Eplerenone 50 mg Tablet, Film Coated, 30-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Aldosterone Antagonist class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Eplerenone is used to treat high blood pressure. It is also used after a heart attack to improve recovery. Eplerenone is in a class of medications called mineralocorticoid receptor antagonists. It works by blocking the action of aldosterone, a natural substance in the body that raises blood pressure.
Read the full MedlinePlus article ↗- That depends on why your doctor prescribed it. If you have high blood pressure, eplerenone helps lower it — which reduces your risk of stroke and heart attack over time. If you rec...
- What exactly is eplerenone supposed to do for me?
- Nope — food doesn't affect how well eplerenone is absorbed, so you can take it with a meal or on an empty stomach, whichever is easier for you. The most important thing is to take...
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Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Eplerenone — tap one for details:
Eplerenone may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII M28OL1HH48
Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
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Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
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Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
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UNII 0VUT3PMY82
Hypromellose 2910 is a plant-derived thickening agent made from cellulose. In medicines, it forms protective coatings on tablets or capsules, controls how fast the drug releases, and thickens liquid formulations.
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Hypromellose 2910 is a plant-based cellulose derivative that acts as a thickener, binder, and film-coating agent. It helps control how quickly the medicine dissolves and protects the tablet or capsule from moisture and light.
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UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII B697894SGQ
Polyethylene glycol 400 is a clear, thick liquid made from petroleum-derived polymers. It acts as a solvent and humectant in medicines, helping dissolve active ingredients and retain moisture in the formulation.
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Polysorbate 80 is a synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together in medications and improves how the product disperses in the body.
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UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
12 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $0.466 | $13.98 / 30 tablets |
| Medicaid paysCMS SDUD · 12 mo | $0.6515 | $19.55 / 30 tablets |
| Medicare drug plans payPart D · Q2 2026 | $0.8345 | $25.04 / 30 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Eplerenone 50 mg 16571-0174-03 | Rising | 30 tablets | $0.466 | AB | Availability likely | — |
| Eplerenone 50 mgthis 16729-0294-10 | Accord | 30 tablets | $0.466 | AB | Availability likely | — |
| Eplerenone 50 mg 31722-0050-30 | Camber | 30 tablets | $0.466 | AB | Availability likely | — |
| Eplerenone 50 mg 59762-1108-01 | Mylan | 30 tablets | $0.466 | AB | Availability likely | — |
| Eplerenone 50 mg 59762-1720-01 | Mylan | 30 tablets | $0.466 | AB | Discontinued | — |
| Eplerenone 50 mg 69367-0308-09 | Westminster | 90 tablets | $0.466 | AB | Availability likely | — |
| Eplerenone 50 mg 42291-0455-30 | AvKARE | 30 tablets | — | AB | Discontinued | — |
| Eplerenone 50 mg 51991-0878-11 | Breckenridge | 10 tablets | — | AB | FDA listed | — |
| Inspra 50 mg 58151-0143-93 | Viatris | 30 tablets | — | AB | FDA listed | — |
| Eplerenone 50 mg 71205-0864-00 | Proficient | 100 tablets | — | AB | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 16729-0294-10 You're viewing this | 30 TABLET, FILM COATED in 1 BOTTLE (16729-294-10) | $0.4659 / ea | $13.98 | 2018-10-09 | Active |
| 16729-0294-15 | 90 TABLET, FILM COATED in 1 BOTTLE (16729-294-15) | $0.4659 / ea | $41.93 | 2018-10-09 | Active |
You're viewing the smallest of 2 pack sizes for this product.
This pack has the lowest per-ea cost of the 2 priced pack sizes ($0.4659 NADAC).
In Medicaid, this is the most-dispensed pack of this product — about 86% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in NDC 16729-0294-10?
What is the difference between NDC 16729-0294-10 and NDC 16729-0294-15?
What NDC number is used to bill for this package of Eplerenone 50 mg Tablet, Film Coated?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Eplerenone is an aldosterone antagonist indicated for: Improving survival of stable adult patients with symptomatic heart failure with reduced ejection fraction (HFrEF) after an acute myocardial infarction. (1.1) The treatment of hypertension in adults, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. ( 1.2 )
1.1Heart Failure Post-Myocardial Infarction Eplerenone is indicated to improve survival of stable adult patients with symptomatic heart failure with reduced ejection fraction (≤40%) (HFrEF) after an acute myocardial infarction (MI).
1.2Hypertension Eplerenone tablets are indicated for the treatment of hypertension in adults, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular (CV) events, primarily strokes and MI. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes.
Control of high blood pressure should be part of comprehensive CV risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).Control of high blood pressure should be part of comprehensive CV risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake.
Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce CV morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits.
The largest and most consistent CV outcome benefit has been a reduction in the risk of stroke, but reductions in MI and CV mortality also have been seen regularly.Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce CV morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits.
The largest and most consistent CV outcome benefit has been a reduction in the risk of stroke, but reductions in MI and CV mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased CV risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.Elevated systolic or diastolic pressure causes increased CV risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hyp…
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION HFrEF Post-MI: Initiate treatment with 25 mg once daily. Titrate to maximum of 50 mg once daily within 4 weeks, as tolerated. Dose adjustments may be required based on potassium levels.
( 2.1 ) Hypertension : 50 mg once daily,alone or combined with other antihypertensive agents. For inadequate response, increase to 50 mg twice daily. Higher dosages are not recommended.
( 2.2 ) For all patients: Measure serum potassium before starting eplerenone tablets and periodically thereafter. ( 2.3 )
2.1Heart Failure Post-Myocardial Infarction Initiate treatment at 25 mg once daily and titrate to the recommended dose of 50 mg once daily, preferably within 4 weeks as tolerated by the patient. Once treatment with eplerenone has begun, adjust the dose based on the serum potassium level as shown in Table 1. Table 1.
Dose Adjustment in Heart Failure Post-MI Serum Potassium (mEq/L) Dose Adjustment <5.0 25 mg every other day to 25 mg once daily 25 mg once daily to 50 mg once daily 5.0 to
5.4No adjustment 5.5 to 5.9 50 mg once daily to 25 mg once daily 25 mg once daily to 25 mg every other day 25 mg every other day to withhold ≥6.0 Withhold and restart at 25 mg every other day when potassium levels fall to <5.5 mEq/L
2.2Hypertension The recommended starting dose of eplerenone tablets are 50 mg administered once daily. The full therapeutic effect of eplerenone tablet is apparent within 4 weeks. For patients with an inadequate blood pressure response to 50 mg once daily increase the dosage of eplerenone tablets to 50 mg twice daily.
Higher dosages of eplerenone tablets are not recommended because they have no greater effect on blood pressure than 100 mg and are associated with an increased risk of hyperkalemia. [see Clinical Studies (14.2) ].
2.3Recommended Monitoring Measure serum potassium before initiating eplerenone tablets therapy, within the first week, and at one month after the start of treatment or dose adjustment. Assess serum potassium periodically thereafter. Check serum potassium and serum creatinine within 3 to 7 days of a patient initiating a moderate CYP3A inhibitor ACE inhibitors, angiotensin II blockers or nonsteroidal anti-inflammatories.
2.4Dose Modification for Use with Moderate CYP3A Inhibitors In post-MI HFrEF patients receiving a moderate CYP3A inhibitor (e.g., erythromycin, saquinavir, verapamil, and fluconazole), do not exceed 25 mg once daily. In patients with hypertension receiving a moderate CYP3A inhibitor, initiate at 25 mg once daily. For inadequate blood pressure response, dosing may be increased to a maximum of 25 mg twice daily. [see Drug Interactions (7.1) ].
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS 25 mg tablets: yellow diamond shape biconvex film-coated tablets, debossed with "E1" on one side and plain on the other side. 50 mg tablets: yellow diamond shape biconvex film-coated tablets, debossed with "E2" on one side and plain on the other side. Tablets: 25 mg, 50 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS For all patients: Serum potassium >5.5 mEq/L at initiation ( 4 ) Creatinine clearance ≤30 mL/min ( 4 ) Concomitant use with strong CYP3A inhibitors ( 4 , 7.1 ) For the treatment of hypertension: Type 2 diabetes with microalbuminuria ( 4 ) Serum creatinine >2.0 mg/dL in males, >1.8 mg/dL in females ( 4 ) Creatinine clearance <50 mL/min ( 4 ) Concomitant use of potassium supplements or potassium-sparing diuretics ( 4 ) For All Patients Eplerenone tablets are contraindicated in all patients with: serum potassium >5.5 mEq/L at initiation, creatinine clearance ≤30 mL/min, or concomitant administration of strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, and nelfinavir). [see Drug Interactions (7.1) , Clinical Pharmacology (12.3) ].
For Patients Treated for Hypertension Eplerenone tablets are contraindicated for the treatment of hypertension in patients with: type 2 diabetes with microalbuminuria, serum creatinine >2.0 mg/dL in males or >1.8 mg/dL in females, creatinine clearance <50 mL/min, or concomitant administration of potassium supplements or potassium-sparing diuretics (e.g., amiloride, spironolactone, or triamterene). [see Warnings and Precautions (5.1) , Adverse Reactions (6.2) , Drug Interactions (7) , and Clinical Pharmacology (12.3) ].
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Hyperkalemia: Patients with decreased renal function diabetes, proteinuria or patients who are taking ACEs and ARBs, NSAIDs or moderate CYP3A inhibitors are at increased risk. Monitor serum potassium levels and adjust dose as needed. ( 5.1 )
5.1Hyperkalemia The risk of hyperkalemia is higher in patients with impaired renal function, proteinuria , diabetes and those concomitantly treated with ACEs, ARBs, NSAIDs and moderate CYP3A inhibitors. Minimize the risk of hyperkalemia with proper patient selection and monitoring [see Dosage and Administration (2.1) , Contraindications (4) , Adverse Reactions (6.2) , and Drug Interactions (7) ] . Monitor patients for the development of hyperkalemia until the effect of eplerenone is established.
Patients who develop hyperkalemia (5.5 to 5.9 mEq/L) may continue eplerenone therapy with proper dose adjustment. Dose reduction decreases potassium levels. Patients on moderate CYP3A inhibitors that cannot be avoided should have their dose of eplerenone reduced [see Drug Interactions (7.2) ].
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Hyperkalemia [see Warnings and Precautions (5.1) ] HFrEF Post-MI: Most common adverse reactions (>2% and more frequent than with placebo): hyperkalemia and increased creatinine. (6.1) Hypertension : In clinical studies, adverse reactions with eplerenone were uncommon. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Accord Healthcare Inc at 1-866-941-7875 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice. Heart Failure Post-Myocardial Infarction In EPHESUS, safety was evaluated in 3307 patients treated with eplerenone and 3301 placebo-treated patients. The overall incidence of adverse events reported with eplerenone (78.9%) was similar to placebo (79.5%).
Adverse events occurred at a similar rate regardless of age, gender, or race. Patients discontinued treatment due to an adverse event at similar rates in either treatment group (4.4% eplerenone vs. 4.3% placebo), with the most common reasons for discontinuation being hyperkalemia, MI, and abnormal renal function.
Adverse reactions that occurred more frequently in patients treated with eplerenone than placebo were hyperkalemia (3.4% vs. 2.0%) and increased creatinine (2.4% vs. 1.5%).
Discontinuations due to hyperkalemia or abnormal renal function were less than 1.0% in both groups. Hypertension Eplerenone has been evaluated for safety in 3,091 patients treated for hypertension. A total of 690 patients were treated for over 6 months and 106 patients were treated for over 1 year.
In placebo-controlled studies, the overall rates of adverse events were 47% with eplerenone and 45% with placebo. Adverse events occurred at a similar rate regardless of age, gender, or race. Therapy was discontinued due to an adverse event in 3% of patients treated with eplerenone and 3% of patients given placebo.
The most common reasons for discontinuation of eplerenone were headache, dizziness, angina pectoris/MI, and increased GGT. Gynecomastia and abnormal vaginal bleeding were reported with eplerenone but not with placebo. The rates increased with increasing duration of therapy.
6.2Postmarketing Experience The following adverse reactions have been identified during postapproval use of eplerenone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Skin: angioedema, rash
6.3Clinical Laboratory Test Findings Heart Failure Post-Myocardial Infarction Creatinine: Increases of more than 0.5 mg/dL were reported for 6.5% of patients administered eplerenone and for 4.9% of placebo-treated patients. Potassium: In EPHESUS [see Clinical Studies (14.1)] , the frequencies of patients with changes in potassium (<3.5 mEq/L or >5.5 mEq/L or ≥6.0 mEq/L) receiving eplerenone compared with placebo are displayed in Table 2. Table 2.
Hypokalemia (<3.5 mEq/L) or Hyperkalemia (>5.5 or ≥6.0 mEq/L) in EPHESUS Potassium (mEq/L) Eplerenone (N=3251) n(%) Placebo (N=3237) n(%) <3.5 273 (8.4) 424 (13.1) >5.5 508 (15.6) 363 (11.2) ≥6.0 180 (5.5) 126 (3.9) Rates of hyperkalemia increased with decreasing renal function. Table 3. Rates of Hyperkalemia (>5.5 mEq/L) in EPHESUS by Baseline Creatinine Clearance * * Estimated using the Cockroft-Gault formula.
Baseline Creatinine Clearance Eplerenone (N=508) n(%) Placebo (N=363) n(%) ≤30 mL/min 160 (32) 82 (23) 31 to 50 mL/min 122 (24) 46 (13) 51 to 70 mL/min 86 (17) 48 (13) >70 mL/min 56 (11) 32 (9) The rates of hyperkalemia in EPHESUS in the eplerenone-treated group vs. placebo were increased in patients with proteinuria (16% vs…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS CYP3A Inhibitors: In post-MI HFrEF patients, do not exceed 25 mg once daily when used with moderate CYP3A inhibitors (e.g., verapamil, erythromycin, saquinavir, fluconazole). In patients with hypertension, initiate at 25 mg once daily. For inadequate blood pressure response, dosing may be increased to a maximum of 25 mg twice daily. ( 2.4 , 7.1 , 12.3 )
7.1CYP3A Inhibitors Eplerenone metabolism is predominantly mediated via CYP3A. Do not use eplerenone with drugs that are strong inhibitors of CYP3A. [see Contraindications (4) and Clinical Pharmacology (12.3) ]. In post-MI HFrEF patients taking a moderate CYP3A inhibitor, do not exceed 25 mg once daily.
In patients with hypertension taking a moderate CYP3A inhibitor, initiate at 25 mg once daily. For inadequate blood pressure response, dosing may be increased to a maximum of 25 mg twice daily [see Dosage and Administration (2.3, 2.4) and Clinical Pharmacology (12.3) ].
7.2ACE Inhibitors and Angiotensin II Receptor Antagonists The risk of hyperkalemia increases when eplerenone is used in combination with an ACE inhibitor and/or an ARB. A close monitoring of serum potassium and renal function is recommended, especially in patients at risk for impaired renal function, e.g., the elderly [see Warnings and Precautions (5.1) ].
7.3Lithium A drug interaction study of eplerenone with lithium has not been conducted. Lithium toxicity has been reported in patients receiving lithium concomitantly with diuretics and ACE inhibitors. Serum lithium levels should be monitored frequently if eplerenone is administered concomitantly with lithium.
7.4Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) A drug interaction study of eplerenone with an NSAID has not been conducted. The administration of other potassium-sparing antihypertensives with NSAIDs has been shown to reduce the antihypertensive effect in some patients and result in severe hyperkalemia in patients with impaired renal function. Therefore, when eplerenone and NSAIDs are used concomitantly, monitor blood pressure and serum potassium levels.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary The available data from published case reports on eplerenone use during pregnancy are insufficient to establish a drug-associated risk of major birth defects, miscarriage, adverse maternal or fetal outcomes (see Clinical Considerations). In animal studies, no adverse developmental effects were observed when eplerenone was administered to pregnant rats and rabbits during organogenesis at exposures 32 and 31 times, respectively the human exposure at the 100 mg/day therapeutic dose. The estimated background risk of major birth defects and miscarriage for the indicated population are unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death.
Pregnant women with hypertension should be carefully monitored and managed accordingly. Pregnant women with heart failure are at increased risk for preterm birth. Stroke volume and heart rate increase during pregnancy, increasing cardiac output, especially during the first trimester.
Clinical classification of heart disease may worsen with pregnancy and lead to maternal death. Closely monitor pregnant patients for destabilization of their heart failure. Data Animal Data Embryo-fetal development studies were conducted with doses up to 1000 mg/kg/day in rats and 300 mg/kg/day in rabbits (exposures up to 32 and 31 times the human AUC for the 100 mg/day therapeutic dose, respectively) administered during organogenesis.
No teratogenic effects were seen in rats or rabbits, although decreased rat fetal weights were observed, and decreased body weight in maternal rabbits and increased rabbit fetal resorptions and post-implantation loss were observed at the highest administered dosages. In a pre-and postnatal development study, pregnant rats were administered eplerenone at doses up to 1000 mg/kg/day from Gestation Day 6 through Lactation Day 20. Decreased pup weights were observed beginning at birth at 1000 mg/kg/day.
8.2Lactation Risk Summary There are no human data available on whether eplerenone is present in human milk, or has effects on breastfed infants or on milk production. Eplerenone was present in the milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk.
8.3Females and Males of Reproductive Potential Infertility Based on animal data, use of eplerenone may compromise male fertility. In mature rats, male fertility was decreased with eplerenone exposure at 17 times the 100 mg/day human therapeutic dose. Reversibility of effects was not evaluated [see Nonclinical Toxicology (13.1) ].
8.4Pediatric Use The safety and effectiveness of eplerenone for treatment of hypertension have not been established in pediatric patients. In a 10-week study of 304 hypertensive pediatric patients ages 4 to 16 years treated with eplerenone up to 100 mg per day, doses that produced exposure similar to that in adults, eplerenone did not lower blood pressure effectively. In this study and in a 1-year pediatric safety study in 149 patients (age range 5 to 17 years), the incidence of reported adverse events was similar to that of adults.
Eplerenone was not studied for treatment of hypertension in pediatric patients younger than 4 years of age because the study in older pediatric patients did not demonstrate effectiveness. The safety and effectiveness of eplerenone have not been established in pediatric patients with heart failure.
8.5 Geriatric Use Heart Failure Post-Myocardial Infarction Of the tot…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary The available data from published case reports on eplerenone use during pregnancy are insufficient to establish a drug-associated risk of major birth defects, miscarriage, adverse maternal or fetal outcomes (see Clinical Considerations). In animal studies, no adverse developmental effects were observed when eplerenone was administered to pregnant rats and rabbits during organogenesis at exposures 32 and 31 times, respectively the human exposure at the 100 mg/day therapeutic dose. The estimated background risk of major birth defects and miscarriage for the indicated population are unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death.
Pregnant women with hypertension should be carefully monitored and managed accordingly. Pregnant women with heart failure are at increased risk for preterm birth. Stroke volume and heart rate increase during pregnancy, increasing cardiac output, especially during the first trimester.
Clinical classification of heart disease may worsen with pregnancy and lead to maternal death. Closely monitor pregnant patients for destabilization of their heart failure. Data Animal Data Embryo-fetal development studies were conducted with doses up to 1000 mg/kg/day in rats and 300 mg/kg/day in rabbits (exposures up to 32 and 31 times the human AUC for the 100 mg/day therapeutic dose, respectively) administered during organogenesis.
No teratogenic effects were seen in rats or rabbits, although decreased rat fetal weights were observed, and decreased body weight in maternal rabbits and increased rabbit fetal resorptions and post-implantation loss were observed at the highest administered dosages. In a pre-and postnatal development study, pregnant rats were administered eplerenone at doses up to 1000 mg/kg/day from Gestation Day 6 through Lactation Day 20. Decreased pup weights were observed beginning at birth at 1000 mg/kg/day.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of eplerenone for treatment of hypertension have not been established in pediatric patients. In a 10-week study of 304 hypertensive pediatric patients ages 4 to 16 years treated with eplerenone up to 100 mg per day, doses that produced exposure similar to that in adults, eplerenone did not lower blood pressure effectively. In this study and in a 1-year pediatric safety study in 149 patients (age range 5 to 17 years), the incidence of reported adverse events was similar to that of adults.
Eplerenone was not studied for treatment of hypertension in pediatric patients younger than 4 years of age because the study in older pediatric patients did not demonstrate effectiveness. The safety and effectiveness of eplerenone have not been established in pediatric patients with heart failure.
🧓 Geriatric Use ▾
8.5Geriatric Use Heart Failure Post-Myocardial Infarction Of the total number of patients in EPHESUS, 3340 (50%) were 65 and over, while 1326 (20%) were 75 and over. Patients greater than 75 years did not appear to benefit from the use of eplerenone [see Clinical Studies (14.1)] . No differences in overall incidence of adverse events were observed between elderly and younger patients.
However, due to age-related decreases in creatinine clearance, the incidence of laboratory-documented hyperkalemia was increased in patients 65 and older [see Warnings and Precautions (5.1)]. Hypertension Of the total number of subjects in clinical hypertension studies of eplerenone, 1,123 (23%) were 65 and over, while 212 (4%) were 75 and over. No overall differences in safety or effectiveness were observed between elderly subjects and younger subjects, however due to age-related decreases in creatine clearance, the risk of hyperkalemia may be increased [see Warnings and Precautions (5.1) ].
🆘 Overdosage ▾
10 OVERDOSAGE No cases of human overdosage with eplerenone have been reported. Lethality was not observed in mice, rats, or dogs after single oral doses that provided C max exposures at least 25 times higher than in humans receiving eplerenone 100 mg/day. Dogs showed emesis, salivation, and tremors at a C max 41 times the human therapeutic C max , progressing to sedation and convulsions at higher exposures.
The most likely manifestation of human overdosage would be anticipated to be hypotension or hyperkalemia. Eplerenone cannot be removed by hemodialysis. Eplerenone has been shown to bind extensively to charcoal.
If symptomatic hypotension should occur, supportive treatment should be instituted. If hyperkalemia develops, standard treatment should be initiated.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Eplerenone binds to the mineralocorticoid receptor and blocks the binding of aldosterone, a component of the renin-angiotensin-aldosterone-system (RAAS). Aldosterone synthesis, which occurs primarily in the adrenal gland, is modulated by multiple factors, including angiotensin II and non-RAAS mediators such as adrenocorticotropic hormone (ACTH) and potassium. Aldosterone binds to mineralocorticoid receptors in both epithelial (e.g., kidney) and nonepithelial (e.g., heart, blood vessels, and brain) tissues and increases blood pressure through induction of sodium reabsorption and possibly other mechanisms.
Eplerenone has been shown to produce sustained increases in plasma renin and serum aldosterone, consistent with inhibition of the negative regulatory feedback of aldosterone on renin secretion. The resulting increased plasma renin activity and aldosterone circulating levels do not overcome the effects of eplerenone. Eplerenone selectively binds to human mineralocorticoid receptors relative to its binding to recombinant human glucocorticoid, progesterone, and androgen receptors.
12.2Pharmacodynamics There was no significant change in average heart rate among patients treated with eplerenone in the combined clinical studies. No consistent effects of eplerenone on heart rate, QRS duration, or PR or QT interval were observed in 147 normal subjects evaluated for electrocardiographic changes during pharmacokinetic studies.
12.3Pharmacokinetics Eplerenone is cleared predominantly by cytochrome P450 (CYP) 3A4 metabolism, with an elimination half-life of 3 to 6 hours. Steady state is reached within 2 days. Absorption is not affected by food.
Inhibitors of CYP3A (e.g., ketoconazole, saquinavir) increase blood levels of eplerenone. Absorption and Distribution Mean peak plasma concentrations of eplerenone are reached approximately 1.5 to 2 hours following oral administration. Absorption is not affected by food.
The absolute bioavailability of eplerenone is 69% following administration of a 100 mg oral tablet. Both peak plasma levels (C max ) and area under the curve (AUC) are dose proportional for doses of 25 mg to 100 mg and less than proportional at doses above 100 mg. Upon repeat dosing, steady state levels are reached within 2 days.
The plasma protein binding of eplerenone is about 50% and it is primarily bound to alpha 1-acid glycoproteins. The apparent volume of distribution at steady state ranged from 42 to 90 L. Eplerenone does not preferentially bind to red blood cells.
Metabolism and Excretion Eplerenone metabolism is primarily mediated via CYP3A4. No active metabolites of eplerenone have been identified in human plasma. Less than 5% of an eplerenone dose is recovered as unchanged drug in the urine and feces.
Following a single oral dose of radiolabeled drug, approximately 32% of the dose was excreted in the feces and approximately 67% was excreted in the urine. The elimination half-life of eplerenone is approximately 3 to 6 hours. The apparent plasma clearance is approximately 10 L/hr.
Age, Gender, and Race The pharmacokinetics of eplerenone at a dose of 100 mg once daily has been investigated in the elderly (≥65 years), in males and females, and in Blacks. At steady state, elderly subjects had increases in C max (22%) and AUC (45%) compared with younger subjects (18 to 45 years). The pharmacokinetics of eplerenone did not differ significantly between males and females.
At steady state, C max was 19% lower and AUC was 26% lower in Blacks. [see Dosage and Administration (2.4) and Use in Specific Populations (8.5) ]. Renal Impairment The pharmacokinetics of eplerenone was evaluated in patients with varying degrees of renal impairment and in patients undergoing hemodialysis. Compared with control subjects, steady state AUC and C max were increased by 38% and 24%, respectively, in patients with severe renal impairment and were decreased by 26% and 3%, respectively, in patients und…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Eplerenone binds to the mineralocorticoid receptor and blocks the binding of aldosterone, a component of the renin-angiotensin-aldosterone-system (RAAS). Aldosterone synthesis, which occurs primarily in the adrenal gland, is modulated by multiple factors, including angiotensin II and non-RAAS mediators such as adrenocorticotropic hormone (ACTH) and potassium. Aldosterone binds to mineralocorticoid receptors in both epithelial (e.g., kidney) and nonepithelial (e.g., heart, blood vessels, and brain) tissues and increases blood pressure through induction of sodium reabsorption and possibly other mechanisms.
Eplerenone has been shown to produce sustained increases in plasma renin and serum aldosterone, consistent with inhibition of the negative regulatory feedback of aldosterone on renin secretion. The resulting increased plasma renin activity and aldosterone circulating levels do not overcome the effects of eplerenone. Eplerenone selectively binds to human mineralocorticoid receptors relative to its binding to recombinant human glucocorticoid, progesterone, and androgen receptors.
12.2Pharmacodynamics There was no significant change in average heart rate among patients treated with eplerenone in the combined clinical studies. No consistent effects of eplerenone on heart rate, QRS duration, or PR or QT interval were observed in 147 normal subjects evaluated for electrocardiographic changes during pharmacokinetic studies.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Eplerenone tablets, 25 mg, are yellow diamond shape biconvex film-coated tablets, debossed with “E1” on one side and plain on the other side. They are supplied as follows: NDC Number Size 16729-293-10 Bottle of 30 tablets with a child-resistant closure 16729-293-15 Bottle of 90 tablets with a child-resistant closure 16729-293-16 Bottle of 500 tablets 16729-293-17 Bottle of 1000 tablets 16729-293-82 Hospital Unit Dose Blister Packages of 100 (10 x 10 unit dose) Eplerenone tablets, 50 mg, are yellow diamond shape biconvex film-coated tablets, debossed with “E2” on one side and plain on the other side.
They are supplied as follows: NDC Number Size 16729-294-10 Bottle of 30 tablets with a child-resistant closure 16729-294-15 Bottle of 90 tablets with a child-resistant closure 16729-294-16 Bottle of 500 tablets 16729-294-17 Bottle of 1000 tablets 16729-294-82 Hospital Unit Dose Blister Packages of 100 (10 x 10 unit dose) Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature].
📦 Storage and Handling ▾
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature].
📋 Description ▾
11 DESCRIPTION Eplerenone tablet contains eplerenone, a blocker of aldosterone binding at the mineralocorticoid receptor. Eplerenone is chemically described as Pregn-4-ene-7,21-dicarboxylic acid, 9,11-epoxy-17-hydroxy-3-oxo-, γ-lactone, methyl ester, (7α,11α,17α)-. Its empirical formula is C 24 H 30 O 6 and it has a molecular weight of 414.50.
The structural formula of eplerenone is represented below: Eplerenone is an odorless, white to off-white crystalline powder. It is very slightly soluble in water, with its solubility essentially pH-independent. The octanol/water partition coefficient of eplerenone is approximately 7.1 at pH 7.0.
Eplerenone tablets for oral administration contains 25 mg or 50 mg of eplerenone and the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl methyl cellulose, purified talc, magnesium stearate, titanium dioxide, polyethylene glycol, polysorbate 80, iron oxide yellow and iron oxide red. Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise patients receiving eplerenone tablets: Not to use potassium supplements or salt substitutes containing potassium without consulting the prescribing physician. [see Warnings and Precautions (5.1) ]. To call their physician if they experience dizziness, diarrhea, vomiting, rapid or irregular heartbeat, lower extremity edema, or difficulty breathing. [see Warnings and Precautions (5.1) ].