23(3)18(21(17)19)6-10-24(23)11-7-20(27)28-24/h12,17-19,21H,4-11,13H2,1-3H3/t17-,18-,19+,21+,22-,23-,24+/m0/s1 checkY
  • Key:LXMSZDCAJNLERA-ZHYRCANASA-N checkY
  (verify)
Spironolactone 25 mg

Spironolactone, sold under the brand name Aldactone among others, is a diuretic medication primarily used to treat fluid build-up due to heart failure, liver scarring, or kidney disease.[4] It is also used in the treatment of high blood pressure, and low blood potassium that does not improve with supplementation, early puberty in boys, acne and excessive hair growth in women.[4][22][23] Spironolactone is taken by mouth.[4]

Common side effects include electrolyte abnormalities, particularly high blood potassium, nausea, vomiting, headache, rashes, and a decreased desire for sex.[4] In those with liver or kidney problems, extra care should be taken.[4] Spironolactone has not been well studied in pregnancy and should not be used to treat high blood pressure of pregnancy.[3] It is also a steroid that blocks the effects of the hormones aldosterone and, to a lesser degree, testosterone, causing some estrogen-like effects.[24][unreliable source?][25][26][unreliable medical source?][4][27] Spironolactone belongs to a class of medications known as potassium-sparing diuretics.[4]

Spironolactone was discovered in 1957, and was introduced in 1959.[28][29][30] It is on the World Health Organization's List of Essential Medicines.[31] It is available as a generic medication.[4] In 2022, it was the 52nd most commonly prescribed medication in the United States, with more than 12 million prescriptions.[32][33] Spironolactone has a history of use in the trans community.[34] Its use continues despite the rise of various accessible alternatives such as bicalutamide and cyproterone acetate with more precise action and less side effects.[24][25]

  1. ^ Loughlin KR, Generali JA (2006). The Guide to Off-label Prescription Drugs: New Uses for FDA-approved Prescription Drugs. Simon and Schuster. pp. 131–. ISBN 978-0-7432-8667-1. Archived from the original on 7 October 2022. Retrieved 6 November 2016.
  2. ^ Clark MA, Harvey RA, Finkel R, Rey JA, Whalen K (15 December 2011). Pharmacology. Lippincott Williams & Wilkins. pp. 286, 337. ISBN 978-1-4511-1314-3. Archived from the original on 7 October 2022. Retrieved 6 November 2016.
  3. ^ a b "Spironolactone Pregnancy and Breastfeeding Warnings". The American Society of Health-System Pharmacists. Archived from the original on 2 December 2015. Retrieved 29 November 2015.
  4. ^ a b c d e f g h i "Spironolactone". The American Society of Health-System Pharmacists. Archived from the original on 16 November 2015. Retrieved 24 October 2015.
  5. ^ Cite error: The named reference FARIDDiamanti-Kandarakis2009 was invoked but never defined (see the help page).
  6. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  7. ^ "Aldactone 25 mg Film-Coated TabletsSummary of Product Characteristics (SmPC)". (emc). 3 February 2022. Archived from the original on 6 October 2022. Retrieved 2 August 2023.
  8. ^ Cite error: The named reference Aldactone label was invoked but never defined (see the help page).
  9. ^ "Qaialdo EPAR". European Medicines Agency (EMA). 25 July 2023. Archived from the original on 27 July 2023. Retrieved 2 August 2023.
  10. ^ "Qaialdo". Union Register of medicinal products. 31 May 2023. Archived from the original on 6 June 2023. Retrieved 6 June 2023.
  11. ^ a b c d e f g Cite error: The named reference pmid15947888 was invoked but never defined (see the help page).
  12. ^ a b c d Maron BA, Leopold JA (September 2008). "Mineralocorticoid receptor antagonists and endothelial function". Current Opinion in Investigational Drugs. 9 (9): 963–9. PMC 2967484. PMID 18729003.
  13. ^ Carone L, Oxberry SG, Twycross R, Charlesworth S, Mihalyo M, Wilcock A (February 2017). "Spironolactone". Journal of Pain and Symptom Management. 53 (2): 288–292. doi:10.1016/j.jpainsymman.2016.12.320. PMID 28024992.
  14. ^ a b Cite error: The named reference TakamuraMaruyama1997 was invoked but never defined (see the help page).
  15. ^ Cite error: The named reference SzaszBudvari-Barany1990 was invoked but never defined (see the help page).
  16. ^ McDonagh TA, Gardner RS, Clark AL, Dargie H (14 July 2011). Oxford Textbook of Heart Failure. OUP Oxford. pp. 403–. ISBN 978-0-19-957772-9. Archived from the original on 27 March 2017.
  17. ^ Cite error: The named reference Parkinson2001 was invoked but never defined (see the help page).
  18. ^ Cite error: The named reference Klaassen2007 was invoked but never defined (see the help page).
  19. ^ Cite error: The named reference pmid7895608 was invoked but never defined (see the help page).
  20. ^ Cite error: The named reference BlackElliott2006 was invoked but never defined (see the help page).
  21. ^ Cite error: The named reference pmid14579013 was invoked but never defined (see the help page).
  22. ^ Friedman AJ (October 2015). "Spironolactone for Adult Female Acne". Cutis. 96 (4): 216–7. PMID 27141564.
  23. ^ Maizes V (2015). Integrative Women's Health (2 ed.). Oxford University Press. p. 746. ISBN 978-0-19-021480-7.
  24. ^ a b Burinkul S, Panyakhamlerd K, Suwan A, Tuntiviriyapun P, Wainipitapong S (July 2021). "Anti-Androgenic Effects Comparison Between Cyproterone Acetate and Spironolactone in Transgender Women: A Randomized Controlled Trial". The Journal of Sexual Medicine. 18 (7): 1299–1307. doi:10.1016/j.jsxm.2021.05.003. PMID 34274044.
  25. ^ a b Sehgal I (2023). "Review of adult gender transition medications: mechanisms, efficacy measures, and pharmacogenomic considerations". Frontiers in Endocrinology. 14: 1184024. doi:10.3389/fendo.2023.1184024. PMC 10355117. PMID 37476490.
  26. ^ Cosgrove B (January 2018). "The Case Against Spironolactone". Modern Trans Hormones. Retrieved 8 July 2024.
  27. ^ Deedwania PC (30 January 2014). Drug & Device Selection in Heart Failure. JP Medical Ltd. pp. 47–. ISBN 978-93-5090-723-8. Archived from the original on 7 October 2022. Retrieved 5 July 2017.
  28. ^ Ottow E, Weinmann H (9 July 2008). Nuclear Receptors As Drug Targets. John Wiley & Sons. p. 410. ISBN 978-3-527-62330-3. Archived from the original on 21 June 2013. Retrieved 28 May 2012.
  29. ^ Wermuth CG (24 July 2008). The Practice of Medicinal Chemistry. Academic Press. p. 34. ISBN 978-0-12-374194-3. Archived from the original on 21 June 2013. Retrieved 27 May 2012.
  30. ^ Sittig M (1988). Pharmaceutical Manufacturing Encyclopedia. William Andrew. p. 1385. ISBN 978-0-8155-1144-1. Archived from the original on 20 June 2013. Retrieved 27 May 2012.
  31. ^ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
  32. ^ "The Top 300 of 2022". ClinCalc. Archived from the original on 30 August 2024. Retrieved 30 August 2024.
  33. ^ "Spironolactone Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
  34. ^ Prior JC, Vigna YM, Watson D (1989). "Spironolactone with Physiological Female Steroids for Presurgical Therapy of Male-To-Female Transsexualism". Archives of Sexual Behavior. 18 (1): 49–57. doi:10.1007/BF01579291. PMID 2540730.