Inspra (Eplerenone) Side Effects and Risks

High Potassium and other side effects of eplerenone

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Eplerenone, known by the brand name Inspra, is prescribed for the treatment of hypertension (high blood pressure) and heart failure. This medication has resulted in reduced blood pressure and improved survival for those who have had heart failure after a heart attack.

Healthcare provider taking blood pressure
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Common Eplerenone Side Effects

Many of the common side effects of Inspra (eplerenone) tend to resolve as your body adapts to the medication. Call your healthcare provider if any of these side effects persist or worsen:

  • Headache
  • Dizziness
  • Coughing
  • Flu-like symptoms
  • Tiredness
  • Diarrhea

Check with your healthcare provider for suggestions on how to prevent or reduce possible side effects. Do not stop taking your medication without contacting your healthcare provider. Depending upon the side effects, the healthcare provider may want to change your medication, modify your dosage, or continue the medication and see if the side effects resolve over time.

Serious Eplerenone Side Effects

Eplenerone may produce a variety of serious side effects.

High Potassium

Eplerenone is a potassium-sparing diuretic, which means that it avoids the potential potassium loss that occurs with other diuretics that remove the body’s potassium. In some ways, this is positive, as potassium reduces the risk of heart disease and stroke by lowering blood pressure. But, too much potassium can be detrimental too.

A normal potassium level is between 3.5 and 5.0 mEq/L. A simple blood test can show the level of potassium in your blood.

Some symptoms of high potassium that may develop over several weeks or even months are:

  • Muscle weakness
  • Numbness
  • Tingling
  • Nausea

For people who have very high levels of potassium or if the increase in potassium happens very suddenly, side effects may be more serious. These side effects can be life-threatening and may require immediate medical care. If you have the following symptoms, call 911, or go to the emergency room:

  • Heart palpitations
  • Shortness of breath
  • Chest pain
  • Nausea
  • Vomiting

When potassium levels are abnormally elevated, the result could be a condition called hyperkalemia, which, if left untreated can cause muscle weakness, paralysis, cardiac arrhythmias, and sudden cardiac death.

People who have hyperkalemia events can recover by discussing the possible change of the dose of the anti-diuretic medication or discontinuing the medication and prescribing another medication.

Kidney Problems

Patients with chronic or advanced kidney disease are at high risk for hyperkalemia, especially when other factors are involved that interfere with potassium being excreted (removed) through the kidneys.

The prevalence of hyperkalemia in patients with chronic kidney disease is considerably higher than in the general population. For these patients, the healthcare providers will determine a treatment to remove the potassium from the body. One way to reduce the body’s potassium is to implement a low-potassium diet and avoid potassium-containing salt substitutes.

If other measures to remove the potassium don’t work, the healthcare provider may recommend potassium-binding medications that bind to extra potassium in your stool. These medicines are often in powdered form and are mixed with water to either drink in some forms, or in enema form depending on the person’s needs.


Eplerenone is not recommended as a blood pressure medication for patients with type 2 diabetes with microalbuminuria. Hyperkalemia occurs more frequently in people with diabetes, particularly when eplerenone is given with angiotensin-converting enzyme (ACE) inhibitors; 38% of people receiving this combination had hyperkalemia.

The Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy And Survival Study (EPHESUS) showed that diabetic patients with congestive heart failure after a heart attack, especially those with the presence of abnormal amounts of protein in their urine (proteinuria), had increased rates of hyperkalemia compared to patients who just had either diabetes or proteinuria.

Severe Side Effects

Angina (chest pain) can occur and is among the most common reasons for discontinuation of Inspra in people with hypertension.

Less Common, But Possible Side Effects

Eplerenone can have androgenic effects (pertaining to male characteristics), such as:

  • Irregular periods
  • Gynecomastia (enlargement of male breasts)
  • Voice changes
  • Hirsutism (abnormal hair growth)

How to Take

Inspra is available as 25- and 50-milligram (mg) oral tablets. The dosage varies depending upon the person’s condition:

  • Hypertension: 50 mg once daily for four weeks. If blood pressure is not controlled, the healthcare provider may increase the dose to twice daily. Studies have shown that doses higher than 100 mg daily do not provide any greater control and may only increase the risk of hyperkalemia.
  • Congestive heart failure with myocardial infarction: 25 mg daily and increased to 50 mg within four weeks. Thereafter, the dose is regularly adjusted based on your blood potassium levels. If levels exceed 6.0, treatment is temporarily stopped until levels become more normal.

Inspra may also be recommended for those who have symptomatic heart failure with a reduced ejection fraction.

These listed dosages are according to the drug manufacturer. Each person has different needs, so discuss your prescription with your healthcare provider to make sure your dose is right for you.

Inspra dose should not exceed 25 mg daily for people with congestive heart failure who take certain moderate CYP3A4 inhibitors.

If you miss a dose, take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose, and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.


Possible drug interactions include some antibiotics, antifungal medications, mood stabilizers, and antiviral medicine that treat HIV/AIDS.

CYP3A Inhibitors

Interactions are possible with:

  • Weak CYP3A inhibitors: Cimetidine
  • Moderate CYP3A4 inhibitors: Amiodarone, erythromycin, fluconazole, miconazole, diltiazem, verapamil, delavirdine, amprenavir, fosamprenavir, conivaptan
  • Strong CYP3A inhibitors: Do not use Inspra with drugs that are strong inhibitors of CYP3A, such as clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir.

ACE Inhibitors and ARBs

The risk of hyperkalemia increases when eplerenone is used in combination with an angiotensin-converting enzyme (ACE) inhibitor and/or an angiotensin II receptor antagonist (ARB). Close monitoring of serum potassium and renal function is recommended, especially in patients at risk for impaired renal function, such as the elderly.


Lithium toxicity has been reported in patients receiving lithium at the same time with diuretics and ACE inhibitors. Since a drug interaction study of eplerenone with lithium has not been conducted, serum lithium levels should be monitored frequently if Inspra is administered at the same time as lithium.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDS)

A drug interaction study of eplerenone with an NSAID has not been conducted, but the use of other potassium-sparing blood pressure medications with NSAIDs has been shown to reduce the antihypertensive (blood-pressure lowering) effect in some patients and result in severe hyperkalemia in patients with impaired or weakened kidney function.

Therefore, when Inspra and NSAIDs are used at the same time, blood pressure and serum potassium levels should be monitored.

Food Interactions

Talk to your healthcare provider about any issues that may develop from drinking grapefruit juice while taking this medicine. Eplerenone has been noted on a high grapefruit interaction list for possibly developing hyperkalemia and serious heart arrhythmias.

Do not use salt substitutes containing potassium while you are taking eplerenone. If your healthcare provider prescribes a low-salt or low-sodium diet, follow the healthcare provider's directions carefully.

Possible Allergies

As with any medication, contact your healthcare provider immediately or go to the emergency room if you are experiencing these allergic reaction symptoms:

  • Hives
  • Itching
  • Rash
  • Trouble breathing
  • Chest Tightness
  • Swelling of your lips, tongue, and throat

Warnings and Precautions

Eplerenone may not be appropriate for some populations.


There have been no adequate and well-controlled studies in people who are pregnant. so Inspra should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Inspra should be used during pregnancy only if clearly needed.


The concentration of eplerenone in human breast milk after oral administration is unknown; however, studies with rats show that eplerenone and/or metabolites are present in rat breast milk obtained after a single oral dose.

Because of the unknown potential for adverse effects on a nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the adult.

Pediatric Use

In a study of pediatric patients age 4 to 17 with high blood pressure, using doses that produced exposure similar to that in adults, Inspra did not lower blood pressure effectively.

Inspra has not been studied in hypertensive patients less than 4 years old because the study in older pediatric patients did not demonstrate effectiveness. Inspra has not been studied in pediatric patients with heart failure.

Geriatric Use

Patients greater than 75 years did not appear to benefit from the use of Inspra. However, due to age-related decreases in clearing creatinine (a waste product filtered by the kidneys) from the body, the incidence of laboratory-documented hyperkalemia has been increased in some patients 65 and older.

A Word From Verywell

Taking eplerenone can’t prevent all of those blood pressure-raising events that you face each day, but it can help avoid strokes, heart attacks, and kidney problems associated with having high blood pressure. Take your medication regularly, maintain a healthy diet, exercise, and stay aware of any side effects that you may be experiencing.

12 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By Mali Schantz-Feld
Mali Schantz-Feld is a medical journalist with over 25 years of experience covering a wide range of health, medicine, and dental topics.