Dosage guidance:
Dosage form information: 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, moderate to severe (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 (Ref).
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 (Ref).
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 (Ref). For small-volume ascites in patients who weigh ≤50 kg, some experts recommend a starting dose of 50 mg once daily (Ref).
Hair loss, female pattern (off-label use):
Note: For use as an adjunctive agent or as alternative monotherapy in patients who have inadequate response to or who cannot take preferred therapies (Ref).
Tablet: Oral: Initial: 50 mg/day in 1 or 2 divided doses; if tolerated after 2 to 4 weeks, increase to 100 mg/day in 1 or 2 divided doses. If insufficient response after 6 months, may further increase dose up to 200 mg/day in 1 or 2 divided doses; usual effective dose: 100 to 200 mg/day. Treatment for at least 6 to 12 months is recommended for clinical benefit (Ref).
Heart failure:
Note: When initiating therapy, verify the following: serum potassium <5 mEq/L and serum creatinine ≤2.5 mg/dL in men and ≤2 mg/dL in women or eGFR >30 mL/minute/1.73 m2 . If patient develops hyperkalemia or kidney function worsens, reduce the dose, change to every-other-day dosing, or discontinue therapy; assess for other causes of hyperkalemia before permanent discontinuation. If serum potassium cannot be maintained <5.5 mEq/L, discontinue therapy (Ref).
Heart failure with preserved ejection fraction (off-label use):
Note: For use in patients with symptomatic heart failure with preserved ejection fraction (HFpEF) (≥50%) who have an elevated serum natriuretic peptide level or have been hospitalized for heart failure in the last 12 months (Ref). Some experts are more conservative regarding serum potassium for patients with HFpEF. They recommend initiating therapy or uptitrating the dose only if serum potassium is ≤4.7 mEq/L and eGFR is ≥30 mL/minute/1.73 m2. They recommend dose reduction or discontinuation if serum potassium is >5 mEq/L (Ref).
Tablet: Oral: Initial: 12.5 mg once daily; may double the dose every 2 to 4 weeks if serum potassium and kidney function are stable, up to a maximum target dose of 50 mg/day in 1 or 2 divided doses (Ref).
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) (≤40%) as part of an optimal medical regimen for HFrEF (Ref).
Tablet: Oral: Initial: 12.5 to 25 mg once daily; may double the dose every 4 weeks if serum potassium and kidney function are stable, up to a maximum target dose of 50 mg/day in 1 to 2 divided doses (Ref).
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 and kidney function are stable (Ref).
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 (Ref).
Tablet: Oral: Initial: 12.5 to 25 mg once daily; may double the dose every 4 weeks if serum potassium and kidney function are stable, up to a maximum target dose of 50 mg/day in 1 to 2 divided doses (Ref).
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 and kidney function are stable (Ref).
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 (Ref).
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 (Ref).
Hormone therapy for transgender females, assigned male at birth (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) (Ref). Monitor serum potassium levels 1 month after initiation and following dosage adjustments thereafter (Ref).
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 (Ref).
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 (Ref). 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 (Ref). Patients with severe asymptomatic hypertension and no signs of acute end organ damage should be evaluated for medication titration within 1 week (Ref).
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 (Ref).
Primary aldosteronism:
Tablet: Oral: Initial: 12.5 to 25 mg once daily (Ref); gradually titrate to the lowest effective dose; usual maximum dose: 400 mg/day (Ref). For surgical candidates, the last dose should be administered the day of surgery; discontinue spironolactone on postoperative day 1 (Ref).
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 (Ref).
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 kidney function is stable, up to a maximum target dose of 25 mg/day (Ref).
eGFR <30 mL/minute/1.73 m2: Use not recommended (Ref); heart failure clinical trials excluded patients with serum creatinine ≥2.5 mg/dL (Ref).
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 (Ref); heart failure clinical trials excluded patients with serum creatinine ≥2.5 mg/dL (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzed (Ref):
Tablet: Not routinely recommended, but 2 small trials have demonstrated the safety of spironolactone in patients with end-stage kidney disease receiving dialysis (Ref), with a suggested maximum of 25 mg once daily (Ref). 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 (Ref).
Peritoneal dialysis: Unlikely to be significantly dialyzed given high degree of protein binding (Ref):
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 (Ref). 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 (Ref).
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.
Refer to adult dosing.
(For additional information see "Spironolactone: Pediatric drug information")
Dosage guidance:
Dosing: 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).
Dosage form information: 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.
Bronchopulmonary dysplasia (BPD): Limited data available; efficacy results variable. Note: 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 (Ref).
Infants: Oral: 1.5 mg/kg/dose every 12 hours (Ref).
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 not to exceed 400 mg/day (Ref).
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 not to exceed 100 mg/day (Ref).
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 (Ref).
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 kidney impairment (Ref).
There are no dosage adjustments provided in the manufacturer's labeling. Use with caution; minor alterations of fluid and electrolyte balance may precipitate hepatic encephalopathy and coma in patients with liver disease with cirrhosis and ascites.
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:
• Kidney impairment (Ref)
• Older age (Ref)
• Excessive potassium intake (eg, potassium supplements, potassium-containing salt substitutes)
• Concurrent use of other medications that increase serum potassium (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) (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]) (Ref)
Frequency not defined:
Cardiovascular: Vasculitis
Dermatologic: Chloasma, erythematous maculopapular rash, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
Endocrine & metabolic: Decreased libido, hyperglycemia, hypocalcemia, hypomagnesemia, hyponatremia, hypovolemia, irregular menses, postmenopausal bleeding
Gastrointestinal: Abdominal cramps, diarrhea, gastritis, gastrointestinal hemorrhage, gastrointestinal ulcer, nausea, vomiting
Genitourinary: Erectile dysfunction, mastalgia, nipple pain
Hematologic & oncologic: Leukopenia, thrombocytopenia
Hepatic: Hepatotoxicity
Hypersensitivity: Anaphylaxis, drug reaction with eosinophilia and systemic symptoms
Nervous system: Ataxia, confusion, dizziness, drowsiness, headache, lethargy
Neuromuscular & skeletal: Lower limb cramp
Renal: Kidney failure, kidney impairment
Miscellaneous: Fever
Postmarketing:
Endocrine & metabolic: Amenorrhea (Ref), hyperkalemia (Ref), hyperuricemia (Ref), metabolic acidosis (in patients with cirrhosis) (Ref)
Genitourinary: Ovarian cyst (in a premature neonate) (Ref)
Hematologic & oncologic: Agranulocytosis (Ref)
Neuromuscular & skeletal: Gout (Ref)
Hyperkalemia; Addison disease; concomitant use with eplerenone.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to spironolactone or any component of the formulation; acute kidney insufficiency; severe kidney 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, kidney 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. Discontinue therapy if serum potassium cannot be maintained <5.5 mEq/L or if kidney function worsens. Consider the entire medical regimen and other potential causes of hyperkalemia (AHA/ACC/HFSA [Heidenreich 2022]).
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).
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]
Generic: 25 mg/5 mL (118 mL, 473 mL)
Tablet, Oral:
Aldactone: 25 mg
Aldactone: 50 mg, 100 mg [scored]
Generic: 25 mg, 50 mg, 100 mg
Yes
Suspension (CaroSpir Oral)
25 mg/5 mL (per mL): $4.40
Suspension (Spironolactone Oral)
25 mg/5 mL (per mL): $3.80 - $4.18
Tablets (Aldactone Oral)
25 mg (per each): $3.25
50 mg (per each): $5.71
100 mg (per each): $9.57
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 - $1.43
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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:
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.
Oral:
Tablet: May be taken with or without food; however, consistent administration with or without food is preferred to minimize fluctuations in drug exposure.
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, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Ascites due to cirrhosis: Management of edema in cirrhosis of the liver unresponsive to fluid and sodium restriction.
Heart failure with reduced ejection fraction: To increase survival, manage edema, and reduce need for hospitalization in patients with heart failure with reduced ejection fraction and New York Heart Association class III to IV symptoms; usually administered in conjunction with other heart failure therapies.
Hypertension, chronic: Management of hypertension unresponsive to other therapies.
Primary hyperaldosteronism (tablet only): Short-term preoperative treatment of primary hyperaldosteronism; long-term maintenance therapy for patients with discrete aldosterone-producing adrenal adenomas who are not candidates for surgery; long-term maintenance therapy for bilateral micro- or macronodular adrenal hyperplasia (idiopathic hyperaldosteronism).
Acne vulgaris, females, moderate to severe; Hair loss, female pattern; Heart failure with preserved ejection fraction; Hirsutism, females; Hormone therapy for transgender females (assigned male at birth); Post myocardial infarction, complicated by reduced ejection fraction
Aldactone may be confused with Aldactazide.
Beers Criteria: Diuretics 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 2023]).
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].
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abiraterone Acetate: Spironolactone may diminish the therapeutic effect of Abiraterone Acetate. Management: Consider alternatives to the combined use of spironolactone and abiraterone. If combined, monitor the clinical response to abiraterone closely, looking specifically for signs of clinical failure and/or disease progression. Risk D: Consider therapy modification
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
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
Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Aspirin: May diminish the therapeutic effect of Spironolactone. 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
Finerenone: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of Finerenone. Risk C: Monitor therapy
Fludrocortisone: May diminish the therapeutic effect of Mineralocorticoid (Aldosterone) Receptor Antagonists. Mineralocorticoid (Aldosterone) Receptor Antagonists may diminish the therapeutic effect of Fludrocortisone. Risk C: Monitor therapy
Flunarizine: May enhance the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Heparin: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Heparins (Low Molecular Weight): May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. 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
Iloperidone: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Indoramin: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Isocarboxazid: May enhance the hypotensive effect of Diuretics. Risk X: Avoid combination
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy
Lithium: Potassium-Sparing Diuretics may increase the serum concentration of Lithium. Potassium-Sparing Diuretics may decrease the serum concentration of Lithium. Risk C: Monitor therapy
Loop Diuretics: May enhance the hypotensive effect of Antihypertensive Agents. 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 decrease the serum concentration of Mitotane. Risk X: Avoid combination
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
Polyethylene Glycol-Electrolyte Solution: Diuretics may enhance the nephrotoxic effect of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Spironolactone. Risk X: Avoid combination
Potassium-Sparing Diuretics: May enhance the hyperkalemic effect of other Potassium-Sparing Diuretics. Risk X: Avoid combination
Prazosin: Antihypertensive Agents may enhance the hypotensive effect of Prazosin. Risk C: Monitor therapy
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
Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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. Risk C: Monitor therapy
Tacrolimus (Systemic): Potassium-Sparing Diuretics may enhance the hyperkalemic effect of Tacrolimus (Systemic). Risk C: Monitor therapy
Terazosin: Antihypertensive Agents may enhance the hypotensive effect of Terazosin. Risk C: Monitor therapy
Tolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Trimethoprim: May enhance the hyperkalemic effect of Spironolactone. Risk C: Monitor therapy
Urapidil: Antihypertensive Agents may enhance the hypotensive effect of Urapidil. Risk C: Monitor therapy
Food increases the bioavailability of unmetabolized spironolactone by ~90% to 95%.
Spironolactone is associated with dose-dependent menstrual irregularities (AAD [Zaenglein 2016]; ES [Funder 2016]; ES [Martin 2018]; Kallistratos 2018). Some guidelines recommend use of combination oral contraception in premenopausal patients to regulate menses and prevent pregnancy (AAD [Zaenglein 2016], ES [Martin 2018]). Decreasing the dose or switching to an alternative mineralocorticoid receptor antagonist may be appropriate for some indications (ES [Funder 2016]; Kallistratos 2018).
Spironolactone is associated with dose-dependent erectile dysfunction (AAD [Zaenglein 2016]; ES [Funder 2016]; ES [Martin 2018]; Kallistratos 2018). Decreasing the dose or switching to an alternative mineralocorticoid receptor antagonist may be appropriate for some indications (ES [Funder 2016]; Kallistratos 2018). The antiandrogen blocking activity of spironolactone results in decreased spontaneous erections, sperm production, and testicular volume in transgender patients undergoing feminizing therapy (ES [Hembree 2017]).
Patients taking spironolactone for primary aldosteronism (PA) who are planning to become pregnant should be switched to other agents prior to conception when possible (Forestiero 2022). Patients who require use of spironolactone for the treatment of PA should use the lowest effective dose prior to a planned pregnancy, then stop treatment once their pregnancy is confirmed (Riester 2015).
Medications considered acceptable for the treatment of chronic hypertension during pregnancy may generally be continued in patients trying to conceive. The use of mineralocorticoid receptor antagonists is not recommended for the treatment of chronic hypertension in pregnant patients (ACOG 2019). Consider transitioning to an agent preferred for use during pregnancy in patients planning to become pregnant (ACC/AHA [Whelton 2018]; ACOG 2019; NICE 2019).
Patients with heart failure who are planning to become pregnant should discontinue mineralocorticoid receptor antagonists prior to conception (AHA/ACC/HFSA [Heidenreich 2022]).
Spironolactone crosses the placenta (ESC [Regitz-Zagrosek 2018]).
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to spironolactone during the period of embryogenesis may cause feminization of a male fetus (limited human data; Liszewski 2019). High doses late in pregnancy may be associated with intrauterine growth restriction (Riester 2015).
Chronic maternal hypertension is associated with adverse events in the fetus/infant. Chronic maternal hypertension may increase the risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to the duration and severity of maternal hypertension. Untreated chronic hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, preeclampsia, delivery complications, stroke, and myocardial infarction (ACOG 2019). Patients with preexisting hypertension may continue their medication during pregnancy unless contraindications exist (ESC [Regitz-Zagrosek 2018]). When treatment of chronic hypertension during pregnancy is indicated, the use of mineralocorticoid receptor antagonists is generally not recommended (ACOG 2019).
Data specific to the treatment of primary aldosteronism (PA) in pregnancy are limited. Patients with PA should stop spironolactone before conception or during the first trimester once the pregnancy is confirmed (Riester 2015). If spironolactone is stopped and PA is not controlled, agents other than spironolactone are recommended for the adjunctive treatment of PA during pregnancy (Forestiero 2022; Sanga 2022).
Heart failure in pregnancy is associated with adverse maternal and fetal outcomes, including premature birth, infants born small for gestational age, and increased risk of maternal and fetal death (Bright 2021). When treatment of heart failure during pregnancy is needed, the use of an agent other than a mineralocorticoid receptor antagonist is recommended (AHA/ACC/HFSA [Heidenreich 2022]; ESC [Regitz-Zagrosek 2018]).
Case reports describe the use of potassium-sparing diuretics such as spironolactone for the adjunctive treatment of Gitleman syndrome during pregnancy (Calò 2012; Moustakakis 2012; Shahzad 2019).
The active metabolite of spironolactone (canrenone) is present in breast milk.
Data are available from a case report following maternal use of spironolactone 25 mg twice daily throughout pregnancy, then 4 times daily after delivery. Milk and maternal serum samples were obtained 17 days after birth. Two hours after the maternal dose, canrenone concentrations were ~144 ng/mL (serum) and ~104 ng/mL (milk). When measured 14.5 hours after the dose, canrenone concentrations were ~92 ng/mL (serum) and ~47 ng/mL (milk). The authors calculated the estimated maximum amount of canrenone to the breastfeeding infant to be ~0.2% of the maternal dose of spironolactone (Phelps 1977).
Spironolactone is considered compatible with breastfeeding (WHO 2002). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Administration with food increases the bioavailability of spironolactone. Excessive potassium intake (eg, salt substitutes, low-salt foods, bananas, nuts) should be avoided.
BP, serum potassium within 1 week of initiation or dose titration, again 2 to 4 weeks later, and regularly thereafter, especially in patients taking other medications that can cause hyperkalemia (refer also to indication-specific potassium monitoring), other serum electrolytes (eg, sodium), uric acid, glucose, kidney function, volume status (Brook 2020; manufacturer's labeling).
Heart failure: Serum potassium and kidney 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 angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, a new cycle of monitoring should be done. If serum potassium increases to >5.5 mEq/L or kidney function worsens, hold doses until potassium is <5 mEq/L and consider restarting with a reduced dose after confirming resolution of hyperkalemia/kidney insufficiency for at least 72 hours. If serum potassium cannot be maintained <5.5 mEq/L, discontinue therapy (ACC [Maddox 2021]; AHA/ACC/HFSA [Heidenreich 2022]).
Transgender hormone therapy: Serum testosterone levels (goal: <50 ng/dL) every 3 months during the first year and then annually or biannually; serum potassium after the first month, then at least every 3 months (or after dose titrations following the first month); other serum electrolytes (eg, sodium) every 3 months for the first year then annually; routine cancer and laboratory screening as in non-transgender individuals for all tissues present (ES [Hembree 2017]; Tangpricha 2024).
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.
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