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Spironolactone

Class: Mineralocorticoid (Aldosterone) Receptor Antagonists
VA Class: CV704
CAS Number: 52-01-7
Brands: Aldactone

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

Medically reviewed by Drugs.com. Last updated on May 6, 2019.

Warning

  • Tumorigenic in chronic toxicity studies in rats.256 265 Manufacturer recommends use for FDA-approved indications only; avoid unnecessary use.256 265

  • Spironolactone/hydrochlorothiazide fixed combination not indicated for initial therapy of edema or hypertension.256 Individualize dosage.256 If the fixed combination represents the dosage so determined, its use may be more convenient in patient management.256 The treatment of hypertension and edema is not static but must be reevaluated as conditions in each patient warrant.256 (See Dosage and Administration.)

Introduction

Aldosterone antagonist; a potassium-sparing diuretic.256 265

Uses for Spironolactone

Edema

Management of edema associated with excessive aldosterone, including in patients with cirrhosis of the liver, heart failure, and nephrotic syndrome.265

Used as an adjunct to thiazide therapy when diuresis is inadequate or reduction of potassium excretion is necessary.265

Hypertension

Management of hypertension alone or in combination with other classes of antihypertensive agents;256 265 1200 has been used for patients who cannot be treated adequately with other agents or for whom other agents are considered inappropriate.265

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.501 502 503 504 1200

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.1215

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).501 502 503 504 515 1200 1201

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension.1200 (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).

Table 1. ACC/AHA BP Classification in Adults1200

Category

SBP (mm Hg)

DBP (mm Hg)

Normal

<120

and

<80

Elevated

120–129

and

<80

Hypertension, Stage 1

130–139

or

80–89

Hypertension, Stage 2

≥140

or

≥90

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP.1200 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.501 503 504 505 506 507 508 515 523 526 530 1200 1201 1207 1209 1222 1223 1229

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.1200 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.1200 These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.1200 1202 1210

Other hypertension guidelines generally based target BP goals on age and comorbidities.501 504 536 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 patients501 504 536 compared with those recommended by the 2017 ACC/AHA hypertension guideline.1200

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.1222 1223 1224 1229

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.1200 1220 1229

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors.1200 1207 ASCVD risk assessment is recommended by ACC/AHA for all adults with hypertension.1200

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%).1200

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.1200

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.1200 Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.502 1200

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.1200 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.1200

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.265 524 700

Management of edema and sodium retention in heart failure in patients only partially responsive to, or intolerant of, other therapeutic measures.265

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.524 700

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.524

Primary Hyperaldosteronism

Diagnosis of primary hyperaldosteronism by therapeutic trial;265 test results may be equivocal and additional diagnostic studies often required.a

Short-term preoperative treatment of primary hyperaldosteronism.265

Long-term maintenance therapy in patients with discrete aldosterone-producing adrenal adenomas who cannot undergo adrenalectomy or who decline surgery.265

Long-term maintenance therapy for patients with bilateral micronodular or macronodular adrenal hyperplasia (idiopathic hyperaldosteronism).265

Hypokalemia

Treatment of hypokalemia when oral potassium supplements or other measures are inappropriate or inadequate.265

Prophylaxis of hypokalemia in patients taking digitalis when other measures are inappropriate or inadequate.265

Precocious Puberty

Management of certain forms of gonadotropin releasing hormone (GnRH)-independent (peripheral) precocious puberty (e.g., familial male precocious puberty [testotoxicosis]).203 204 205 206 207 208 211 213

Hirsutism

Treatment of hirsutism in women with polycystic ovary syndrome or idiopathic hirsutism.210

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.1200

  • If unacceptable adverse effects occur, discontinue drug and initiate another antihypertensive agent from a different pharmacologic class.1200 1216

  • Assess patient's renal function and electrolytes 2–4 weeks after initiation of diuretic therapy.1200

  • 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).1200 1216 Many patients will require ≥2 drugs from different pharmacologic classes to achieve BP goal.1200 1216 1220

Administration

Administer orally.256 265

Oral Administration

Administer tablets in single or divided doses; 2 doses daily may be adequate.265

An oral suspension (CaroSpir) currently is commercially available; however, it is not therapeutically equivalent to spironolactone tablets (e.g., Aldactone).300 The manufacturer of CaroSpir states that tablets should be used for doses >100 mg because such doses of the oral suspension may result in higher than expected serum spironolactone concentrations.300 Administer oral suspension in single or divided doses.300

For administration in children, tablets may be pulverized and administered as an oral suspension in cherry syrup.a

When used with a thiazide diuretic in edema associated with cirrhosis of the liver, administer spironolactone for 2–3 days prior to the thiazide diuretic in order to prevent potassium depletion and precipitation of hepatic coma.a

Dosage

Pediatric Patients

Edema
Tablets
Oral

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

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

Hypertension
Tablets
Oral

Some experts have recommended an initial dosage of 1 mg/kg daily as a single dose or in 2 divided doses.269 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.269

Primary Hyperaldosteronism
Diagnosis
Oral

Tablets: 125–375 mg/m2 in divided doses over 24 hours.a

If serum potassium concentration increases during therapy but decreases when the drug is discontinued, a presumptive diagnosis of primary hyperaldosteronism should be considered.265

Adults

Edema
Tablets
Oral

Initially, 100 mg daily in single or divided doses.265 Range: 25–200 mg daily.265

As monotherapy, administer usual initial dosage for ≥5 days; if response is satisfactory, titrate to optimal dosage.265

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.524

If response is not satisfactory after initial 5 days of therapy, add a thiazide or loop diuretic.265 Do not adjust spironolactone dosage during combined diuretic therapy.265

Oral Suspension (CaroSpir)
Oral

Initially, 75 mg daily in a single dose or divided doses for treatment of edema associated with hepatic cirrhosis.300 Initiate therapy in a hospital setting and titrate slowly.300 Administer for ≥5 days before increasing dose to obtain desired effect when given as sole diuretic agent.300

Spironolactone/Hydrochlorothiazide Fixed-combination Therapy
Oral

Spironolactone 100 mg daily and hydrochlorothiazide 100 mg daily as a single dose or in divided doses.256 Range: spironolactone 25–200 mg daily and hydrochlorothiazide 25–200 mg daily as a single dose or in divided doses.256

Initial use of fixed-combination preparations is not recommended; adjust by administering each drug separately, then use the fixed combination if the optimum maintenance dosage corresponds to the ratio of drugs in the combination preparation.256 Administer separately for subsequent dosage adjustment.256

Hypertension
Tablets
Oral

Usual initial dosage recommended by manufacturer: 50–100 mg daily as a single dose or in divided doses.265 Full hypotensive response may require 2 weeks.265

Some experts state that the usual dosage range is 25–100 mg once daily.1200

Oral Suspension (CaroSpir)
Oral

Initially, 20–75 mg daily in a single dose or divided doses; may titrate dosage at 2-week intervals.300 Dosages >75 mg daily generally do not provide additional reductions in blood pressure.300

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.256

Initial use of fixed-combination spironolactone/hydrochlorothiazide preparations is not recommended; adjust by administering each drug separately, then use the fixed combination if the optimum maintenance dosage corresponds to the ratio of drugs in the combination preparation.256 Administer separately for subsequent dosage adjustment.256

Heart Failure
Tablets
Oral

Initially, 25 mg once daily recommended by manufacturer in patients with serum potassium concentration ≤5 mEq/L and Scr ≤2.5 mg/dL.265 If tolerated, may increase dosage to 50 mg once daily as clinically indicated.265 If 25-mg daily dosage not tolerated, may decrease dosage to 25 mg every other day.265

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 m2.524 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 m2.524

Monitor closely for hyperkalemia and renal insufficiency.265 (See Hyperkalemia under Cautions.)

Manufacturer recommends holding or discontinuing spironolactone therapy if serum potassium >5 mEq/L or Scr >4 mg/dL.265

ACCF/AHA recommends 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.524

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.524

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 m2.300 If tolerated, may increase dosage to 37.5 mg once daily as clinically indicated.300 If 20-mg daily dosage results in hyperkalemia, may decrease dosage to 20 mg every other day.300

Primary Hyperaldosteronism
Diagnosis
Oral

Tablets: 400 mg daily for 3–4 weeks.265 Correction of hypokalemia and hypertension provides presumptive evidence for the diagnosis of primary hyperaldosteronism.265

Alternatively, 400 mg daily for 4 days.265 If serum potassium concentration increases during spironolactone therapy but decreases when the drug is discontinued, consider presumptive diagnosis of primary hyperaldosteronism.265

Medical Therapy Prior to Adrenalectomy
Oral

Tablets: Patients with a definitive diagnosis: 100–400 mg daily before surgery.265

Treatment Of Primary Hyperaldosteronism
Oral

Tablets: Initially, 400 mg daily.265

Maintenance dosage: 100–300 mg daily.265 Use lowest effective dosage for long-term maintenance therapy.265

Hypokalemia
Oral

Tablets: 25–100 mg daily.265

Hirsutism
Oral

Tablets: 50–200 mg daily.210 Regression of hirsutism evident within 2 months, maximal within 6 months, and has been maintained for ≥16 months with continued therapy.210

Prescribing Limits

Pediatric Patients

Hypertension
Oral

Tablets: Maximum 3.3 mg/kg (up to 100 mg) daily.269

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.524

Heart Failure
Oral

Tablets: ACCF/AHA recommends maximum 50 mg daily.524

Special Populations

Renal Impairment

Manufacturer states that spironolactone is contraindicated in patients with anuria, acute renal insufficiency, or substantial impairment of renal excretory function.265

Heart failure patients with eGFR 30–49 mL/minute per 1.73 m2 (tablets): Initially, 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).524

Heart failure patients with eGFR 30–50 mL/minute per 1.73 m2 (oral suspension [CaroSpir]): Initially, 10 mg once daily.300

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.524

Cautions for Spironolactone

Contraindications

  • Anuria.265

  • Acute renal insufficiency.265

  • Substantial impairment of renal excretory function.265

  • Hyperkalemia.265

  • Known hypersensitivity to spironolactone or any ingredient in the formulation.265

  • Addison's disease.265

  • Concomitant use of eplerenone.265

Warnings/Precautions

Warnings

Hyperkalemia

Avoid concurrent use of potassium supplements.256 265 (See Specific Drugs, Foods, and Laboratory Tests under Interactions.)

Hyperkalemia reported in patients with excess potassium intake and in those with renal insufficiency; hyperkalemia may cause potentially fatal cardiac irregularities.256

Manufacturer recommends monitoring serum potassium and Scr 1 week after initiation or increase in spironolactone dosage, monthly for the first 3 months, then quarterly for a year, and then every 6 months.265 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.524

If hyperkalemia suspected (paresthesia, muscle weakness, fatigue, flaccid paralysis of the extremities, bradycardia, shock), obtain an ECG and monitor serum potassium concentrations.256

If hyperkalemia occurs, immediately discontinue and treat as indicated with parenteral calcium chloride, sodium bicarbonate, and/or oral or parenteral glucose with a rapid acting insulin preparation.256 Consider cationic exchange resins (e.g., sodium polystyrene sulfonate).256 Persistent hyperkalemia may require dialysis.256

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;215 217 218 222 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.218 219 246 247 251 252 253 254

Tumorigenic Effects

Tumorigenic in animals; proliferative effects observed in liver and endocrine organs.256 265 (See Boxed Warning.)

Sensitivity Reactions

Anaphylaxis

Anaphylaxis reported.256 265

Major Toxicities

Fluid and Electrolyte Imbalance

Observe for signs of fluid and electrolyte imbalance (e.g., dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, nausea, vomiting).256

Monitor serum and urine electrolyte concentrations periodically, especially if the patient is vomiting excessively or receiving parenteral fluid therapy.256 265

Minor alterations of fluid and electrolyte balance may precipitate hepatic coma in patients with impaired hepatic function.256 (See Hepatic Impairment under Cautions.)

General Precautions

Dilutional Hyponatremia

Dilutional hyponatremia (dry mouth, thirst, lethargy, and drowsiness) reported; diagnosis confirmed by a low serum sodium concentration.256

Increased risk when spironolactone combined with other diuretics, in edematous patients during hot weather, and in patients with advanced cirrhosis.256

Gynecomastia

Gynecomastia reported; appears related to dose and duration of therapy.256 Risk of gynecomastia may be higher than with eplerenone.1200 Generally reversible upon discontinuance.256

Use of Fixed Combinations

When spironolactone is used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.256

Specific Populations

Pregnancy

Category C.265

Lactation

Metabolite distributed into milk.265 Discontinue nursing or the drug.265

Pediatric Use

Safety and efficacy not fully established.265

Geriatric Use

Monitor serum and urine electrolyte concentrations.265

Hepatic Impairment

Use with caution in patients with impaired hepatic function; minor alterations of fluid and electrolyte balance may precipitate hepatic coma.265

Monitor serum and urine electrolyte concentrations.256 265

Reversible hyperchloremic metabolic acidosis (usually in association with hyperkalemia) reported in patients with decompensated hepatic cirrhosis, even in the presence of normal renal function.265

Renal Impairment

Hyperkalemia reported in patients with impaired renal function.265 (See Contraindications under Cautions and see Renal Impairment under Dosage and Administration.)

Monitor serum and urine electrolyte concentrations periodically.256 265

Transient elevations of BUN reported.265

Common Adverse Effects

Hyperkalemia, hyponatremia, anorexia, nausea, vomiting, diarrhea, abdominal cramping, gastritis, gastric bleeding, ulceration, headache, drowsiness, lethargy, ataxia, mental confusion, fever, rash, anaphylaxis, vasculitis, urticaria, gynecomastia, decreased libido, relative impotence in males, menstrual irregularities, amenorrhea, postmenopausal bleeding, increased BUN concentrations.256 265

Interactions for Spironolactone

Specific Drugs, Foods, and Laboratory Tests

Drug, Food, or Test

Interaction

Comments

ACE inhibitors

Increased risk of severe hyperkalemia265

Monitor serum potassium frequently265 (see Heart Failure under Uses and also under Dosage and Administration)

Alcohol

Potentiation of orthostatic hypotension265

Aldosterone receptor antagonists (e.g., eplerenone)

Increased risk of severe hyperkalemia265

Concomitant use contraindicated265

Angiotensin II antagonists

Increased risk of severe hyperkalemia265

Antihypertensive and hypotensive agents

Additive antihypertensive effectsa

Reduce dosage of antihypertensive agent, especially ganglionic blocking agents, by at least 50% when spironolactone initiateda

Barbiturates

Potentiation of orthostatic hypotension265

Cholestyramine

Hyperkalemic metabolic acidosis reported265

Corticosteroids/ACTH

Possible additive electrolyte depletion, especially potassium265

Monitor serum electrolytes265

Digoxin

Increased serum concentrations of digoxin; possible toxicity265

Monitor for digitalis toxicity; adjust digoxin dosage (maintenance and digitalization)265

Diuretics, potassium-sparing (e.g., amiloride, triamterene)

Increased risk of severe hyperkalemiaa

Concomitant use contraindicateda

Heparin

Increased risk of severe hyperkalemia265

Heparin, low molecular weight

Increased risk of severe hyperkalemia265

Lithium

Reduced renal clearance of lithium; increased risk of lithium toxicity 265

Concomitant use generally contraindicated; if concomitant therapy is necessary, monitor serum lithium concentrations closely and adjust dosage 265

Nondepolarizing neuromuscular blocking agents (e.g., tubocurarine chloride)

Potential increase in neuromuscular blockade265

NSAIAs (e.g., indomethacin, aspirin)

Possible decreased diuretic, natriuretic, and antihypertensive effect; increased risk of severe hyperkalemia265

Use with caution, monitor for diuretic effects265

Monitor for hyperkalemia265

Opiate agonists

Potentiation of orthostatic hypotension265

Potassium supplements and/or foods containing potassium (e.g., salt substitutes, low-salt milk)

Increased risk of severe hyperkalemia 265

Concomitant use generally not recommended265

Test, aldosterone (urinary)

Most methods appear unaffected; metabolites may interfere with radioimmunoassay proceduresa

Test, digoxin (serum)

Possible false elevations with radioimmunoassay procedures; possibly assay specific265

Clinical relevance not fully known265

Tests, steroids

Cortisol (17-hydroxycorticosteroids, plasma and urinary)

17-hydroxycorticosteroids (urinary, Porter-Silber technique)

17-ketosteroids, 17-ketogenic steroids, (urinary, Klendshoj, Feldstein and Sprague technique)

Spironolactone metabolites fluoresce; may interfere with fluorometric analysisa

Clinical relevance not fully known265

Vasopressors (e.g., norepinephrine)

Possible decreased vascular response265

Use anesthesia (regional or general) with caution265

Spironolactone Pharmacokinetics

Absorption

Well absorbed following oral administration.300 Peak serum concentrations of spironolactone usually attained within 1–2 or 0.5–1.5 hours with oral tablets or oral suspension (CaroSpir), respectively;200 201 265 300 peak serum concentrations of the principal metabolites (e.g., canrenone) usually attained within 2–4 hours (tablets)265 or 2.5–5 hours (oral suspension [CaroSpir]).300 Serum concentrations of spironolactone 15–37% higher following oral suspension (CaroSpir) than with oral tablets (Aldactone)300 .

Bioavailability

>90%.300 a

Onset

Gradual; maximum diuretic effect reached on third day.a

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

Duration

Diuresis persists for 2–3 days after discontinuance.a

Food

Food increases peak serum concentrations and AUC.265 300

Distribution

Extent

Spironolactone and its metabolites crosses the placenta.

Canrenone, a major active metabolite, is distributed into milk.256

Plasma Protein Binding

Spironolactone and canrenone: >90%.265 300

Elimination

Metabolism

Rapidly and extensively metabolized; canrenone and/or 7α-thiomethylspironolactone appear to be major active metabolites.200 201 256 300

Undergoes hepatic deacetylation, thiomethylation, and hydroxylation.200 201 300

Elimination Route

Excreted principally in urine as metabolites and to a lesser extent in bile.265 300

Half-life

Spironolactone: 1.4 hours.265

Metabolites: 13.8–16.5 hours.265

Stability

Storage

Oral

Tablets

<25°C.256 265

Suspension

CaroSpir: 20–25°C (may be exposed to 15–30°C)300

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

Actions

  • Synthetic steroid mineralocorticoid receptor antagonist (aldosterone antagonist).215 256 265 266

  • Exhibits magnesium- and potassium-sparing,224 230 233 natriuretic,232 247 diuretic,224 232 and hypotensive215 224 225 227 effects by competitively inhibiting the physiologic effects of the adrenocortical hormone aldosterone on the distal renal tubules, myocardium,225 226 228 232 and vasculature.232 233 265

  • Generally does not cause potassium depletion or affect glucose metabolism or uric acid excretion.265

  • Androgen and progesterone receptor antagonist.206 208 209 210 211 215 256 265 266 267 268

Advice to Patients

  • Importance of advising patient to avoid excessive ingestion of potassium supplements, potassium-rich foods, or salt substitutes.256

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.265

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.265

  • Importance of informing patients of other important precautionary information.265 (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

Spironolactone

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Suspension

25 mg/mL

CaroSpir

CMP

Tablets, film-coated

25 mg*

Aldactone

Pfizer

Spironolactone Tablets

50 mg*

Aldactone (scored)

Pfizer

Spironolactone Tablets

100 mg*

Aldactone (scored)

Pfizer

Spironolactone Tablets

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

Spironolactone and Hydrochlorothiazide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

25 mg Spironolactone and Hydrochlorothiazide 25 mg*

Aldactazide

Pfizer

Spironolactone and Hydrochlorothiazide Tablets

50 mg Spironolactone and Hydrochlorothiazide 50 mg

Aldactazide (scored)

Pfizer

AHFS DI Essentials™. © Copyright 2019, Selected Revisions May 6, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

200. Overdiek HWPM, Merkus FWHM. Influence of food on the bioavailability of spironolactone. Clin Pharmacol Ther. 1986; 40:531-6. http://www.ncbi.nlm.nih.gov/pubmed/3769384?dopt=AbstractPlus

201. Overdiek HWPM, Hermens WAJJ, Merkus FWHM. New insights into the pharmacokinetics of spironolactone. Clin Pharmacol Ther. 1985; 38:469-74. http://www.ncbi.nlm.nih.gov/pubmed/4042530?dopt=AbstractPlus

202. Wathen CG, MacDonald T, Wise LA et al. Eosinophilia associated with spironolactone. Lancet. 1986; 1:919-20. http://www.ncbi.nlm.nih.gov/pubmed/2870390?dopt=AbstractPlus

203. Laue L, Kenigsberg D, Pescovitz OH et al. Treatment of familial male precocious puberty with spironolactone and testolactone. N Engl J Med. 1989; 320:496-502. http://www.ncbi.nlm.nih.gov/pubmed/2492636?dopt=AbstractPlus

204. Laue L, Jones J, Barnes KM et al. Treatment of familial male precocious puberty with spironolactone, testolactone, and desorelin. J Clin Endocrinol Metab. 1993; 76:151-5. http://www.ncbi.nlm.nih.gov/pubmed/8421081?dopt=AbstractPlus

205. Kaplan SL, Grumbach MM. Pathophysiology and treatment of sexual precocity. J Clin Endocrinol Metab. 1990; 71:785-9. http://www.ncbi.nlm.nih.gov/pubmed/2205623?dopt=AbstractPlus

206. Stein DT. Southwestern Internal Medicine Conference: new developments in the diagnosis and treatment of sexual precocity. Am J Med Sci. 1992; 303:53-71. http://www.ncbi.nlm.nih.gov/pubmed/1728875?dopt=AbstractPlus

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