spironolactone (Aldactone)
Jump to navigation
Jump to search
Introduction
Tradename: Aldactone.
Indications
- treatment of hypertension
- treatment of edema
- treatment of ascites & edema associated with alcoholic liver disease
- treatment of hyperaldosteronism
- short-term preoperative treatment of hyperaldosteronism
- long-term treatment of primary hyperaldosteronism with bilateral adrenal hyperplasia
- long-term maintenance therapy in patients with aldosterone-producing adrenal adenomas
- treatment of hypokalemia when other treatment is inappropriate or indadequate
- used in combination with testosterone in the management of certain forms of gonadotropin-releasing hormone- independent precocious puberty
- congestive heart failure due to LV systolic dysfunction
- LV diastolic dysfunction (probably not)
- improves diastolic function
- not associated with clinical improvement[16][17]
- associated with marginally significant reduction in hospitalizations for heart failure[14][17] 9 treatment of polycystic ovary syndrome[9]
- chronic renal disease due to diabetic nephropathy[12]
- does not slow the progression of kidney disease independent of blood pressure control[18]*
- adjunct to loop diuretic in nephrotic syndrome
- treatment of acne[19][21]
* ref[18] makes no mention of ref[12]
Contraindications
- renal insufficiency:
- hypersensitivity to spironolactone
- hyperkalemia (serum K+ > 5 meq/L)
- concurrent use of other K+ sparing diuretics
- concurrent use of K+ supplements
Dosage
- edema:
- hypertension
- ascites:
- congestive heart failure:
- diagnosis of primary hyperaldosteronism:
- 100 to 400 mg/day in 1-2 divided doses
Tabs: 25, 50, 100 mg.
Pharmacokinetics
- oral bioavailability is about 90%
- onset of action (gradual)
- extensive hepatic metabolism to active metabolites that are eliminated in the urine
- duration of action: 2-3 days (multiple doses)
- elimination 1/2life
- 1.4 hours for spironolactone
- 13.8 & 16.5 hours for active metabolites[4]
elimination via liver
elimination via kidney
Monitor
- serum K+[7][13]
- reinitiate serum K+ monitoring cycle if ACE inhibitor or ARB added or their dose increased[13]
- serum creatinine levels may be increased by spironolactone by 20%; discontinue spironlactone when estimated GFR < 30 mL/min[14]
Adverse effects
- not common (1-10%)
- uncommon (< 1%)
- other
- does not increase risk of breast cancer[15]
- not associated with a increased risk of cancer[20]
- associated with a decreased risk of prostate cancer[20]
* hyperkalemia:
- 50 hospitalizations per 1000 new prescriptions[10]
- 11 hospitalizations per 1000 new prescriptions[11]
- mortality associated with hospitalization NOT insignificant
- drug adverse effects of renin-angiotensin-aldosterone system inhibitors (RAAS inhibitors)
- drug adverse effects of diuretics
- drug adverse effects of antihypertensive agents
Drug interactions
- NSAIDs in combination potentiate hyperkalemia & antagonize diuretic effect
- ACE inhibitors in combination potentiate hyperkalemia
- digoxin in combination increases incidence of gynecomastia
- other K+ sparing diuretics in combination potentiate hyperkalemia
- 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 trimethoprim
- 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 spironolactone with ACE inhibitors
- drug interaction(s) of diuretics with angiotensin II receptor antagonists
- drug interaction(s) of diuretics with ACE inhibitors
- drug interaction(s) of spironolactone with beta blockers
- 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
Test interactions
- spironolactone interferes with plasma aldosterone/renin ratio
Mechanism of action
- an aldosterone antagonist & an androgen antagonist
- K+ sparing diuretic
- inhibits action of aldosterone at the distal tubule & collecting duct
- causes excretion of Na+, Cl- & H2O
- decreases excretion of K+, NH4+, titratable acid & phosphate
- since most Na+ is eliminated in the proximal tubule, spironolactone has minimal effects when used alone; combination with a thiazide or loop diuretic is necessary for maximum effect
More general terms
Additional terms
Component of
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 620
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 473-74
- ↑ 4.0 4.1 Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ a: Journal Watch, Mass Med Soc 20(1):7 (Jan 1) 2000 b: N Engl J Med 341:709, 1999
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ 7.0 7.1 7.2 Prescriber's Letter 10(3):15 2003
- ↑ 8.0 8.1 Prescriber's Letter 11(1):1 2004 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=200115&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 9.0 9.1 Journal Watch 24(14):115, 2004 Ganie MA, Khurana ML, Eunice M, Gulati M, Dwivedi SN, Ammini AC. Comparison of efficacy of spironolactone with metformin in the management of polycystic ovary syndrome: an open-labeled study. J Clin Endocrinol Metab. 2004 Jun;89(6):2756-62. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15181054
- ↑ 10.0 10.1 Prescriber's Letter 11(9): 2004 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=200905&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 11.0 11.1 Journal Watch 24(17):133, 2004 Juurlink DN, Mamdani MM, Lee DS, Kopp A, Austin PC, Laupacis A, Redelmeier DA. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med. 2004 Aug 5;351(6):543-51. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15295047
- ↑ 12.0 12.1 12.2 Rossing K et al. Beneficial effects of adding spironolactone to recommended antihypertensive treatment in diabetic nephropathy. A randomized, double-masked, cross-over study. Diabetes Care 2005 Sep; 28:2106-12. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16123474
- ↑ 13.0 13.1 13.2 13.3 13.4 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
- ↑ 14.0 14.1 14.2 14.3 Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010
Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022 - ↑ 15.0 15.1 Mackenzie IS et al. Spironolactone and risk of incident breast cancer in women older than 55 years: Retrospective, matched cohort study. BMJ 2012 Jul 13; 345:e4447 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22797844
- ↑ 16.0 16.1 Edelmann F et al Effect of Spironolactone on Diastolic Function and Exercise Capacity in Patients With Heart Failure With Preserved Ejection Fraction. The Aldo-DHF Randomized Controlled Trial. JAMA. 2013;309(8):781-791 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23443441 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1656252
Cleland JGF and Pellicori P Defining Diastolic Heart Failure and Identifying Effective Therapies. JAMA. 2013;309(8):825-826. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23443447 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1656233 - ↑ 17.0 17.1 17.2 Pitt B, Pfieffer MA, Assmann SF et al Spironolactone for Heart Failure with Preserved Ejection Fraction. N Engl J Med 2014; 370:1383-1392. April 10, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24716680 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1313731
Ferreira JP, Rossello X, Pocock SJ et al. Spironolactone dose in heart failure with preserved ejection fraction: findings from TOPCAT. Eur J Heart Fail. 2020;22(9):1615-1624 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32452128 https://onlinelibrary.wiley.com/doi/10.1002/ejhf.1909
Kalogeropoulos AP, Thankachen J, Butler J et al. Diuretic and renal effects of spironolactone and heart failure hospitalizations: a TOPCAT Americas analysis. Eur J Heart Fail. 2020;22(9):1600-1610 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32469156 https://onlinelibrary.wiley.com/doi/10.1002/ejhf.191 - ↑ 18.0 18.1 18.2 NEJM. Knowledge+. Oct 14, 2014 http://knowledgeplus.nejm.org/question-of-week/1161/
- ↑ 19.0 19.1 19.2 Plovanich M et al Low Usefulness of Potassium Monitoring Among Healthy Young Women Taking Spironolactone for Acne. JAMA Dermatol. Published online March 22, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25796182 <Internet> http://archderm.jamanetwork.com/article.aspx?articleid=2194951
Graber EM K+larity for Spironolactone At Last! JAMA Dermatol. Published online March 22, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25796224 <Internet> http://archderm.jamanetwork.com/article.aspx?articleid=2194950 - ↑ 20.0 20.1 20.2 Bommareddy K, Hamade H, Lopez-Olivo MA et al Association of Spironolactone Use With Risk of Cancer. A Systematic Review and Meta-analysis. JAMA Dermatol. 2022;158(3):275-282. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35138351 PMCID: PMC8829743 Free PMC article https://jamanetwork.com/journals/jamadermatology/fullarticle/2788624
- ↑ 21.0 21.1 Santer M et al. Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: Pragmatic, multicentre, phase 3, double blind, randomised controlled trial. BMJ 2023 May 16; 381:e074349. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37192767 Free article https://www.bmj.com/content/381/bmj-2022-074349