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Management of edema associated with excessive aldosterone excretion or with congestive heart failure (HF) unresponsive to other therapies; hypertension; primary hyperaldosteronism (establishing diagnosis, short-term preoperative treatment, and long-term maintenance therapy in selected patients); hypokalemia; cirrhosis of liver accompanied by edema or ascites; nephrotic syndrome; severe HF (NYHA class III-IV) to increase survival and reduce hospitalization when added to standard therapy
Note: The ACCF/AHA 2013 heart failure guidelines recommend the use of aldosterone antagonists, along with other guideline-directed medical therapies, to reduce morbidity and mortality in patients with HF (NYHA class III-IV) with LVEF ≤35% (Yancy 2013).
According to the Eighth Joint National Committee (JNC 8) guidelines, aldosterone antagonists are not recommended for the initial treatment of hypertension (James 2013).
According to the 2013 ACCF/AHA guidelines for the management of ST-elevation myocardial infarction (STEMI) and the guidelines for the management of unstable angina/non-STEMI, an aldosterone antagonist should be given to patients who are already on an ACE inhibitor and beta-blocker, who have an LVEF ≤40% and either symptomatic HF or diabetes mellitus (ACCF/AHA [Anderson 2013]; ACCF/AHA [O 'Gara 2013]).
Anuria; acute renal insufficiency; significant impairment of renal excretory function; hyperkalemia; Addison 's disease; concomitant use with eplerenone
Canadian labeling: Additional contraindications (not in U.S. labeling): Hypersensitivity to spironolactone or any component of the formulation; concomitant use with heparin or low molecular weight heparin
Spironolactone has been shown to be a tumorigen in chronic toxicity studies in rats. Use spironolactone only in those conditions for which it is indicated. Avoid unnecessary use of this drug.
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.
Ascites, due to cirrhosis (off-label dose): Initial: 100 mg once daily; titrate every 3 to 5 days as clinically indicated (usual maximum: 400 mg once daily) (Runyon 2013)
Edema: Oral: 25 to 200 mg daily in 1 to 2 divided doses
Hypokalemia: Oral: 25 to 100 mg once daily
Hypertension: Oral: Initial: The manufacturer 's labeling recommends 50 to 100 mg in 1 to 2 divided doses; after 2 weeks, may adjust dose. In patients with resistant hypertension, an initial daily dose of 25 mg may also be added to other antihypertensive agents with an increase to 50 mg daily if needed (Vaclavik 2014; Williams 2015). Usual dosage range (ASH/ISH [Weber 2014]): 25 to 50 mg daily
Diagnosis of primary aldosteronism: Oral: Long test: 400 mg once daily for 3 to 4 weeks; short test: 400 mg once daily for 4 days; maintenance until surgical correction: 100 to 400 mg once daily
Heart failure, severe (NYHA class III-IV): Oral: Initial: 12.5 to 25 mg once daily; maximum daily dose: 50 mg. If 25 mg once daily not tolerated, may reduce to 25 mg every other day. The ACCF/AHA 2013 HF guidelines also recommend the use of aldosterone receptor antagonists (eg, spironolactone) in patients with NYHA class II HF and LVEF ≤35% who have a history of prior cardiovascular hospitalization or elevated plasma natriuretic peptide levels and postmyocardial infarction patients with LVEF ≤40% who develop HF symptoms or have a history of diabetes mellitus (ACCF/AHA [Yancy 2013]).
Note: Per the manufacturer, if potassium >5 mEq/L or serum creatinine >4 mg/dL, discontinue or interrupt therapy. Alternatively, the ACCF/AHA 2013 HF guidelines recommend withholding treatment if potassium >5.5 mEq/L or renal function worsens; hold doses until potassium is <5 mEq/L and consider restarting with a reduced dose after confirming resolution of hyperkalemia/renal insufficiency for at least 72 hours (ACCF/AHA [Yancy 2013]).
Acne in women (off-label use): Oral: 50 to 200 mg once daily (Goodfellow 1984; Muhlemann 1986)
Hirsutism in women (off-label use): Oral: 50 to 200 mg daily in 1 to 2 divided doses (Koulouri 2008; Martin 2008)
Hypertension: Oral: No initial dosage adjustment necessary (Aronow 2011).
Administration with food increases absorption. 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.
Edema, hypertension (off-label use): Oral: Children 1-17 years: Initial: 1 mg/kg/day divided every 12 to 24 hours (maximum dose: 3.3 mg/kg/day, up to 100 mg daily) (NHBPEP 2004)
Manufacturer 's labeling: Contraindicated in patients with anuria, acute renal insufficiency, or significant impairment of renal excretory function.
Alternate recommendations:
Heart failure (ACCF/AHA [Yancy 2013]):
eGFR ≥50 mL/minute/1.73 m2: Initial dose: 12.5-25 mg once daily; Maintenance dose (after 4 weeks of treatment with potassium ≤5 mEq/L): 25 mg once or twice daily
eGFR 30-49 mL/minute/1.73 m2: Initial dose: 12.5 mg once daily or every other day; Maintenance dose (after 4 weeks of treatment with potassium ≤5 mEq/L): 12.5-25 mg once daily
eGFR <30 mL/minute/1.73 m2: Not recommended.
Geriatric patients ≥65 years: CrCl <30 mL/minute (regardless of indication): Avoid use due to risk of hyperkalemia (Beers Criteria [AGS 2015]).
There are no dosage adjustments provided in manufacturer 's labeling.
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.
Store below 25 ‚ °C (77 ‚ °F).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Aldactone: 25 mg
Aldactone: 50 mg, 100 mg [scored]
Generic: 25 mg, 50 mg, 100 mg
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 2]).
A 1 mg/mL oral suspension may be made with tablets. Crush ten 25 mg tablets in a mortar and reduce to a fine powder. Add a small amount of purified water and soak for 5 minutes; add 50 mL 1.5% carboxymethylcellulose, 100 mL syrup NF, and mix to a uniform paste; mix while adding purified water in incremental proportions to almost 250 mL; transfer to a calibrated bottle, rinse mortar with purified water, and add quantity of purified water sufficient to make 250 mL. Label shake well". Stable for 3 months at room temperature or refrigerated (Nahata 1993).
A 2.5 mg/mL oral suspension may be made with tablets. Crush twelve 25 mg tablets in a mortar and reduce to a fine powder. Add small portions of distilled water or glycerin and mix to a uniform paste; mix while adding cherry syrup to almost 120 mL; transfer to a calibrated bottle, rinse mortar with cherry syrup, and add quantity of cherry syrup sufficient to make 120 mL. Label shake well" and "refrigerate". This method may also be used with twenty-four 25 mg tablets for a 5 mg/mL oral suspension. Both concentrations are stable for 28 days refrigerated (Mathur 1989).
A 25 mg/mL oral suspension may be made with tablets and either a 1:1 mixture of Ora-Sweet and Ora-Plus or a 1:1 mixture of Ora-Sweet SF and Ora-Plus. Crush one-hundred-twenty 25 mg tablets in a mortar and reduce to a fine powder. Add small portions of chosen vehicle and mix to a uniform paste; mix while adding vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Store in amber bottles; label shake well" and "refrigerate". Stable for 60 days refrigerated (Allen 1996).
Allen LV Jr and Erickson MA 3rd, "Stability of Ketoconazole, Metolazone, Metronidazole, Procainamide Hydrochloride, and Spironolactone in Extemporaneously Compounded Oral Liquids," Am J Health Syst Pharm. 1996, 53(17):2073-8.[PMID: 8870895]Mathur LK and Wickman A, "Stability of Extemporaneously Compounded Spironolactone Suspensions," Am J Hosp Pharm. 1989, 46(10):2040-2.[PMID: 2816959]Nahata MC, Morosco RS, and Hipple TF, "Stability of Spironolactone in an Extemporaneously Prepared Suspension at Two Temperatures," Ann Pharmacother. 1993, 27(10):1198-9.[PMID: 8251687]Abiraterone Acetate: Spironolactone may diminish the therapeutic effect of Abiraterone Acetate. Monitor therapy
ACE Inhibitors: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Alpha-/Beta-Agonists: Spironolactone may diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification
AMILoride: May enhance the hyperkalemic effect of Spironolactone. Avoid combination
Ammonium Chloride: Potassium-Sparing Diuretics may enhance the adverse/toxic effect of Ammonium Chloride. Specifically the risk of systemic acidosis. Consider therapy modification
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Analgesics (Opioid): May enhance the adverse/toxic effect of Diuretics. Analgesics (Opioid) may diminish the therapeutic effect of Diuretics. Monitor therapy
Angiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy
AtorvaSTATin: May enhance the adverse/toxic effect of Spironolactone. Specifically, there is a theoretical potential for enhanced effects on reducing endogenous steroid activity. Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Canagliflozin: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Canagliflozin may enhance the hypotensive effect of Potassium-Sparing Diuretics. Monitor therapy
Cardiac Glycosides: Potassium-Sparing Diuretics may diminish the therapeutic effect of Cardiac Glycosides. In particular, the inotropic effects of digoxin appear to be diminished. Potassium-Sparing Diuretics may increase the serum concentration of Cardiac Glycosides. This particular effect may be unique to Spironolactone. Monitor therapy
Cholestyramine Resin: May enhance the adverse/toxic effect of Spironolactone. Specifically, the risks of developing metabolic acidosis and hyperkalemia may be elevated with this combination. Monitor therapy
Ciprofloxacin (Systemic): Spironolactone may enhance the arrhythmogenic effect of Ciprofloxacin (Systemic). Monitor therapy
CycloSPORINE (Systemic): Potassium-Sparing Diuretics may enhance the hyperkalemic effect of CycloSPORINE (Systemic). Avoid combination
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Digoxin: Spironolactone may increase the serum concentration of Digoxin. Spironolactone (and/or its metabolites) may also interfere with the assays used to determine Digoxin concentrations, falsely increasing or decreasing Digoxin concentrations. Monitor therapy
Drospirenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy
Eplerenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: This combination is contraindicated in patients receiving eplerenone for treatment of hypertension. Consider therapy modification
Heparin: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: Monitor serum potassium concentrations closely. The spironolactone Canadian product monograph lists its combination with heparin or low molecular weight heparins as contraindicated. Monitor therapy
Heparin (Low Molecular Weight): May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: Monitor serum potassium concentrations closely. The spironolactone Canadian product monograph lists its combination with heparin or low molecular weight heparins as contraindicated. Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Mitotane: Spironolactone may diminish the therapeutic effect of Mitotane. Management: Consideration should be given to discontinuing spironolactone prior to initiating mitotane in order to eliminate the risk of therapeutic failure of the mitotane. Consider therapy modification
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Neuromuscular-Blocking Agents (Nondepolarizing): Spironolactone may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicorandil: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nitrofurantoin: May enhance the hyperkalemic effect of Spironolactone. Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
QuiNIDine: Potassium-Sparing Diuretics may diminish the therapeutic effect of QuiNIDine. Monitor therapy
Sodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with diuretics, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, hydrate adequately and monitor fluid and renal status. Consider therapy modification
Tacrolimus (Systemic): Potassium-Sparing Diuretics may enhance the hyperkalemic effect of Tacrolimus (Systemic). Avoid combination
Tolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy
Triamterene: May enhance the hyperkalemic effect of Spironolactone. Avoid combination
Trimethoprim: May enhance the hyperkalemic effect of Spironolactone. Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Blood pressure, serum electrolytes (potassium, sodium), renal function, I & O ratios and daily weight throughout therapy
ACCF/AHA heart failure guideline recommendations (ACCF/AHA [Yancy 2013]): Serum potassium and renal function should be checked in 3 days after initiation, at 1 week after initiation, at least monthly for the first 3 months of therapy, and every 3 months thereafter. If adding or increasing the dose of concomitant ACE inhibitors or ARBs, a new cycle of monitoring should be done. If serum potassium increases to >5.5 mEq/L or renal function worsens, hold doses until potassium is <5 mEq/L and consider restarting with a reduced dose after confirming resolution of hyperkalemia/renal insufficiency for at least 72 hours.
May interfere with the radioimmunoassay for digoxin.
Frequency not defined.
Cardiovascular: Vasculitis
Central nervous system: Ataxia, confusion, drowsiness, headache, lethargy
Dermatologic: Erythematous maculopapular rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
Endocrine & metabolic: Amenorrhea, gynecomastia, hyperkalemia
Gastrointestinal: Abdominal cramps, diarrhea, gastritis, gastrointestinal hemorrhage, gastrointestinal ulcer, nausea, vomiting
Genitourinary: Impotence, irregular menses, postmenopausal bleeding
Hematologic & oncologic: Agranulocytosis, malignant neoplasm of breast
Hepatic: Hepatotoxicity
Hypersensitivity: Anaphylaxis
Immunologic: DRESS syndrome
Renal: Increased blood urea nitrogen, renal failure, renal insufficiency
Miscellaneous: Fever
Concerns related to adverse effects:
- CNS effects: Somnolence and dizziness have been reported with use; advise patients to use caution when driving or operating machinery until response to initial treatment has been determined.
- Fluid/electrolyte loss: Excess amounts can lead to profound diuresis with fluid and electrolyte loss; close medical supervision and dose evaluation are required. Watch for and correct electrolyte disturbances; adjust dose to avoid dehydration.
- Gynecomastia: Related to dose and duration of therapy; typically is reversible following discontinuation of therapy but may persist (rare).
- Hyperkalemia: Monitor closely for hyperkalemia; increases in serum potassium are dose related and rates of hyperkalemia also increase with declining renal function. The concurrent use of larger doses of ACE inhibitors (eg, ≥ lisinopril 10 mg daily in adults) also increases the risk of hyperkalemia (ACCF/AHA [Yancy 2013]). Dose reduction or interruption of therapy may be necessary with development of hyperkalemia. Use is contraindicated in patients with hyperkalemia; use caution in conditions known to cause hyperkalemia.
- Tumorigenic: [US Boxed Warning]: Shown to be a tumorigen in chronic toxicity animal studies. Avoid unnecessary use.
Disease-related concerns:
- Adrenal vein catheterization: Discontinue use prior to adrenal vein catheterization.
- Cirrhosis: In cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy.
- Heart failure: When evaluating a heart failure patient for spironolactone treatment, eGFR should be >30 mL/minute/1.73 m2 or creatinine should be ≤2.5 mg/dL (men) or ≤2 mg/dL (women) with no recent worsening and potassium <5 mEq/L with no history of severe hyperkalemia (ACCF/AHA [Yancy 2013]). Serum potassium levels require close monitoring and management if elevated. The manufacturer recommends to discontinue or interrupt therapy if serum potassium >5 mEq/L or serum creatinine >4 mg/dL. The ACCF/AHA recommends considering discontinuation upon the development of serum potassium >5.5 mEq/L or worsening renal function with careful evaluation of the entire medical regimen. Avoid routine triple therapy with the combined use of an ACE inhibitor, ARB, and spironolactone. Instruct patients with heart failure to discontinue use during an episode of diarrhea or dehydration or when loop diuretic therapy is interrupted (ACCF/AHA [Yancy 2013]).
- Renal impairment: Risk of hyperkalemia is increased with declining renal function and with the concurrent use of larger doses of ACE inhibitors (eg, ≥ lisinopril 10 mg daily in adults) (ACCF/AHA [Yancy 2013]). Use with caution in patients with mild renal impairment; contraindicated with anuria, acute renal insufficiency, or significant impairment of renal excretory function.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Elderly: Avoid use of doses >25 mg/day in elderly patients with heart failure or with reduced renal function (eg, CrCl <30 mL/minute or eGFR ≤30 mL/minute/1.73 m2 [Yancy 2013]).
- Ethanol use: Concurrent use with ethanol may Increase risk of orthostasis.
Special handling:
- Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 2]).
C
Adverse events were observed in some animal reproduction studies. The antiandrogen effects of spironolactone have been shown to cause feminization of the male fetus in animal studies. Spironolactone crosses the placenta (Regitz-Zagrosek 2011).
The treatment of heart failure is generally the same in pregnant and nonpregnant women; however, spironolactone should be avoided in the first trimester due to its antiandrogenic effects (Regitz-Zagrosek 2011). The use of mineralocorticoid receptor antagonists is not recommended to treat chronic uncomplicated hypertension in pregnant women and should generally be avoided in women of reproductive potential. When treatment for hypertension in pregnancy is needed, other agents are preferred (ACOG 2013). Use of diuretics to treat edema during normal pregnancies is not appropriate; use may be considered when edema is due to pathologic causes (as in the nonpregnant patient); monitor.
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
Hepatic to multiple metabolites, including active metabolites canrenone and 7-alpha-spirolactone
Urine and feces
Serum: 3-4 hours (primarily as the active metabolite)
2-3 days
Spironolactone: ~1.4 hours; Canrenone: 12-20 hours (Skluth 1990); 7-alpha-spirolactone: ~13.8 hours
>90%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience diarrhea, fatigue, headache, nausea, vomiting, or abdominal cramps. Have patient report immediately to prescriber signs of fluid and electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, nausea, or vomiting), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any bleeding that is very bad or that will not stop), severe dizziness, passing out, confusion, change in balance, sexual dysfunction, chills, pharyngitis, burning or numbness feeling, bradycardia, urinary retention, change in amount of urine passed, menstrual irregularities, breast pain, or male enlarged breasts (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.