Home > Medical Reference > Complementary Medicine

Spironolactone


Pronunciation

 (speer on oh LAK tone)


U.S. Brand Names

 Aldactone®


Generic Available

 Yes


Canadian Brand Names

 Aldactone®; Novo-Spiroton


Use

 Management of edema associated with excessive aldosterone excretion; hypertension; primary hyperaldosteronism; hypokalemia; treatment of hirsutism; cirrhosis of liver accompanied by edema or ascites


Use - Unlabeled/Investigational

 Female acne (adjunctive therapy); hirsutism; hypertension (pediatric); diuretic (pediatric)


Pregnancy Risk Factor

 C/D in pregnancy-induced hypertension (per expert analysis)


Pregnancy Implications

 Teratogenic effects were not observed in animal studies; however, doses used were less than or equal to equivalent doses in humans. The antiandrogen effects of spironolactone have been shown to cause feminization of the male fetus in animal studies. Two case reports did not demonstrate this effect in humans however, the authors caution that adequate data is lacking. Diuretics are generally avoided in pregnancy due to the theoretical risk that decreased plasma volume may cause placental insufficiency. Diuretics should not be used during pregnancy in the presence of reduced placental perfusion (eg, pre-eclampsia, intrauterine growth restriction).


Lactation

 Enters breast milk/not recommended (AAP rates "compatible")


Contraindications

 Hypersensitivity to spironolactone or any component of the formulation; anuria; acute renal insufficiency; significant impairment of renal excretory function; hyperkalemia; pregnancy (pregnancy-induced hypertension - per expert analysis)


Warnings/Precautions

 Avoid potassium supplements, potassium-containing salt substitutes, a diet rich in potassium, or other drugs that can cause hyperkalemia. Monitor for fluid and electrolyte imbalances. Gynecomastia is related to dose and duration of therapy. Diuretic therapy should be carefully used in severe hepatic dysfunction; electrolyte and fluid shifts can cause or exacerbate encephalopathy. Discontinue use prior to adrenal vein catheterization.


Adverse Reactions

 Incidence of adverse events is not always reported. (Mean daily dose: 26 mg)

Cardiovascular: Edema (2%, placebo 2%)

Central nervous system: Disorders (23%, placebo 21%) which may include drowsiness, lethargy, headache, mental confusion, drug fever, ataxia, fatigue

Dermatologic: Maculopapular, erythematous cutaneous eruptions, urticaria, hirsutism, eosinophilia

Endocrine & metabolic: Gynecomastia (men 9%; placebo 1%), breast pain (men 2%; placebo 0.1%), serious hyperkalemia (2%, placebo 1%), hyponatremia, dehydration, hyperchloremic metabolic acidosis in decompensated hepatic cirrhosis, inability to achieve or maintain an erection, irregular menses, amenorrhea, postmenopausal bleeding

Gastrointestinal: Disorders (29%, placebo 29%) which may include anorexia, nausea, cramping, diarrhea, gastric bleeding, ulceration, gastritis, vomiting

Genitourinary: Disorders (12%, placebo 11%)

Hematologic: Agranulocytosis

Hepatic: Cholestatic/hepatocellular toxicity

Renal: Increased BUN concentration

Respiratory: Disorders (32%, placebo 34%)

Miscellaneous: Deepening of the voice, anaphylactic reaction, breast cancer


Overdosage/Toxicology

 Symptoms of overdose include drowsiness, confusion, clinical signs of dehydration and electrolyte imbalance, and hyperkalemia. Ingestion of large amounts of potassium-sparing diuretics may result in life-threatening hyperkalemia. This can be treated with I.V. glucose, with concurrent regular insulin. Sodium bicarbonate may also be used as a temporary measure. If needed, Kayexalate® oral or rectal solutions in sorbitol may also be used.


Drug Interactions

ACE inhibitors can cause hyperkalemia, especially in patients with renal impairment, potassium-rich diets, or on other drugs causing hyperkalemia; avoid concurrent use or monitor closely.

Cholestyramine can cause hyperchloremic acidosis in cirrhotic patients; avoid concurrent use.

Digoxin's positive inotropic effect may be reduced; serum levels of digoxin may increase.

Mitotane loses its effect; avoid concurrent use.

Potassium supplements may increase potassium retention and cause hyperkalemia; avoid concurrent use.

Salicylates and NSAIDs may interfere with the natriuretic action of spironolactone.


Ethanol/Nutrition/Herb Interactions

Food: Food increases absorption.

Herb/Nutraceutical: Avoid natural licorice (due to mineralocorticoid activity)


Stability

 Protect from light


Mechanism of Action

 Competes with aldosterone for receptor sites in the distal renal tubules, increasing sodium chloride and water excretion while conserving potassium and hydrogen ions; may block the effect of aldosterone on arteriolar smooth muscle as well


Pharmacodynamics/Kinetics

Protein binding: 91% to 98%

Metabolism: Hepatic to multiple metabolites, including canrenone (active)

Half-life elimination: 78-84 minutes

Time to peak, serum: 1-3 hours (primarily as the active metabolite)

Excretion: Urine and feces


Dosage

 To reduce delay in onset of effect, a loading dose of 2 or 3 times the daily dose may be administered on the first day of therapy. Oral:

Children:

Diuretic, hypertension (unlabeled use): Children 1-17 years: Initial: 1 mg/kg/day divided every 12-24 hours (maximum dose: 3.3 mg/kg/day, up to 100 mg/day)

Diagnosis of primary aldosteronism (unlabeled use): 125-375 mg/m 2 /day in divided doses

Adults:

Edema, hypokalemia: 25-200 mg/day in 1-2 divided doses

Hypertension (JNC 7): 25-50 mg/day in 1-2 divided doses

Diagnosis of primary aldosteronism: 100-400 mg/day in 1-2 divided doses

Acne in women (unlabeled use): 25-200 mg once daily

Hirsutism in women (unlabeled use): 50-200 mg/day in 1-2 divided doses

CHF, severe (with ACE inhibitor and a loop diuretic ± digoxin): 25 mg/day, increased or reduced depending on individual response and evidence of hyperkalemia

Elderly: Initial: 25-50 mg/day in 1-2 divided doses, increasing by 25-50 mg every 5 days as needed.

Dosing interval in renal impairment:

Clcr 10-50 mL/minute: Administer every 12-24 hours.

Clcr<10 mL/minute: Avoid use.


Monitoring Parameters

 Blood pressure, serum electrolytes (potassium, sodium), renal function, I & O ratios and daily weight throughout therapy


Test Interactions

 May cause false elevation in serum digoxin concentrations measured by RIA


Dietary Considerations

 Should be taken with food to decrease gastrointestinal irritation and to increase absorption. Excessive potassium intake (eg, salt substitutes, low-salt foods, bananas, nuts) should be avoided.


Patient Education

 Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Take as directed, with meals. Do not increase dietary potassium. Avoid natural licorice. Weigh yourself weekly at the same time, in the same clothes, and report weight loss >5 lb/week. May cause dizziness, drowsiness, confusion, or headache (use caution when driving or engaging in tasks requiring alertness until response to drug is known); nausea, vomiting, or dry mouth (small, frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help); or decreased sexual ability, gynecomastia, impotence, menstrual irregularities (reversible with discontinuing of medication). Report mental confusion; clumsiness; persistent fatigue, chills, numbness, or muscle weakness in hands, feet, or face; acute persistent diarrhea; breast tenderness or increased body hair in females; breast enlargement or inability to achieve erection in males; chest pain, rapid heartbeat, or palpitations; excessive thirst; or respiratory difficulty. Pregnancy precaution: Do not get pregnant while taking this medication. Consult prescriber for appropriate barrier contraceptive measures.


Additional Information

 Maximum diuretic effect may be delayed 2-3 days and maximum hypertensive effects may be delayed 2-3 weeks.


Anesthesia and Critical Care Concerns/Other Considerations

 In severe heart failure, spironolactone (25 mg/day), when combined with maximal standard therapy, resulted in a striking improvement in cardiovascular outcome ( N Engl J Med , 1999, 341:709-17).

Potassium levels should be monitored in patients on an aldosterone blocker, particularly in those who have underlying renal impairment or concurrent ACE inhibitor therapy.


Cardiovascular Considerations

 In severe heart failure, spironolactone (25 mg/day), when combined with maximal standard therapy, resulted in a striking improvement in cardiovascular outcome (Pitt B, 1999). The ACC/AHA Guidelines for chronic heart failure management suggests consideration of low dose spironolactone in patients with recent or recurrent symptoms at rest despite maximum medical management. Patients should have a serum potassium <5 mEq/L and a serum creatinine <2.5 mg/dL measured prior to initiation of therapy. The guidelines also suggest reducing or stopping potassium supplements with initiation of spironolactone. In the RALES trial potassium supplementation was stopped with the initiation of spironolactone unless the patient was hypokalemic. Recently, a group of investigators published an observational study evaluating the effect of the RALES study (Pitt B, 1999) on hospitalization for hyperkalemia in an older (>66 years of age) heart failure population on ACE inhibitors. This study was a population-based, timed-series analysis of health care databases in Ontario, Canada from January 1994 through December 2001. Computerized prescription records were reviewed to identify prescriptions for spironolactone, ACE inhibitors, angiotensin receptor antagonists, beta-blockers, loop diuretics, nonsteroidal anti-inflammatory agents, potassium supplements, thiazide diuretics or other potassium sparing diuretics. and hospitalization records were reviewed to identify hospitalizations for hyperkalemia or heart failure. Among patients treated with ACE inhibitors who had recently been hospitalized for heart failure, the spironolactone prescription rate significantly increased after RALES publication (34 per 1000 patients in 1994 and 149 per 1000 patients in 2001). The rate of hospitalizations for hyperkalemia significantly rose from 2.4 per 1000 patients (1994) to 11 per 1000 patients (2001). The associated mortality significantly rose from 0.2 per 1000 (1994) to 2 per 1000 (2001). The authors concluded that closer laboratory monitoring may be necessary, in addition to proper prescribing of spironolactone.

Some clinicians recommend monitoring serum potassium and creatinine concentrations at least every 2 weeks for at least 12 weeks, then every 3-6 months after that. In the RALES trial, laboratory parameters were evaluated every 4 weeks for a year, every 3 months for a year and then every 6 months. Palmer (Palmer BF, 2004) gives some tips for managing patients at risk of hyperkalemia caused by inhibitors of the Renin-Angiotensin-Aldosterone system. If serum potassium increases to a level of more that 5.4 mEq/L while on spironolactone, dose reduction is suggested. The RALES trial used 25 mg every other day as the lowest maintenance dose possible.

Hypertension: Aldosterone antagonists may add additional antihypertensive benefits in patients who have severe LV dysfunction (NYHA class III and IV), but only after ACE inhibitors and beta-blockers have been instituted (if no contraindications or intolerances exist).


Dental Health: Effects on Dental Treatment

 No significant effects or complications reported


Dental Health: Vasoconstrictor/Local Anesthetic Precautions

 No information available to require special precautions


Mental Health: Effects on Mental Status

 May cause drowsiness, dizziness, nervousness, or confusion


Mental Health: Effects on Psychiatric Treatment

 Has been used to treat lithium-related edema


Dosage Forms

 Tablet: 25 mg, 50 mg, 100 mg


Extemporaneously Prepared

 A 25 mg/mL oral suspension can be prepared by crushing one hundred twenty (120) 25 mg tablets in a mortar (reducing to a fine powder), and then mixing in 20 mL of vehicle (a 1:1 combination of Ora-Sweet® or Ora-Sweet® SF and Ora-Plus®) to create a uniform paste. Continue to add vehicle in geometric amounts (while mixing) until near-final volume is achieved. Transfer to a graduate and add sufficient quantity to make 120 mL. Label "shake well" and "refrigerate." Refrigerated stability is 60 days.

Allen LV Jr and Erickson MA III, "Stability of Ketoconazole, Metolazone, Metronidazole, Procainamide Hydrochloride, and Spironolactone in Extemporaneously Compounded Oral Liquids," Am J Health Syst Pharm , 1996, 53:2073-8.

Nahata MC, Morosco RS, and Hipple TF, 4th ed, Pediatric Drug Formulations , Cincinnati, OH: Harvey Whitney Books Co, 2000.


References

American Academy of Pediatrics Committee on Drugs, "The Transfer of Drugs and Other Chemicals Into Human Milk," Pediatrics , 2001, 108(3):776-89.

Barrilleaux PS and Martin Jr JN, "Hypertension Therapy During Pregnancy," Clin Obstet Gynecol , 2002, 45(1):22-34.

Bozkurt B, Agoston I, and Knowlton AA, "Complications of Inappropriate Use of Spironolactone in Heart Failure: When an Old Medicine Spirals Out of New Guidelines," J Am Coll Cardiol , 2003, 41(2):211-4.

Chobanian AV, Bakris GL, Black HR, et al, "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure," JAMA , 2003, 289(19):2560-71.

Groves TD and Corenblum B, "Spironolactone Therapy During Human Pregnancy," Am J Obstet Gynecol , 1995, 172(5):1655-6.

Hunt SA, Baker DW, Chin MH, et al, "ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure)," J Am Coll Cardiol , 2001, 38(7):2101-13

Hunter MH and Carek PJ, "Evaluation and Treatment of Women With Hirsutism," Am Fam Physician , 2003, 67(12):2565-72.

Juurlink DN, Mamdani MM, Lee DS, et al, "Rates of Hyperkalemia After Publication of the Randomized Aldactone Evaluation Study," N Engl J Med , 2004, 351(6):543-51.

"National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Pediatrics , 2004, 114(2 Suppl 4th Report):555-76.

Palmer BF, "Managing Hyperkalemia Caused by Inhibitors of the Rennin-Angiotensin-Aldosterone System," N Engl J Med , 2004, 351:585-92.

Pitt B, Zannad F, Remme WJ, et al, "The Effect of Spironolactone on Morbidity and Mortality in Patients With Severe Heart Failure. Randomized Aldactone Evaluation Study Investigators," N Engl J Med , 1999, 341(10):709-17.

Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy," Am J Obstet Gynecol , 2000, 183(1):S1-22.

Rigo J Jr, Glaz E, and Papp Z, "Low or High Doses of Spironolactone for Treatment of Maternal Bartter's Syndrome," Am J Obstet Gynecol , 1996, 174(1 Pt 1):297.

Shaw JC, " Acne: Effect of Hormones on Pathogenesis and Management. Am J Clin Dermatol , 2002, 3(8):571-8.

Thiboutot D and Chen W, "Update and Future of Hormonal Therapy in Acne," Dermatology , 2003, 206(1):57-67.


International Brand Names

 Aldactone-A® (AR, CR, ES, GT, HN, MX, PA, SV, TR); Aldactone® (AT, AU, BE, BR, CA, CH, CO, CY, CZ, DE, EG, ES, FI, FR, GB, HK, HR, ID, IE, IL, IN, IT, JO, KW, LB, LU, MT, MX, NL, NO, NZ, PT, RO, RU, SE, SG, SI, SY, TH, TR, ZA); Aldonar® (PT); Aldopur® (AT); Aldospirone® (IL); Altone® (TH); Aporasnon® (JP); Aquareduct® (DE); Carpiaton® (ID); Digi-Aldopur® (AT); duraspiron® (DE); Espironolactona Alter® (ES); Espironolactona® (CL); Espironolactona Denver® (AR); Espironolactona Farmabio® (ES); Espironolactona L.CH.® (CL); Espironolactona Mundogen® (ES); Flumach® (FR); Frumikal® (DE); Hexalacton® (DK); Huma-Spiroton® (HU); Hyles® (TH); Jenaspiron® (DE); Lacalmin® (JP); Lanx® (AR); Letonal® (ID); Nefrolactona® (PT); Nefrotone® (BE); Novo-Spiroton (CA); Osiren® (AR); Osyrol® [compr.] (DE); Pilactone® (BD); Polspiron® (PL); Pondactone® (TH); Practon® (FR); Priul® (HR); Rolab-Spironolactone® (ZA); Spiractin® (AU, ZA); Spiresis® (FI); Spirix® (DK, FI, NO, RU, SE); Spirobene® (AT); Spirobeta® (DE); Spiroctan® (FR, LU); spiro® (CZ); Spiroderm® (IT); Spirogamma® (DE); Spirohexal® (AT); Spirolacton® (ID); Spirolang® (IT); Spirolon® (CY, EC); Spirolone® (CZ, HU); Spiro L.U.T.® (DE); Spiron® (BD, DK, HU); Spironex® (TH); Spirono Genericon® (AT); Spirono-Isis® (DE); Spironolacton Agepha® (AT); Spironolacton AL® (DE); Spironolactona® (RO); Spironolacton® (BG, PL, YU); Spironolacton-Cophar® (CH); Spironolactone BC® (BE); Spironolactone® (BE, GB); Spironolactone EG® (BE); Spironolactone-Eurogenerics® (LU); Spironolactone-Searle® (LU); Spironolacton Heumann® (DE); Spironolacton Hexal® (DE); Spironolacton-ratiopharm® (DE, LU); Spironolacton Sandoz® (DE); Spironolacton Stada® (DE, PL); Spironolacton TAD® (DE); Spironolakton NM Pharma® (SE); Spironol® (IL, PL); Spironone® (FR); Spiroscand® (SE); Spirospare® (GB); Spirotone® (NZ); spiro von ct® (DE); Uractone® (CZ, LU, RU); Uractonum® (SG); Urusonin® (JP); Verospiron® (BD, CZ, DE, HU, PL, RO, RU); Xenalon® (CH)


A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is the first of its kind, requiring compliance with 53 standards of quality and accountability, verified by independent audit. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial process . A.D.A.M. is also a founding member of Hi-Ethics (www.hiethics.com) and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2007 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.
adam.com