eplerenone

Eplerenone is a medication used to treat congestive heart failure in patients who have had a heart attack (myocardial infarction) and to lower blood pressure in patients with high blood pressure (hypertension). Eplerenone is a selective aldosterone antagonist that reduces blood pressure by blocking the activity of aldosterone, a mineralocorticoid hormone that regulates blood pressure.

Aldosterone increases blood pressure by increasing water and sodium retention in the body. The hormone binds to mineralocorticoid receptors located in the kidneys, brain, heart, and blood vessels inducing sodium and water absorption and excretion of potassium. Hypertension increases the risk for cardiovascular adverse events. In addition, aldosterone is implicated in the progression of scar tissue in the heart muscles (myocardial fibrosis), especially following myocardial infarction.

Eplerenone binds to the mineralocorticoid receptors and prevents aldosterone from stimulating them, reducing blood pressure and sodium/water retention. This helps reduce the risk of congestive failure, myocardial fibrosis, and vascular fibrosis, improving survival in patients who have had a myocardial infarction (MI).

The uses of eplerenone include:

FDA-approved

• Management of chronic hypertension
• Congestive heart failure (CHF) after an acute MI

Off-label

• Heart failure with a preserved ejection fraction
• Heart failure with a reduced ejection fraction
• Primary hyperaldosteronism

• Do not use eplerenone in patients with hypersensitivity to any of the components in the formulation.
• Do not use in patients with:
  • Serum potassium over 5.5 mEq/L at initiation
  • Creatinine clearance 30 mL/minute or lower
  • Concomitant administration of strong CYP3A inhibitors such as ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, and nelfinavir
• Do not use for the treatment of hypertension in patients with:
  • Type 2 diabetes with microalbuminuria
  • Serum creatinine above 2.0 mg/dL in males or above 1.8 mg/dL in females
  • Creatinine clearance below 50 mL/minute
  • Concomitant administration of potassium supplements or potassium-sparing diuretics including amiloride, spironolactone, or triamterene
• Use eplerenone with caution in patients with:
  • Impaired liver or kidney function
  • Metabolic or respiratory acidosis
  • Hypersensitivity to spironolactone
• Use with caution in patients with high blood potassium levels (hyperkalemia). The risk is higher in patients with:
  • Impaired kidney function
  • Protein in the urine (proteinuria)
  • Diabetes
  • Concomitant treatment with medications including ACEs, ARBs, NSAIDs, and moderate CYP3A inhibitors.
• Monitor patient’s potassium levels and adjust dose appropriately in patients who develop hyperkalemia.

Common side effects of eplerenone include:

• Hyperkalemia
• Increase in serum creatinine
• Renal insufficiency
• Chest pain associated with coronary artery disease (angina pectoris)
• Myocardial infarction
• Headache
• Dizziness
• Increased gamma-glutamyl transferase
• Abnormal breast tissue growth in men (gynecomastia)
• Abnormal vaginal hemorrhage
• Skin rash
• Swelling beneath the skin and mucous membranes (angioedema)

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet

• 25 mg
• 50 mg

Adult:

Hypertension (HTN)

• Initial 50 mg orally once daily; may increase to 50 mg orally every 12 hours; may take up to four weeks for a full therapeutic response; hyperkalemia may occur with doses above 100 mg/day

Heart Failure Post MI

• Initial 25 mg orally once daily; may titrate to a maximum of 50 mg once daily within 4 weeks as tolerated
• Dose adjustments may be required based on potassium levels

Renal Impairment

• Contraindicated if creatinine clearance (CrCl) is below 50 mL/minute or serum creatinine above 2 mg/dL in males or above 1.8 mg/dL in females

Hepatic Impairment

• Dose adjustment not necessary

Dosing considerations

• In post-MI CHF 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

Other Indications and Uses

• Improving survival of stable patients with LV systolic dysfunction (LVEF 40% or less) and CHF after an acute myocardial infarction (MI)

Geriatric:

Hypertension

• Initial 50 mg orally once daily; may increase to 50 mg orally every 12 hours; may take up to four weeks for a full therapeutic response; hyperkalemia may occur with doses above 100 mg/day

Heart Failure Post MI

• Initial 25 mg orally once daily; may titrate to a maximum of 50 mg once daily within 4 weeks as tolerated
• Dose adjustments may be required based on potassium levels

Pediatric:

• Safety and efficacy not established

Overdose

• There has been no report of a human overdose of eplerenone. Animal studies show eplerenone overdose can cause salivation, vomiting, tremor, sedation, and convulsions.
• Overdose in humans is likely to cause hypotension and hyperkalemia. Treatment for an overdose may include activated charcoal to eliminate undigested drugs and appropriate treatment for hypotension and hyperkalemia.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of eplerenone include:
  • chloramphenicol
  • cobicistat
  • itraconazole
  • lopinavir
  • mifepristone
  • nefazodone
  • nirmatrelvir/ritonavir
  • saquinavir
  • tipranavir
• Serious interactions of eplerenone include:
  • abametapir
  • amiloride
  • apalutamide
  • diltiazem
  • drospirenone
  • enzalutamide
  • fexinidazole
  • idelalisib
  • isoniazid
  • ketoconazole
  • levoketoconazole
  • lofexidine
  • potassium acid phosphate
  • potassium chloride
  • potassium phosphates, IV
  • spironolactone
  • triamterene
  • tucatinib
  • voxelotor
• Eplerenone has moderate interactions with at least 74 different drugs.
• Eplerenone has mild interactions with at least 96 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• There are no adequate and well-controlled studies on the safety of eplerenone use in pregnant women. Eplerenone should be used in pregnancy only if potential maternal benefits outweigh the potential risk to the fetus.
• There is no information on the presence of eplerenone in human breastmilk, however, it is present in animal milk, and likely excreted in human breastmilk also. Decision should be made to discontinue the drug or nursing because of the unknown potential for adverse reactions in the breastfed infant.

• Take eplerenone exactly as prescribed.
• Do not take potassium supplements or potassium containing drugs while on eplerenone therapy, without first checking with your physician.
• Contact your physician if you experience symptoms such as dizziness, diarrhea, vomiting, rapid or irregular heartbeat, lower extremity edema, or difficulty breathing.
• Store safely out of reach of children.
• In case of overdose, seek medical help or contact Poison Control.