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Aldactone

Pronunciation

Generic Name: Spironolactone
Class: Mineralocorticoid (Aldosterone) Receptor Antagonists
VA Class: CV704
CAS Number: 52-01-7

Warning(s)

  • Tumorigenic in chronic toxicity studies in rats.256 265 Use for FDA-approved indications; 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 Aldactone

Edema

Management of edema associated with excessive aldosterone including cirrhosis of the liver and nephrotic syndrome.256

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

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents);256 262 265 used for patients who cannot be treated adequately with other agents or for whom other agents are considered inappropriate.265

One of several initial preferred therapies in hypertensive patients with heart failure and in those with ischemic heart disease (e.g., MI).262

Can be used as monotherapy for initial management of uncomplicated hypertension; however, thiazide diuretics are preferred by JNC 7.262

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CHF

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

Has been used in conjunction with ACE inhibitors, loop diuretics, and occasionally cardiac glycosides in patients with severe CHF whose condition was inadequately controlled by an ACE inhibitor and a loop diuretic.215 216 217 226 247

Consider adding spironolactone to standard therapy in patients with severe (i.e., NYHA class IV) CHF.246 247

Safety and efficacy in mild or moderate CHF not determined.246 247

Primary Aldosteronism

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

Short-term preoperative treatment of primary aldosteronism.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 a

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

Aldactone Dosage and Administration

Administration

Administer orally.256 265

Oral Administration

Administer as single or divided doses; 2 doses daily may be adequate.262 265 a

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
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
Oral

Initially, 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 Aldosteronism
Diagnosis
Oral

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 aldosteronism should be considered.265

Adults

Edema
Oral

Initially, 100 mg daily.265 Range: 25–200 mg daily.265

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

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

Spironolactone in combination with hydrochlorothiazide: 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

Lower dosage and combination therapy recommended by JNC 7; higher spironolactone dosage may result in intolerable adverse effects.262

Carefully monitor BP during initial titration or subsequent upward adjustment in dosage.214 262

Adjust dosage at approximately monthly intervals.214 262

Monotherapy
Oral

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

Usual dosage recommended by JNC 7: 25–50 mg daily.262

Spironolactone/Hydrochlorothiazide 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 sprionolactone/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

CHF
Oral

Initially, 12.5–25 mg daily used in patients receiving an ACE inhibitor and a loop diuretic with or without a cardiac glycoside.215 216 246 247

Increase to 50 mg daily after 8 weeks in patients who exhibit signs and symptoms of progressive heart failure and have serum potassium concentrations <5.5 mEq/L.215

Decrease to 25 mg every other day if hyperkalemia occurs.215 216

Primary Aldosteronism
Diagnosis
Oral

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

Medical Therapy Prior to Adrenalectomy
Oral

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

Treatment Of Primary Aldosteronism
Oral

Initially, 400 mg daily.265

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

Hypokalemia
Oral

25–100 mg daily.265

Hirsutism
Oral

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

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

Cautions for Aldactone

Contraindications

  • Anuria.265

  • Acute renal insufficiency265

  • Substantial impairment of renal excretory function.265

  • Hyperkalemia.265

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

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 CHF 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 a

Gynecomastia

Gynecomastia reported; appears related to dose and duration of therapy.256 Generally reversible upon discontinuance.256

Use of Fixed Combinations

When spirolactone 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.)

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 a

Interactions for Aldactone

Specific Drugs, Foods, and Laboratory Tests

Drug, Food, or Test

Interaction

Comments

ACE inhibitor

Increased risk of hyperkalemia265

Monitor serum potassium frequently265 (See CHF under Uses and also under Dosage and Administration)

Alcohol

Potentiation of orthostatic hypotension265

Antihypertensive and hypotensive agents

Additive antihypertensive effectsa

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

Barbiturates

Potentiation of orthostatic hypotension265

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 hyperkalemiaa

Concomitant use contraindicateda

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 hyperkalemia265

Use with caution, monitor for diuretic effects265 a

Monitor for hyperkalemia265

Opiate agonists

Potentiation for orthostatic hypotension265

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

Increased risk of 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

Aldactone Pharmacokinetics

Absorption

Well absorbed following oral administration; peak serum concentrations of spironolactone usually attained within 1–2 hours;200 201 peak serum concentrations of the principal metabolites200 201 usually attained within 2–4 hours.a

Bioavailability

>90%.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; clinical importance not known.200

Distribution

Extent

Spironolactone and its metabolites crosses the placenta.

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

Plasma Protein Binding

Spironolactone and canrenone: >90%.265

Elimination

Metabolism

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

Undergoes hepatic deacetylation, thiomethylation, and hydroxylation.200 201

Elimination Route

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

Half-life

Spironolactone: 1.4 hours.265

Metabolites: 13.8–16.5 hours.265

Stability

Storage

Oral

Tablets

<25°C.256 265

Suspension

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 adrenocorticortical 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.

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

Spironolactone

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

25 mg*

Aldactone (with povidone)

Pfizer

Spironolactone Tablets

Mutual, Mylan, Sandoz, UDL, United Research

50 mg*

Aldactone (with povidone; scored)

Pfizer

Spironolactone Tablets

Mutual, Mylan, Purepac, United Research

100 mg*

Aldactone (with povidone; scored)

Pfizer

Spironolactone Tablets

Mutual, Mylan, Purepac, United Research

* 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

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Aldactazide 25-25MG Tablets (PFIZER U.S.): 30/$41.99 or 90/$103.97

Aldactazide 50-50MG Tablets (PFIZER U.S.): 30/$67.99 or 90/$187.97

Aldactone 100MG Tablets (PFIZER U.S.): 30/$97.99 or 90/$279.98

Aldactone 25MG Tablets (PFIZER U.S.): 30/$39.99 or 90/$101.97

Aldactone 50MG Tablets (PFIZER U.S.): 30/$65.99 or 90/$175.97

Spironolactone 100MG Tablets (MYLAN): 30/$51.99 or 90/$123.97

Spironolactone 25MG Tablets (ACTAVIS ELIZABETH): 30/$15.99 or 60/$22.98

Spironolactone 50MG Tablets (MUTUAL PHARMACEUTICAL): 30/$21.99 or 90/$46.97

Spironolactone-HCTZ 25-25MG Tablets (MYLAN): 30/$16.99 or 60/$23.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions October 1, 2005. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, 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.

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