- ACRONYMS AND DEFINITIONS
- AHA - American Heart Association
- EF - Ejection Fraction
- HCTZ - Hydrochlorothiazide
- PI - Manufacturer's Package Insert
Eplerenone (Inspra®)
Dosage form
Tablet
- 25 mg
- 50 mg
Dosing
Heart failure with reduced EF
- Starting: 25 mg once daily
- Target: 50 mg once daily
- Max: 50 mg once daily
- See dosing adjustments based on potassium
- See AHA dosing recommendations in heart failure for more
- May take without regard to food
Hypertension
- Starting: 50 mg once daily
- Maintenance: 50 mg once or twice daily
- Max: 50 mg twice daily
- May take without regard to food
With CYP3A4 moderate inhibitors
- Heart failure: do not exceed 25 mg once daily
- Hypertension: start with 25 mg once daily. May increase to a maximum of 25 mg twice a day.
- May take without regard to food
- Do not take eplerenone with CYP3A4 strong inhibitors
Generic / Price
- YES/$Other
- Full blood pressure effect is seen within 4 weeks
- The eplerenone PI recommends checking serum potassium before initiating eplerenone therapy, within the first week, and at one month after the start of treatment or dose adjustment. Assess serum potassium periodically thereafter.
Spironolactone (Aldactone®)
Dosage forms
Tablet
- 25 mg
- 50 mg
- 100 mg
Dosing
Hypertension
- Starting: 50 - 100 mg/day
- Maintenance: 50 - 100 mg/day
- May give in one or two divided doses
- Full blood pressure effect typically seen within 2 weeks
- Food may increase absorption. Manufacturer makes no specific recommendation.
Heart failure with reduced EF
- Starting: 25 mg once daily
- Maintenance: 25 - 50 mg once daily
- Max: 50 mg/day
- See AHA dosing recommendations in heart failure for more
- Food may increase absorption. Manufacturer makes no specific recommendation.
Cirrhosis
- Starting: 100 mg/day
- Maximum: 400 mg/day
- May give in one or two divided doses
- Combine with loop diuretic to prevent hyperkalemia
- See cirrhosis for more
- Food may increase absorption. Manufacturer makes no specific recommendation.
Acne in women (off-label)
- In studies, doses of 25 - 200 mg/day were used
- In general, doses of ≤ 100 mg/day are effective and carry a lower risk of side effects
- Potassium monitoring is not recommended in healthy young women
- See acne for more
- Food may increase absorption. Manufacturer makes no specific recommendation.
Generic / Price
- YES/$Spironolactone (Carospir®)
Dosage forms
Suspension
- 25 mg/5 ml
- Comes in 118 ml bottle
- Store at room temperature
Dosing
NOTE: Carospir is not therapeutically equivalent to Aldactone. Do not use Carospir for spironolactone doses > 100 mg/day.
Hypertension
- Dosing: 20 - 75 mg/day
- May give in one or two divided doses
- Titrate dose at 2 week intervals
- Take consistently either with or without food. High fat and high calorie meals increase absorption.
Heart failure with reduced EF
- Starting: 20 mg once daily if potassium ≤ 5 mEq/L and CrCl > 50 ml/min
- Maintenance: 10 - 37.5 mg once daily
- Max: 37.5 mg/day
- Patients who develop hyperkalemia on 20 mg once daily may have their dose reduced to 20 mg every other day
- CrCl 30 - 50 ml/min: Consider starting dose of 10 mg once daily
- Take consistently either with or without food. High fat and high calorie meals increase absorption.
Cirrhosis
- Starting: 75 mg/day
- Maximum: 100 mg/day
- May give in one or two divided doses
- If doses > 100 mg/day are required, do not use Carospir
- Take consistently either with or without food. High fat and high calorie meals increase absorption.
Generic / Price
- NO/$$$$- SPIRONOLACTONE + HCTZ
Aldactazide® (HCTZ + spironolactone)
Dosage forms
Tablet
- HCTZ - Spironolactone
- 25 mg - 25 mg
- 50 mg - 50 mg
Dosing
Hypertension
- Dosing: 25/25 mg - 100/100 mg/day
- May be given once daily or in divided doses
- Food may increase the absorption of spironolactone. Manufacturer makes no specific recommendation.
Edema
- Dosing: 25/25 mg - 200/200 mg/day
- May be given once daily or in divided doses
- Food may increase the absorption of spironolactone. Manufacturer makes no specific recommendation.
Generic / Price
- 25/25 mg dose - YES/$
- 50/50 mg dose - NO/$$$$
| Eplerenone dose adjustments in heart failure based on serum potassium | |
|---|---|
| Serum Potassium (mEq/L) | Dose Adjustment |
| < 5.0 |
|
| 5.0 - 5.4 |
|
| 5.5 - 5.9 |
|
| ≥ 6.0 |
|
- Kidney disease dosing
- Eplerenone (Inspra®)
- CrCl < 50 ml/min (patients treated for hypertension): DO NOT USE
- CrCl ≤ 30 ml/min (all patients): DO NOT USE
- Spironolactone (Aldactone®)
- Use with caution in kidney disease
- Manufacturer makes no specific dosage recommendations
- Liver disease dosing
- Eplerenone (Inspra®)
- Mild-to-moderate liver disease (Child-Pugh A and B) - no dose adjustment necessary
- Severe liver disease (Child-Pugh C) - has not been studied
- Spironolactone (Aldactone®)
- Spironolactone is used in cirrhosis
- See liver failure above
- DRUG INTERACTIONS
- NOTE: Drug interactions presented here are NOT all-inclusive. Other interactions may exist. The interactions presented here are meant to encompass commonly prescribed medications and/or interactions that are well-documented. Always consult your physician or pharmacist before taking medications concurrently. CLICK HERE for more information on drug interactions.
- Spironolactone and eplerenone
- Lithium - aldosterone antagonists may reduce the clearance of lithium. Aldosterone antagonists should not be taken with lithium if possible. Lithium levels should be monitored closely in patients taking aldosterone antagonists.
- Medications that can raise potassium levels - AA may raise potassium levels and cause hyperkalemia. When taken with other potassium-raising medications, the risk is increased. While it is often appropriate to combine AA with other potassium-raising drugs, patients and providers should be aware of the potential risks. See RAAS inhibitor-induced hyperkalemia for recommendations on addressing hyperkalemia in AA-treated patients.
- Examples of medications that may raise potassium levels include:
- ARBs (valsartan, olmesartan, etc.)
- ACE inhibitors
- Aliskiren (Tekturna®)
- Cyclosporine (Neoral®)
- ENaC inhibitors (triamterene, amiloride)
- Finerenone (Kerendia®)
- Heparin - heparin raises potassium secondarily by inhibiting aldosterone synthesis. LMWH does not appear to have the same effect. [5]
- Penicillin G potassium injection (1 million units contains 1.68mEq of potassium)
- Potassium supplements (K-Dur®, etc)
- Tacrolimus (Prograf®)
- Trimethoprim (part of Bactrim® and Septra®)
- Voclosporin (Lupkynis®)
- NSAIDS (Advil®, ibuprofen, naprosyn, etc.) - NSAIDS can block the therapeutic effect of aldosterone antagonists. Patients should monitor for decreased effectiveness of aldosterone antagonists when taking NSAIDS for extended periods.
- Salt substitutes (No Salt®, No-Salt®, etc.) - salt substitutes typically have a high amount of potassium (16.4 mEq per 1/4 teaspoon). Patients should be aware that this may contribute to elevated potassium levels seen with aldosterone antagonists.
- Eplerenone (Inspra®)
- CYP3A4 strong inhibitors - DO NOT COMBINE. Eplerenone is a CYP3A4 sensitive substrate.
- CYP3A4 moderate inhibitors - when eplerenone is taken with CYP3A4 moderate inhibitors, the following dosing is recommended:
- Post-MI heart failure: do not exceed 25 mg once daily
- Hypertension: starting dose should be 25 mg once daily. May increase to a maximum of 25 mg twice a day.
- Check serum potassium and serum creatinine within 3 – 7 days after starting concomitant therapy with a CYP3A4 moderate inhibitor
- NSAIDs - Check serum potassium and serum creatinine within 3 – 7 days after starting concomitant therapy with an NSAID
- Spironolactone (Aldactone®)
- CYP3A4 substrates - spironolactone is an irreversible inhibitor of CYP3A4 in vitro. Doses of CYP3A4 substrates may need to be adjusted when combining.
- CYP2C8 substrates - spironolactone is an irreversible inhibitor of CYP2C8 in vitro. Doses of CYP2C8 substrates may need to be adjusted when combining.
- Digoxin (Lanoxin®) - Spironolactone has been shown to increase blood levels of digoxin. Spironolactone has also been shown to interfere with many of the assays used to measure digoxin levels. In patients taking digoxin, measure serum digoxin levels before initiating spironolactone with an assay that does not interact with spironolactone. Reduce the digoxin dose by 15 - 30% or reduce dosing frequency when starting spironolactone. Monitor digoxin levels closely.
- Metabolism and clearance
- Eplerenone (Inspra®)
- CYP3A4 - sensitive substrate
- Spironolactone (Aldactone®)
- CYP3A4 - major substrate and inhibitor
- CYP2C8 - minor substrate and inhibitor
- P-glycoprotein - inducer
- PRICE ($) INFO
Pricing legend
- $ = 0 - $50
- $$ = $51 - $100
- $$$ = $101 - $150
- $$$$ = > $150
- Pricing based on one month of therapy at standard dosing in an adult
- Pricing based on information from GoodRX.com®
- Pricing may vary by region and availability
- BIBLIOGRAPHY
- 1 - Manufacturer's package insert
- 2 - PMID 11733620
- 3 - PMID 20216123
- 4 - PMID 16740618
- 5 - PMID 22560830 - Use and safety of unfractionated heparin for anticoagulation during maintenance hemodialysis, Am J Kidney Dis (2021)