Brand names: Aldactone, CaroSpir
Drug class: Steroidal Mineralocorticoid Receptor Antagonists
VA class: CV704
CAS number: 52-01-7

Spironolactone is also contained as an ingredient in the following combinations:
Spironolactone and Hydrochlorothiazide

Medically reviewed by Drugs.com on Nov 21, 2023. Written by ASHP.

Introduction

Aldosterone antagonist; a potassium-sparing diuretic.

Uses for Spironolactone

Edema

Management of edema associated with excessive aldosterone, including in patients with cirrhosis of the liver, heart failure, and nephrotic syndrome.

Used as an adjunct to thiazide therapy when diuresis is inadequate or reduction of potassium excretion is necessary.

Hypertension

Management of hypertension usually in conjunction with other classes of antihypertensive agents; has been used for patients who cannot be treated adequately with other agents or for whom other agents are considered inappropriate.

Not considered a preferred agent for initial management of hypertension according to current evidence-based hypertension guidelines, but may be used as add-on therapy if BP not adequately controlled with the recommended antihypertensive drug classes (i.e., ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, thiazide diuretics); considered preferred add-on therapy by some experts for resistant hypertension and for hypertension associated with primary aldosteronism.

Some experts state that spironolactone may be useful for the management of resistant hypertension in patients with type 2 diabetes mellitus when added to an existing treatment regimen consisting of a renin-angiotensin system inhibitor (e.g., ACE inhibitor, angiotensin II receptor antagonist), diuretic, and calcium-channel blocker.

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension. (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP. However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) of <130/80 mm Hg in all adults, regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk. In addition, an SBP goal of <130 mm Hg generally is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg. These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.

Other hypertension guidelines generally based target BP goals on age and comorbidities. Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk, and have used higher BP thresholds and target BPs in elderly patients compared with those recommended by the 2017 ACC/AHA hypertension guideline.

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the 2017 ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient's BP treatment goal.

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors. ASCVD risk assessment is recommended by ACC/AHA for all adults with hypertension.

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg. Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP. Consider initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes in patients with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.

Heart Failure

Management of severe heart failure (NYHA class III-IV) in conjunction with standard therapy, to increase survival and reduce heart failure-related hospitalization.

Management of edema and sodium retention in heart failure in patients only partially responsive to, or intolerant of, other therapeutic measures.

ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend the addition of an aldosterone antagonist (i.e., spironolactone or eplerenone) in selected patients with heart failure and reduced LVEF who are already receiving an agent to inhibit the renin-angiotensin-aldosterone (RAA) system (e.g., ACE inhibitor, angiotensin II receptor antagonist, angiotensin receptor-neprilysin inhibitor [ARNI]) and a β-blocker; careful patient selection required to minimize the risk of hyperkalemia and renal insufficiency.

Aldosterone receptor antagonists also have been used to reduce morbidity and mortality following an acute MI in patients with reduced LVEF who develop symptoms of heart failure or have a history of diabetes mellitus^{† [off-label]}.

Primary Hyperaldosteronism

Short-term preoperative treatment of primary hyperaldosteronism.

Long-term maintenance therapy in patients with discrete aldosterone-producing adrenal adenomas who are not candidates for surgery (e.g., adrenalectomy).

Long-term maintenance therapy for patients with bilateral micronodular or macronodular adrenal hyperplasia (idiopathic hyperaldosteronism).

Precocious Puberty

Management of certain forms of gonadotropin releasing hormone (GnRH)-independent (peripheral) precocious puberty^{† [off-label]} (e.g., familial male precocious puberty [testotoxicosis]).

Hirsutism

Treatment of hirsutism^{† [off-label]} in women with polycystic ovary syndrome or idiopathic hirsutism.

Spironolactone Dosage and Administration

General

Monitoring and BP Treatment Goals

• Monitor BP regularly (i.e., monthly) during therapy and adjust dosage of the antihypertensive drug until BP controlled.

• If unacceptable adverse effects occur, discontinue drug and initiate another antihypertensive agent from a different pharmacologic class.

• Assess patient's renal function and electrolytes 2–4 weeks after initiation of diuretic therapy.

• If adequate BP response not achieved, either increase dosage of the drug or add another drug with demonstrated benefit and preferably a complementary mechanism of action (e.g., ACE inhibitor, angiotensin II receptor antagonist, calcium-channel blocker, thiazide diuretic). Many patients will require ≥2 drugs from different pharmacologic classes to achieve BP goal.

Administration

Administer orally.

Oral Administration

Administer tablets in single or divided doses.

An oral suspension (CaroSpir) currently is commercially available; however, it is not therapeutically equivalentto spironolactone tablets (e.g., Aldactone). The manufacturer of CaroSpir states that for spironolactone doses >100 mg, tablets should be used instead of the suspension because such doses of the oral suspension may result in higher than expected serum spironolactone concentrations. Administer oral suspension in single or divided doses.

For administration in children^{† [off-label]}, tablets may be pulverized and administered as an oral suspension in cherry syrup.

Dosage

Pediatric Patients

Edema† [off-label]

Tablets

Oral

3.3 mg/kg (up to 100 mg) daily as a single dose or in divided doses.

Alternatively, initial dosage of 60 mg/m² daily in divided doses.

Hypertension†

Tablets

Oral

Some experts have recommended an initial dosage of 1 mg/kg daily as a single dose or in 2 divided doses. Increase dosage as necessary up to a maximum of 3.3 mg/kg (up to 100 mg) daily as a single dose or in 2 divided doses.

Adults

Edema

Tablets

Oral

Initially, 100 mg daily in single or divided doses. Range: 25–200 mg daily.

As monotherapy, administer usual initial dosage for ≥5 days; if response is satisfactory, titrate to optimal dosage.

If response is not satisfactory after initial 5 days of therapy, add a thiazide or loop diuretic. Do not adjust spironolactone dosage during combined diuretic therapy.

Oral Suspension (CaroSpir)

Oral

Initially, 75 mg daily in a single dose or divided doses for treatment of edema associated with hepatic cirrhosis. Initiate therapy in a hospital setting and titrate slowly. Administer for ≥5 days before increasing dose to obtain desired effect when given as sole diuretic agent.

Spironolactone/Hydrochlorothiazide Fixed-combination Therapy

Oral

Spironolactone 100 mg daily and hydrochlorothiazide 100 mg daily as a single dose or in divided doses. Manufacturer states that optimal dosage should be established by individual titration of the drug components. Range: spironolactone 25–200 mg daily and hydrochlorothiazide 25–200 mg daily as a single dose or in divided doses. May be beneficial to administer separate tablets of either spironolactone or hydrochlorothiazide in addition to the fixed-combination of spironolactone and hydrochlorothiazide in order to provide optimal individual therapy in some instances.

Hypertension

Tablets

Oral

Usual initial dosage recommended by manufacturer: 25–100 mg daily as a single dose or in divided doses. Dosage may be titrated at 2-week intervals. Dosages >100 mg daily generally do not provide additional reductions in BP.

Some experts state that the usual dosage range is 25–100 mg once daily.

Oral Suspension (CaroSpir)

Oral

Initially, 20–75 mg daily in a single dose or divided doses; may titrate dosage at 2-week intervals. Dosages >75 mg daily generally do not provide additional reductions in blood pressure.

Spironolactone/Hydrochlorothiazide Fixed-combination Therapy

Oral

Spironolactone 50–100 mg daily and hydrochlorothiazide 50–100 mg daily as a single dose or in divided doses.

Manufacturer states that optimal dosage should be established by individual titration of the drug components. Dosage will vary depending on the results of titration.

Heart Failure

Tablets

Oral

Initially, 25 mg once daily recommended by manufacturer in patients with serum potassium concentration ≤5 mEq/L and eGFR >50 mL/minute per 1.73 m². If tolerated, may increase dosage to 50 mg once daily as clinically indicated. If 25-mg daily dosage not tolerated (i.e., hyperkalemia develops), may decrease dosage to 25 mg every other day.

Alternatively, ACCF/AHA recommend 12.5–25 mg once daily initially in patients with serum potassium concentration ≤5 mEq/L and eGFR ≥50 mL/minute per 1.73 m². May increase dosage to 25 mg once or twice daily after 4 weeks if clinically indicated and if serum potassium concentration ≤5 mEq/L and eGFR ≥50 mL/minute per 1.73 m².

Monitor closely for hyperkalemia and renal insufficiency. (See Hyperkalemia under Cautions.)

For management of fluid retention (e.g., edema) associated with heart failure, some experts recommend initiating spironolactone at a low dosage (e.g., 12.5–25 mg once daily) and increasing dosage until urine output increases and weight decreases, generally by 0.5–1 kg daily.

ACCF/AHA recommend holding spironolactone therapy if serum potassium >5.5 mEq/L or renal function worsens; consider resuming therapy at reduced dosage following resolution (for ≥72 hours) of hyperkalemia (serum potassium <5 mEq/L) and renal insufficiency.

Instruct patients to stop therapy with an aldosterone receptor antagonist if they have diarrhea or are dehydrated or if therapy with a concomitant loop diuretic is interrupted.

Oral Suspension (CaroSpir)

Oral

Initially, 20 mg once daily recommended by manufacturer in patients with serum potassium concentration ≤5 mEq/L and eGFR >50 mL/minute per 1.73 m². If tolerated, may increase dosage to 37.5 mg once daily as clinically indicated. If 20-mg daily dosage results in hyperkalemia, may decrease dosage to 20 mg every other day.

Primary Hyperaldosteronism

Medical Therapy Prior to Adrenalectomy

Oral

Tablets: Patients with a definitive diagnosis: 100–400 mg daily before surgery.

Treatment of Primary Hyperaldosteronism

Oral

Tablets: Use lowest effective dosage for long-term maintenance therapy in patients considered unsuitable for surgery.

Hirsutism†

Oral

Tablets: 50–200 mg daily. Regression of hirsutism evident within 2 months, maximal within 6 months, and has been maintained for ≥16 months with continued therapy.

Prescribing Limits

Pediatric Patients

Hypertension†

Oral

Tablets: Maximum 3.3 mg/kg (up to 100 mg) daily.

Adults

Edema

Oral

Tablets: Management of fluid retention in heart failure: ACCF/AHA recommends maximum 50 mg daily; higher dosage may be used with close monitoring.

Heart Failure

Oral

Tablets: ACCF/AHA recommends maximum 50 mg daily.

Special Populations

Hepatic Impairment

Patients with cirrhosis: Use lowest initial dose and titrate slowly; initiate therapy in the hospital.

Renal Impairment

Heart failure patients with eGFR 30–50 mL/minute per 1.73 m² (tablets): Initially, 25 mg every other day recommended by manufacturer. Alternatively, in patients with an eGFR of 30–49 mL/minute per 1.73 m², initial dosage of 12.5 mg once daily or every other day recommended by ACCF/AHA; maintenance dosage of 12.5–25 mg once daily (after 4 weeks of therapy and if serum potassium is ≤5 mEq/L).

Heart failure patients with eGFR 30–50 mL/minute per 1.73 m² (oral suspension [CaroSpir]): Initially, 10 mg once daily.

Heart failure patients with eGFR <30 mL/minute per 1.73 m²: ACCF/AHA states that use may be harmful because of potentially life-threatening hyperkalemia or renal insufficiency.

Cautions for Spironolactone

Contraindications

• Hyperkalemia.

• Addison's disease.

• Concomitant use of eplerenone.

Warnings/Precautions

Warnings

Hyperkalemia

Concomitant use of potassium supplements generally not recommended. Risk of hyperkalemia increased by impaired renal function or concomitant potassium supplementation, potassium-containing salt substitutes or drugs that increase potassium (e.g., ACE inhibitors, angiotensin II receptor antagonists). (See Specific Drugs, Foods, and Laboratory Tests under Interactions.)

Manufacturer recommends monitoring serum potassium within 1 week of initiating or titrating spironolactone therapy and regularly thereafter. Check serum potassium concentrations when dosages of concomitant ACE inhibitors or angiotensin II receptor antagonists are altered. ACCF/AHA recommend checking serum potassium and renal function within 2–3 days and again 7 days after initiation of an aldosterone antagonist; perform subsequent monitoring as needed based upon the stability of renal function and fluid status, but monitor at least monthly for the first 3 months and every 3 months thereafter.

If hyperkalemia occurs, decrease the dosage of spironolactone or discontinue the drug; hyperkalemia should be treated appropriately.

Electrolyte and Metabolic Abnormalities

In addition to hyperkalemia, spironolactone may cause hyponatremia, hypomagnesemia, hypocalcemia, hypochloremic alkalosis, and hyperglycemia. Asymptomatic hyperuricemia may occur and gout is rarely precipitated. Monitor serum electrolytes, uric acid, and blood glucose concentrations periodically in patients receiving spironolactone.

Sudden alterations of fluid and electrolyte balance may precipitate impaired neurologic function, worsening hepatic encephalopathy, and coma in patients with hepatic disease with cirrhosis and ascites. (See Hepatic Impairment under Cautions.)

Concomitant ACE Inhibitor Therapy

Combined therapy with spironolactone and an ACE inhibitor has been considered relatively contraindicated because of the potential for developing severe hyperkalemia and inhibition of aldosterone formation; however, clinical studies in patients with moderate or severe heart failure indicate addition of low-dose (25–50 mg daily) spironolactone to standard therapy (e.g., an ACE inhibitor and a loop diuretic with or without a cardiac glycoside) decreases mortality and hospitalization.

Renal Effects and Hypotension

Excessive diuresis may cause symptomatic dehydration, hypotension, and worsening renal function, especially in patients who are salt-depleted or those taking an ACE inhibitor or angiotensin II receptor antagonist. Worsening of renal function also may occur when spironolactone is used in conjunction with nephrotoxic drugs (e.g., aminoglycosides, cisplatin, NSAIAs). Monitor the patient's volume status and renal function periodically while receiving spironolactone therapy.

Gynecomastia

Gynecomastia reported; appears related to dosage and duration of therapy. Risk of gynecomastia may be higher than with eplerenone. Generally reversible upon discontinuance.

Use of Fixed Combinations

When spironolactone is used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.

Sensitivity Reactions

Anaphylaxis

Anaphylaxis reported.

Specific Populations

Pregnancy

Use of spironolactone during pregnancy may affect the sex differentiation of a male fetus during embryogenesis. Avoid spironolactone use during pregnancy because of the potential risk to the male fetus due to the antiandrogenic properties of the drug; advise pregnant women who receive spironolactone of the potential risk to a male fetus.

Lactation

Active metabolite canrenone distributed into milk. Consider developmental and health benefits of breastfeeding along with the mother's clinical need for spironolactone and any potential adverse effects on the breastfed child from spironolactone or from the underlying maternal condition.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

Monitor renal function.

Hepatic Impairment

Use with caution in patients with impaired hepatic function; sudden alterations of fluid and electrolyte balance may precipitate impaired neurologic function, worsening hepatic encephalopathy, and coma in patients with hepatic disease and cirrhosis and ascites. Initiate spironolactone therapy in the hospital in such patients.

Renal Impairment

Risk of adverse reactions may be greater in patients with impaired renal function. Patients with renal impairment are at increased risk of hyperkalemia; monitor potassium closely. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Most common adverse effect (incidence >5%): Gynecomastia.

Other adverse effects: Hyperkalemia; hypotension; worsening renal function; hyponatremia; hypomagnesemia; hypocalcemia; hypochloremic alkalosis; hyperglycemia; impaired neurologic function/coma in patients with hepatic impairment, cirrhosis and ascites.

Drug Interactions

Specific Drugs, Foods, and Laboratory Tests

Spironolactone Pharmacokinetics

Absorption

Well absorbed following oral administration. Peak serum concentrations of spironolactone usually attained within 2.6 or 0.5–1.5 hours with oral tablets or oral suspension (CaroSpir), respectively; peak serum concentrations of the principal metabolites (e.g., canrenone) usually attained within 4.3 hours (tablets) or 2.5–5 hours (oral suspension [CaroSpir]). Serum concentrations of spironolactone 15–37% higher following oral suspension (CaroSpir) than with oral tablets (Aldactone).

Bioavailability

>90%.

Onset

Gradual; maximum diuretic effect reached on third day.

Spironolactone in fixed combination with hydrochlorothiazide: Diuresis usually occurs on the first day.

Duration

Diuresis persists for 2–3 days after discontinuance.

Food

Food increases peak serum concentrations and AUC.

Distribution

Extent

Spironolactone and its metabolites crosses the placenta.

Canrenone, a major active metabolite, is distributed into milk.

Plasma Protein Binding

Spironolactone and canrenone: >90%.

Elimination

Metabolism

Rapidly and extensively metabolized; canrenone and/or 7α-thiomethylspironolactone appear to be major active metabolites.

Undergoes hepatic deacetylation, thiomethylation, and hydroxylation.

Elimination Route

Excreted principally in urine as metabolites and to a lesser extent in bile.

Half-life

Spironolactone: 1–2 hours.

Metabolites: 10–35 hours depending on formulation.

Stability

Storage

Oral

Tablets

<25°C.

Suspension

CaroSpir: 20–25°C (may be exposed to 15–30°C)

Extemporaneously prepared oral suspensions in cherry syrup: Reported to be stable for 1 month at 2–8°C.

Actions

• Synthetic steroid mineralocorticoid receptor antagonist (aldosterone antagonist).

• Exhibits magnesium- and potassium-sparing, natriuretic, diuretic, and hypotensive effects by competitively inhibiting the physiologic effects of the adrenocortical hormone aldosterone on the distal renal tubules, myocardium, and vasculature.

• Androgen and progesterone receptor antagonist.

Advice to Patients

• Importance of advising patients to take the drug consistently with respect to food.

• Importance of advising patient to avoid ingestion of potassium supplements, potassium-rich foods, or salt substitutes.

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed. Advise a pregnant woman of the potential risk to a male fetus.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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Frequently asked questions

• What is the strength of CaroSpir (spironolactone) oral suspension?

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