Note: Although spironolactone is commercially available in a suspension, it is NOT therapeutically equivalent to the tablets; commercially available suspension results in 15% to 37% higher serum concentration compared to the tablet; pediatric dosing is based on experience with tablets and extemporaneously compounded suspension. Multiple concentrations of oral suspension exist; use extra precaution and prescribe in mg (not mL).
Bronchopulmonary dysplasia (BPD): Limited data available; efficacy results variable. Although the benefits of diuretic therapy in the management of BPD are variable (eg, optimal duration of therapy, impact on pulmonary endpoints), diuretics continue to be used in clinical practice (Slaughter 2013): Oral: 1.5 mg/kg/dose every 12 hours; used in combination with a thiazide diuretic (Albersheim 1989; Engelhardt 1989; Hoffman 2000; Stewart 2011); used most often in preterm neonates at a PNA >28 days (Slaughter 2013)
Edema (diuresis): Limited data available: Oral: 1 to 3 mg/kg/day in divided doses every 12 to 24 hours; used in combination with a thiazide diuretic (Eichenwald 2017; Fanaroff 2013; van der Vorst 2006)
Dosing adjustment in renal impairment: Spironolactone is substantially excreted by the kidney; use with caution; monitor serum potassium closely; consider extended dosing intervals (eg, every 24 to 48 hours) for moderate renal impairment; avoid use in severe renal impairment (van der Vorst 2006)
Note: Although spironolactone is commercially available in a suspension, it is NOT therapeutically equivalent to the tablets; commercially available suspension results in 15% to 37% higher serum concentration compared to the tablet; pediatric dosing is based on experience with tablets and extemporaneously compounded suspension. Multiple concentrations of oral suspension exist; use extra precaution and prescribe in mg (not mL).
Bronchopulmonary dysplasia (BPD): Limited data available; efficacy results variable. Although the benefits of diuretic therapy in the management of BPD are variable (eg, optimal duration of therapy, impact on pulmonary endpoints), diuretics continue to be used in clinical practice (Slaughter 2013). Infants: Oral: 1.5 mg/kg/dose every 12 hours (Albersheim 1989; Engelhardt 1989; Hoffman 2000; Stewart 2011).
Edema (diuresis): Limited data available: Infants, Children, and Adolescents: Oral: Initial: 1 to 3 mg/kg/day divided every 6 to 24 hours; titrate as needed; reported maximum daily dose range: 4 to 6 mg/kg/day in divided doses every 6 to 12 hours or 400 mg/day, whichever is less (Giefer 2011; Kliegman 2016; Sabri 2003; van der Vorst 2006)
Hypertension: Limited data available: Infants, Children, and Adolescents: Oral: Initial: 1 mg/kg/day divided every 12 to 24 hours; titrate as needed up to a maximum daily dose: 3.3 mg/kg/day or 100 mg/day, whichever is less (NHBPEP 2004; Park 2014)
Primary aldosteronism (caused by adrenal hyperplasia), treatment: Limited data available: Infants, Children, and Adolescents: Oral: 1 to 3 mg/kg/day; maximum daily dose: 100 mg/day (Kliegman 2016)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; spironolactone is substantially excreted by the kidney; use with caution; monitor serum potassium closely. The following recommendations have been suggested: In pediatric patients with mild to moderate failure, consider extended dosing interval (eg, every 12 to 24 hours) and avoid use in severe renal impairment (van der Vorst 2006).
There are no dosage adjustments provided in the manufacturer's labeling. Use with caution; minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
(For additional information see "Spironolactone: Drug information")
Note: Suspension is not therapeutically equivalent to tablets. Suspension results in 15% to 37% higher serum concentration compared to tablets. Doses of suspension >100 mg may result in higher than expected serum concentrations. In patients requiring >100 mg/dose, use tablets only.
Acne vulgaris, females (alternative agent) (off-label use):
Tablet: Oral: Initial: 25 to 50 mg/day in 1 to 2 divided doses; titrate as needed based on response and tolerability to a usual effective dose of 50 to 100 mg/day in 1 to 2 divided doses; maximum dose: 200 mg/day (AAD [Zaenglein 2016]; Goodfellow 1984; Graber 2021; Muhlemann 1986; Shaw 2000; Yemisci 2005).
Ascites due to cirrhosis:
Note: Generally used in combination with furosemide, but may be used as monotherapy for patients with hypokalemia. For combination therapy, a dosing ratio of spironolactone 100 mg to furosemide 40 mg should generally be maintained, but can be adjusted for electrolyte abnormalities (AASLD [Runyon 2013]; Runyon 2020).
Tablet: Oral: Initial: 100 mg once daily; titrate every 3 to 5 days based on response and tolerability; usual maximum dose: 400 mg once daily (AASLD [Runyon 2013]; Runyon 2020). For small-volume ascites in patients who weigh ≤50 kg, some experts recommend a starting dose of 50 mg once daily (Runyon 2020).
Heart failure:
Note: When initiating therapy, verify the following: serum creatinine ≤2.5 mg/dL in men and ≤2 mg/dL in women or eGFR >30 mL/minute/1.73 m2 and serum potassium <5 mEq/L. Monitor closely and if patient develops hyperkalemia (serum potassium >5.5 mEq/L), reduce the dose, change to every-other-day dosing, or discontinue therapy; assess for other causes of hyperkalemia before permanent discontinuation. If renal function worsens, consider dose reduction or discontinuation (ACC [Maddox 2021]; ACC/AHA [Yancy 2017]; ACCF/AHA [Yancy 2013]).
Heart failure with preserved ejection fraction (off-label use):
Note: May be considered for use in patients with symptomatic heart failure with preserved ejection fraction (≥45%) who have an elevated serum natriuretic peptide level or have been hospitalized for heart failure in the last 12 months (ACC/AHA [Yancy 2017]; Pitt 2014). Some experts recommend initiating therapy only if serum potassium is ≤4.7 mEq/L and eGFR is ≥30 mL/minute/1.73 m2. The same experts recommend dose reduction when serum potassium is >5 mEq/L and discontinuation when serum potassium is >5.5 mEq/L (Borlaug 2020).
Tablet: Oral: Initial: 12.5 mg once daily; may double the dose every 4 weeks if serum potassium remains <5 mEq/L and renal function is stable, up to a maximum target dose of 50 mg/day in 1 or 2 divided doses (ACC/AHA [Yancy 2017]; Borlaug 2020; Pitt 2014). Some experts recommend up-titrating therapy only if serum potassium is ≤4.5 mEq/L (Borlaug 2020).
Heart failure with reduced ejection fraction:
Note: Should be considered for use in patients with symptomatic (New York Heart Association class II to IV) heart failure with reduced ejection fraction (HFrEF) (≤35%) as part of an optimal medical regimen for HFrEF (ACC/AHA [Yancy 2017]; ACCF/AHA [Yancy 2013]).
Tablet: Oral: Initial: 12.5 to 25 mg once daily; may double the dose every 4 weeks if serum potassium remains <5 mEq/L and renal function is stable, up to a maximum target dose of 50 mg/day in 1 to 2 divided doses (ACC/AHA [Yancy 2017]; ACCF/AHA [Yancy 2013]; Pitt 1999).
Suspension: Oral: Initial: 10 to 20 mg once daily. Consider a starting dose of 10 mg once daily in patients at increased risk of hyperkalemia. May titrate to 37.5 mg once daily if serum potassium remains <5 mEq/L and renal function is stable (ACCF/AHA [Yancy 2013]; Colucci 2021; manufacturer labeling).
Post-myocardial infarction, complicated by reduced ejection fraction (off-label use):
Note: Should be considered for use following acute myocardial infarction (MI) in patients with left ventricular ejection fraction ≤40% plus symptoms of heart failure or diabetes. Use in addition to other pharmacologic therapies post MI (ACCF/AHA [O’Gara 2013]; ACCF/AHA [Yancy 2013]).
Tablet: Oral: Initial: 12.5 to 25 mg once daily; may double the dose every 4 weeks if serum potassium remains <5 mEq/L and renal function is stable, up to a maximum target dose of 50 mg/day in 1 to 2 divided doses (ACCF/AHA [Yancy 2013]).
Suspension: Oral: Initial: 10 to 20 mg once daily. Consider a starting dose of 10 mg once daily in patients at increased risk of hyperkalemia. May titrate to 37.5 mg once daily if serum potassium remains <5 mEq/L and renal function is stable (ACCF/AHA [Yancy 2013]; Colucci 2021).
Hirsutism, females (alternative agent) (off-label use):
Note: Typically given in addition to oral contraceptives (OCs) if inadequate response to OCs is observed after 6 months. May be considered as initial therapy for females who cannot conceive or who are using reliable contraception (Barbieri 2021; ES [Martin 2018]).
Tablet: Oral: Initial: 50 mg twice daily; may increase to 100 mg twice daily as needed. Assess response at 6-month intervals before adjusting dose, adding additional agents, or switching to alternative therapy (Barbieri 2021; ES [Martin 2018]).
Hormone therapy for transgender females, male-to-female (adjunctive agent) (off-label use):
Tablet: Oral: Initial: 25 mg once or twice daily in combination with other appropriate agents. Increase at 1-week intervals based on response and tolerability to a usual dose of 100 to 300 mg/day in 2 divided doses; maximum dose: 400 mg/day. Adjust dose with a goal of suppressing serum testosterone levels into the normal range for females (<50 ng/dL) (Deutsch 2016; ES [Hembree 2017]; Prior 1989).
Hypertension, chronic (alternative agent):
Note: Not recommended for initial management but may be considered as additional therapy for resistant hypertension in patients who do not respond adequately to combination therapy with preferred agents (ACC/AHA [Whelton 2018]; Bazoukis 2018).
Tablet: Oral: Initial: 25 mg once daily; titrate as needed after ~2 to 4 weeks based on response and tolerability up to 100 mg once daily (ACC/AHA [Whelton 2018]; Bazoukis 2018; Oxlund 2013; Williams 2015). Some experts recommend a starting dose of 12.5 mg once daily and generally do not exceed 50 mg once daily in the absence of primary aldosteronism (Brook 2020). Patients with severe asymptomatic hypertension and no signs of acute end organ damage should be evaluated for medication titration within 1 week (Mann 2021).
Suspension: Oral: Initial: 20 mg/day in 1 or 2 divided doses; titrate as needed after ~2 to 4 weeks based on response and tolerability up to 75 mg/day in 1 or 2 divided doses. Patients with severe asymptomatic hypertension and no signs of acute end organ damage should be evaluated for medication titration within 1 week (Mann 2021).
Primary aldosteronism:
Tablet: Oral: Initial: 12.5 to 25 mg once daily (ES [Funder 2016]); gradually titrate to the lowest effective dose; usual maximum dose: 400 mg/day (Young 2020). For surgical candidates, the last dose should be administered the day of surgery; discontinue spironolactone on postoperative day 1 (ES [Funder 2016]; Young 2020).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Use with caution; monitor potassium prior to initiating spironolactone and closely during therapy. In circumstances where treatment with spironolactone is considered necessary, interventions such as dietary counseling on a low potassium diet, loop diuretics, sodium bicarbonate to correct metabolic acidosis, and prescribing daily GI cation exchangers (eg, patiromer, zirconium cyclosilicate) have been utilized (Agarwal 2019; Bakris 2015; Spinowitz 2019).
Altered kidney function:
Tablet:
Ascites due to cirrhosis; hypertension; primary aldosteronism: There are no specific dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.
Heart failure:
eGFR >50 mL/minute/1.73 m2: No initial dosage adjustment necessary.
eGFR 30 to 50 mL/minute/1.73 m2: Initial: 12.5 mg once daily or every other day; may double the dose every 4 weeks if serum potassium remains <5 mEq/L and renal function is stable, up to a maximum target dose of 25 mg/day (ACCF/AHA [Yancy 2013]).
eGFR <30 mL/minute/1.73 m2: Use not recommended (ACCF/AHA [Yancy 2013]); heart failure clinical trials excluded patients with serum creatinine ≥2.5 mg/dL (Pitt 1999; Pitt 2014).
Suspension:
Ascites due to cirrhosis; hypertension: There are no dosage adjustments provided in the manufacturer's labeling.
Heart failure:
eGFR >50 mL/minute/1.73 m2: No initial dosage adjustment necessary.
eGFR 30 to 50 mL/minute/1.73 m2: Initial: 10 mg once daily.
eGFR <30 mL/minute/1.73 m2: Use not recommended (ACCF/AHA [Yancy 2013]); heart failure clinical trials excluded patients with serum creatinine ≥2.5 mg/dL (Pitt 1999; Pitt 2014).
Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzed (Georgianos 2016):
Tablet: Not routinely recommended, but 2 small trials have demonstrated the safety of spironolactone in patients with end-stage kidney disease receiving dialysis (Charytan 2019; Hammer 2019), with a suggested maximum of 25 mg once daily (Charytan 2019). Start at lowest initial dose (eg, 12.5 mg daily or every other day) and only utilize if benefits outweigh the risks, potassium is well-controlled, and patients can be monitored closely for hyperkalemia (expert opinion).
Peritoneal dialysis: Unlikely to be significantly dialyzed given high degree of protein binding (expert opinion):
Tablet: Not routinely recommended, but 2 small trials have demonstrated the safety of doses up to 25 mg once daily in patients receiving peritoneal dialysis (Gueiros 2019; Ito 2014). Start at lowest initial dose (eg, 12.5 mg daily or every other day) and only utilize if benefits outweigh the risks, potassium is well-controlled, and patients can be monitored closely for hyperkalemia (expert opinion).
There are no specific dosage adjustments provided in the manufacturer's labeling; initiate with low dose and titrate slowly (cirrhosis). Use with caution; minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Oral:
CaroSpir: 25 mg/5 mL (5 mL) [contains saccharin sodium]
CaroSpir: 25 mg/5 mL (118 mL, 473 mL) [contains saccharin sodium; banana flavor]
Tablet, Oral:
Aldactone: 25 mg
Aldactone: 50 mg, 100 mg [scored]
Generic: 25 mg, 50 mg, 100 mg
May be product dependent
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Aldactone: 25 mg, 100 mg
Generic: 25 mg, 100 mg
Oral: May be taken with or without food; however, consistent administration with or without food is preferred to minimize fluctuations in drug exposure.
Oral:
Tablet: Administer with or without food; however, administer consistently with respect to food.
Suspension: Shake well before administering dose. Administer with or without food; however, administer consistently with respect to food.
Hazardous agent (NIOSH 2016 [group 2]).
Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.
NIOSH recommends single gloving for administration of intact tablets or capsules. If manipulating tablets/capsules (eg, to prepare an oral suspension), NIOSH recommends double gloving, a protective gown, and preparation in a controlled device; if not prepared in a controlled device, respiratory and eye/face protection as well as ventilated engineering controls are recommended. NIOSH recommends double gloving, a protective gown, and (if there is a potential for vomit or spit up) eye/face protection for administration of an oral liquid/feeding tube administration (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).
Tablet: Store below 25°C (77°F).
Suspension: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Aldactone and similar generics: Management of edema and sodium retention associated with heart failure unresponsive to other therapies, cirrhosis of liver accompanied by edema and/or ascites, or nephrotic syndrome unresponsive to other therapies; increase survival and to reduce hospitalization for severe heart failure (New York Heart Association class III to IV) when used in addition to standard therapy; management of hypertension unresponsive to other therapies; treatment of hypokalemia unresponsive to other therapies; prophylaxis of hypokalemia in patients taking digitalis; diagnose primary hyperaldosteronism by therapeutic trial; short-term preoperative treatment of primary hyperaldosteronism; long-term maintenance therapy for patients with discrete aldosterone-producing adrenal adenomas who are judged to be poor operative risks or who decline surgery; and long-term maintenance therapy for bilateral micro- or macronodular adrenal hyperplasia (idiopathic hyperaldosteronism) (All indications: FDA approved in adults)
CaroSpir: Treatment of edema associated with cirrhosis of liver, increase survival and to reduce hospitalization for severe heart failure (New York Heart Association class III to IV) when used in addition to standard therapy, and management of hypertension unresponsive to other therapies (All indications: FDA approved in adults)
Aldactone may be confused with Aldactazide.
Beers Criteria: Diuretics (spironolactone) are identified in the Beers Criteria as potentially inappropriate medications to be used with caution in patients 65 years and older due to the potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium concentration closely when initiating or adjusting the dose in older adults (Beers Criteria [AGS 2019]).
Aldactone: Brand name for spironolactone [US, Canada, multiple international markets], but also the brand name for potassium canrenoate [Austria, Czech Republic, Germany, Hungary, Poland].
Aldactone [US, Canada, multiple international markets] may be confused with Aldomet brand name for methyldopa [multiple international markets].
Spironolactone may cause gynecomastia in patients of any age that may affect one or both breasts (typically both) (Ref). Gynecomastia is usually reversible following discontinuation of therapy (Ref). Eplerenone, which is associated with a lower risk of gynecomastia, may be considered if continued aldosterone antagonist therapy is required (Ref).
Mechanism: Dose- and time-related; due to decreased androgen production, inhibition of androgen receptor binding, displacement of estradiol from sex hormone-binding globulin and enhanced peripheral conversion of testosterone to estradiol (Ref).
Onset: Delayed; may occur after 1 to 2 months to over a year of therapy
Risk factors:
• Higher doses (eg, ≥150 mg/day) (Ref)
• Longer duration of therapy (Ref)
Spironolactone may cause reversible hyperkalemia, which may result in hospitalization and in some cases death (Ref).
Mechanism: Dose-related; related to the pharmacologic action. Competes with aldosterone for binding to the mineralocorticoid receptor, thereby inhibiting the exchange of sodium for potassium in the distal convoluted renal tubule and preventing potassium excretion.
Onset: Intermediate; usually occurs within 4 weeks of initiation or dose titration (Ref).
Risk factors:
• Older age (Ref)
• Kidney impairment (Ref)
• Excessive potassium intake (eg, potassium supplements, potassium-containing salt substitutes)
• Concomitant use of certain drugs (eg, angiotensin-converting enzyme [ACE] inhibitors, angiotensin-receptor blockers, drospirenone, nonsteroidal anti-inflammatory drugs) (Ref). Concurrent use of larger doses of ACE inhibitors (eg, lisinopril ≥10 mg daily in adults) also increases risk (Ref).
• Heart failure (especially patients receiving higher doses and patients with diabetes mellitus, higher baseline serum potassium levels, and worse New York Heart Association functional class) (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%: Endocrine & metabolic: Gynecomastia (9%; up to 52% in patients receiving high doses [eg, ≥150 mg/day]) (Haynes 2009; Jeunemaitre 1987; Nuttall 2015; Prisant 2005)
Frequency not defined:
Cardiovascular: Vasculitis
Dermatologic: Chloasma, erythematous maculopapular rash, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
Endocrine & metabolic: Amenorrhea (Levitt 1970), decreased libido, hyperglycemia, hypocalcemia, hypomagnesemia, hyponatremia, hypovolemia
Gastrointestinal: Abdominal cramps, diarrhea, gastritis, gastrointestinal hemorrhage, gastrointestinal ulcer, nausea, vomiting
Genitourinary: Erectile dysfunction, irregular menses, mastalgia, postmenopausal bleeding
Hematologic & oncologic: Agranulocytosis (Whitling 1997), leukopenia, thrombocytopenia
Hepatic: Hepatotoxicity
Hypersensitivity: Anaphylaxis
Immunologic: Drug reaction with eosinophilia and systemic symptoms
Nervous system: Ataxia, confusion, dizziness, drowsiness, headache, lethargy, nipple pain
Neuromuscular & skeletal: Lower limb cramp
Renal: Renal failure syndrome, renal insufficiency
Miscellaneous: Fever
Postmarketing: Endocrine & metabolic: Gout (Ben Salem 2017), hyperkalemia (common: ≥10%) (Huang 2005; Shah 2005), hyperuricemia (Ben Salem 2017), metabolic acidosis (in patients with cirrhosis) (Feinfeld 1978; Gabow 1979), ovarian cyst (in a premature neonate) (Vachharajani 2001)
Hyperkalemia; Addison disease; concomitant use with eplerenone.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to spironolactone or any component of the formulation; acute renal insufficiency; severe renal impairment (eGFR <30 mL/minute/1.73 m2); anuria; concomitant use with heparin or low molecular weight heparin; pregnancy; breastfeeding.
Concerns related to adverse effects:
• Fluid/electrolyte imbalance: Fluid and electrolyte imbalance (eg, hypomagnesemia, hyponatremia, hypocalcemia, hyperglycemia, hyperkalemia) may occur. Patients with heart failure, renal disease, or cirrhosis may be particularly susceptible. Monitor and correct electrolyte disturbances; adjust dose to avoid dehydration.
• Tumorigenic: Shown to be a tumorigen in chronic toxicity animal studies. Recent retrospective and observational studies do not suggest an increased risk of prostate or breast cancer (McKenzie 2016; Rozner 2020; Sabatier 2019).
Disease-related concerns:
• Adrenal vein catheterization: Discontinue use prior to adrenal vein catheterization.
• 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. American College of Cardiology/American Heart Association 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 triple therapy with the combined use of an ACE inhibitor, ARB, and spironolactone. Therapy may need to be modified during an episode of diarrhea or dehydration or when loop diuretic therapy is interrupted (ACCF/AHA [Yancy 2013]).
Special populations:
• Elderly: Avoid use of tablets >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 [ACCF/AHA (Yancy 2013)]).
Other warnings/precautions:
• Suspension: Suspension is NOT therapeutically equivalent to tablets. In patients requiring >100 mg/dose, use tablets (>100 mg/dose of suspension may result in spironolactone concentration higher than expected).
None known.
Abiraterone Acetate: Spironolactone may diminish the therapeutic effect of Abiraterone Acetate. Risk C: Monitor therapy
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Alpha-/Beta-Agonists: Spironolactone may diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
AMILoride: May enhance the hyperkalemic effect of Spironolactone. Risk X: Avoid combination
Ammonium Chloride: Potassium-Sparing Diuretics may enhance the adverse/toxic effect of Ammonium Chloride. Specifically the risk of systemic acidosis. Risk C: Monitor therapy
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Angiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Angiotensin-Converting Enzyme Inhibitors: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Aspirin: May diminish the therapeutic effect of Spironolactone. Risk C: 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. Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
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. Risk C: Monitor therapy
Ciprofloxacin (Systemic): Spironolactone may enhance the arrhythmogenic effect of Ciprofloxacin (Systemic). Risk C: Monitor therapy
Cosyntropin: Spironolactone may diminish the diagnostic effect of Cosyntropin. Management: Patients receiving spironolactone should omit their pre-test dose on the day selected for cosyntropin testing. Risk D: Consider therapy modification
CycloSPORINE (Systemic): Potassium-Sparing Diuretics may enhance the hyperkalemic effect of CycloSPORINE (Systemic). Risk X: Avoid combination
CYP2C8 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Spironolactone may increase the serum concentration of CYP2C8 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Spironolactone may increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Diacerein: May enhance the therapeutic effect of Diuretics. Specifically, the risk for dehydration or hypokalemia may be increased. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: 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. Risk C: Monitor therapy
Drospirenone-Containing Products: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: 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. Potassium supplements may be needed to treat/prevent hypokalemia in selected patients with heart failure receiving eplerenone and high dose loop diuretics. Risk D: Consider therapy modification
Finerenone: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of Finerenone. Risk C: Monitor therapy
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. Risk C: Monitor therapy
Heparins (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. Risk C: Monitor therapy
Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: 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. Risk D: Consider therapy modification
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: 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. Risk C: 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. Risk D: Consider therapy modification
Opioid Agonists: May enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: Avoid coadministration of a potassium-sparing diuretic and a potassium salt. This combination should only be used in cases of significant hypokalemia, and only if serum potassium can be closely monitored. Risk D: Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
QuiNIDine: Potassium-Sparing Diuretics may diminish the therapeutic effect of QuiNIDine. Risk C: 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. Risk D: Consider therapy modification
Tacrolimus (Systemic): Potassium-Sparing Diuretics may enhance the hyperkalemic effect of Tacrolimus (Systemic). Risk C: Monitor therapy
Tolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Triamterene: May enhance the hyperkalemic effect of Spironolactone. Risk X: Avoid combination
Trimethoprim: May enhance the hyperkalemic effect of Spironolactone. Risk C: Monitor therapy
Food increases the bioavailability of unmetabolized spironolactone by ~90% to 95%.
Administration with food increases the bioavailability of spironolactone. Excessive potassium intake (eg, salt substitutes, low-salt foods, bananas, nuts) should be avoided.
Use of spironolactone is associated with menstrual irregularities (dose dependent); contraception is recommended when used in premenopausal women for the treatment of conditions such as hirsutism and acne (AAD [Zaenglein 2016]; Endocrine Society [Martin 2018]).
Women who require use of spironolactone for the treatment of primary hyperaldosteronism should use the lowest effective dose prior to a planned pregnancy, then stop treatment once the pregnancy is confirmed (Riester 2015).
Spironolactone crosses the placenta (Regitz-Zagrosek [ESC 2018]).
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to spironolactone may cause feminization of a male fetus (limited human data; Liszewski 2019).
Chronic maternal hypertension is associated with adverse events in the fetus/infant. The risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death may be increased with chronic hypertension in pregnancy. Actual risks may be related to duration and severity of maternal hypertension. The use of mineralocorticoid receptor antagonists for the treatment of hypertension in pregnancy is generally not recommended (ACOG 203 2019).
The treatment of edema associated with chronic heart failure during pregnancy is similar to that of nonpregnant patients. However, the use of mineralocorticoid receptor antagonists is not recommended. Patients diagnosed after delivery can be treated according to heart failure guidelines (ESC [Bauersachs 2016]; ESC [Regitz-Zagrosek 2018]).
Information related to the use of mineralocorticoid receptor antagonists for the treatment of primary hyperaldosteronism in pregnancy is limited. Women who require use of spironolactone for the treatment of primary hyperaldosteronism should stop treatment during the first trimester once the pregnancy is confirmed. Use of a mineralocorticoid receptor antagonist can be considered again in the second and third trimesters if necessary; high doses have been associated with intrauterine growth restriction (monitor) (Riester 2015).
Blood pressure, serum potassium, sodium, calcium (neonates) and renal function (baseline, periodically during therapy), fluid balance, bodyweight (daily: neonates, infants)
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
Note: Suspension results in 15% to 37% higher serum concentration compared to the tablet; doses of suspension >100 mg may result in higher spironolactone concentrations than expected.
Duration: Tablet: 2 to 3 days
Bioavailability: High-fat/-calorie meal increased the bioavailability of spironolactone ~90%.
Protein binding: >90%
Metabolism: Rapid and extensive; hepatic to multiple metabolites, including active metabolites canrenone, 7-alpha-spirolactone, and 6-beta-hydroxy-7-alpha
Half-life elimination:
Tablet: Spironolactone: 1.4 hours; Canrenone: 16.5 hours (terminal); 7-alpha-spirolactone: 13.8 hours (terminal)
Suspension: Spironolactone: 1 to 2 hours; Canrenone, 7-alpha-spirolactone, and 6-beta-hydroxy-7-alpha: 10 to 35 hours.
Time to peak, serum:
Tablet: 2.6 to 4.3 hours (primarily as active metabolites)
Suspension: Spironolactone: 0.5 to 1.5 hours; Canrenone: 2.5 to 5 hours
Excretion: Urine (primarily as metabolites) and bile (secondary)
Hepatic function impairment: Terminal half-life is increased in patients with cirrhotic ascites.
5 mg/mL Oral Suspension (ASHP Standard Concentration) (ASHP 2017)
A 5 mg/mL oral suspension may be made with tablets. Crush twelve 50 mg tablets in a mortar and reduce to a fine powder. Add small portions of distilled water and mix to a uniform paste; mix while adding cherry syrup to almost 120 mL; transfer to a calibrated glass bottle, rinse mortar with cherry syrup, and add quantity of cherry syrup sufficient to make 120 mL. Label "shake well" and "refrigerate." Stable for 28 days at room temperature or refrigerated (Mathur 1989).
1 mg/mL Oral Suspension
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).
25 mg/mL Oral Suspension
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).
Suspension (CaroSpir Oral)
25 mg/5 mL (per mL): $3.88
Tablets (Aldactone Oral)
25 mg (per each): $3.19
50 mg (per each): $5.60
100 mg (per each): $9.38
Tablets (Spironolactone Oral)
25 mg (per each): $0.19 - $0.46
50 mg (per each): $0.81 - $0.88
100 mg (per each): $1.42
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