What to Know About Inspra (Eplerenone)

Diuretic Drug Used to Treat High Blood Pressure and Heart Failure

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Inspra (eplerenone) is a type of diuretic drug (“water pill”) available in tablet form used to treat high blood pressure in adults as well as heart failure following a heart attack. Approved for use in the United States in 2002, Inspra is available in generic forms.

It belongs to a class of drugs called mineralocorticoid receptor antagonists that block the action of the hormone aldosterone which helps to regulate sodium and water, and therefore blood pressure, in the body. This class of drugs belongs to a larger group of diuretics referred to as potassium-sparing diuretics.

Man checks blood pressure and prepares to take medications
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Uses

A diuretic is a medication that increases urine production by causing the kidneys to remove more sodium and water from the body. As the water is removed, the blood vessel walls relax, and since the heart has less to pump with each beat, blood pressure lowers.

While some diuretics deplete the body’s potassium, eplerenone is known as a potassium-sparing diuretic, which avoids potential potassium loss. Inspra produces similar results to a popular drug of the same class called Aldactone (spironolactone), but with fewer side effects.

Since this medication does not remove potassium, levels of this mineral can become too high, which can cause dangerous heart rhythm problems and even cardiac arrest. While on this type of medication, ask your doctor whether you need periodic testing of your potassium and kidney function.

Approved indications for treatment with eplerenone include:

EPHESUS Study

In 2003, the Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) tested the hypothesis that treatment with eplerenone reduces overall death rate, cardiovascular death rate, and hospitalization among patients with heart attacks and heart failure for people who are receiving optimal medical therapy.

The trial demonstrated that Inspra reduced the risk of death, cardiovascular death, and sudden cardiac death by 15%, 17%, and 21% respectively in people with signs of CHF after a heart attack.

Off-Label Uses

Although not formally approved for such use, eplerenone is being explored as a treatment for central serous chorioretinopathy (CSCR), an eye disease characterized by leaking of the fluid under the retina.

CSCR is a common cause of visual impairment in people 30-50 years old, and has been estimated as the fourth most frequently encountered non-surgical retinopathy after age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion. For some people, the condition can continue even into the person’s senior years.

This condition is characterized by detachment of the neurosensory retina (the transparent part of the retina) and/or retinal pigment epithelium (the pigmented cell layer just outside the neurosensory retina) with consequent fluid buildup. If the fluid is located outside the macula (the central area of the retina), there may be no symptoms.

But if the detachment affects the central macula, symptoms may include a decrease in the sharpness of vision, metamorphopsia (a defect that causes linear objects, such as lines on a grid, to look curvy or round), changes in image size, decrease in contrast sensitivity, perception of blind spots, or a combination of these symptoms.

Eplerenone targets abnormal changes in body functions that are the causes, consequences, or associated disease processes that may lead to vision improvement and more rapid recovery.

Based on the current literature, eplerenone seems to be efficient, especially at the chronic stage of the disease. At this time, further research is needed to determine which patients are most likely to benefit from eplerenone or its potential combination with other treatment methods.

Before Taking

Inspra is prescribed under specific conditions for hypertension or congestive heart failure.

Hypertension

High blood pressure (HBP) happens when the force of your blood pushing against the walls of your blood vessels is consistently too high. High blood pressure increases the workload of the heart and blood vessels, causing them to work harder and less efficiently.

Over time, the force and friction of high blood pressure can damage the delicate tissues inside the arteries. This causes plaque to form along tiny tears in the artery walls.

The plaque that is formed is low-density lipoprotein (LDL), also known as “bad” cholesterol. As the plaque and damage increase, the inside of the arteries become narrower—raising blood pressure.

High blood pressure can cause:

  • Heart attack and disease
  • Stroke and brain issues
  • Kidney disease
  • Blindness

You can get your blood pressure measured in many places:

  • By a healthcare team member at a doctor’s office
  • At a pharmacy that has a digital blood pressure measurement machine
  • With a home blood pressure monitor that you can use yourself

A normal blood pressure level is less than 120/80 mmHg. Blood pressure is measured using two numbers. The first number, called systolic blood pressure, measures the pressure in your arteries when your heart beats.

The second number, called diastolic blood pressure, measures the pressure in your arteries when your heart rests between beats. If the measurement reads 120 systolic and 80 diastolic, you would say, “120 over 80,” or write, “120/80 mmHg."

More than 1 in 3 Americans may have prehypertension or borderline hypertension, where blood pressures are above the upper boundary of 120/80 mmHg.

Since a blood pressure of 140/90 mm Hg or above is a primary risk factor for heart attack or stroke, the doctor may prescribe medication and recommend lifestyle changes such as cutting back on sodium (salt), weight loss, increasing aerobic activity, quitting smoking, and reducing alcohol consumption.

Even if you take these precautions and feel better, do not stop or reduce your blood pressure medications unless you contact your doctor for guidance.

A study of pediatric patients aged 4-16 years old, treated with Inspra showed that 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.

Congestive Heart Failure

When the heart is unable to pump enough blood to meet the body’s needs, and the heart muscle starts to function inadequately, congestive heart failure can produce fatigue, leg swelling, and shortness of breath.

After testing, which can include blood tests, cardiac ultrasound, and X-ray, treatment can vary depending upon the patient. It may include diet, exercise, anti-hypertensive medications, blood thinners, and heart failure drugs. This condition can occur quickly or over the long term (chronically).

Research has shown that eplerenone appears to reduce the risk of cardiovascular mortality and heart failure after a heart attack by more than one-third. Growing evidence indicates that Inspra may improve outcomes in people with ST-elevation myocardial infarction (STEMI), a serious form of heart attack, even without heart failure.

Precautions and Contraindications

In certain cases, Inspra should be avoided or used with extreme caution:

  • Drug hypersensitivity: Avoid if there is sensitivity to eplerenone or any inactive ingredient in the drug.
  • High potassium: Inspra should not be used if the baseline potassium level is over 5.5. This is the level at which symptoms of hyperkalemia can develop.
  • Kidney failure: This is defined as a creatinine clearance of 30 or less.
  • Type 2 diabetes with microalbuminuria: Microalbuminuria, an increase is albumin in urine, is an indication of some loss of kidney function.
  • CYP3A4 inhibitors: Do not take Inspra if you take drugs that strongly inhibit an enzyme called CYP3A4, which the body uses to metabolize eplerenone. These include Dyazide (hydrochlorothiazide), Modudiretic (amiloride + hydrochlorothiazide), Nizoral (ketoconazole), potassium supplements, and Sporanox (itraconazole).

Another concern is the risk of hyperkalemia, a condition in which potassium levels are abnormally elevated (due in this case to the drug’s potassium-sparing effects). To avoid this potentially dangerous complication, baseline potassium levels must be checked before treatment is started. Thereafter, blood potassium levels must be routinely monitored.

Inspra should be used with extreme caution in people with the following conditions due to an increased risk of hyperkalemia:

  • Decreased kidney function
  • Diabetes
  • Proteinuria (protein in urine)

Other Potassium-Sparing Diuretics

Among mineralocorticoid receptor antagonists, there are only two (Aldactone and Inspra) approved by the FDA.

Finerenone is currently in phase III clinical trials for use in treating chronic kidney disease in people with type 2 diabetes and for treating hypertension. Other experimental potassium-sparing diuretics (esaxerenone and paratenon) are also being investigated.

Another class of potassium-sparing diuretic called epithelial sodium channel blockers have a different mechanism of action. They block the flow of sodium into cells. There are two approved for use in the U.S.: Dyrenium (triamterene) and Midamor (amiloride).

Dosage

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 doctor 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 normalize.

These listed dosages are according to the drug manufacturer. Each person has different needs, so check your prescription and talk to your doctor to make sure you are taking the right dose for you.

Modifications

Inspra dose should not exceed 25 mg daily for people with CHF who take certain moderate CYP3A4 inhibitors such as Diflucan (fluconazole) and erythromycin.

How to Take and Store

Inspra can be taken with or without food. If a dose is missed, it should be taken as soon as possible. If it is near the time of the next dose, skip the dose, and return to the regular dosing schedule. Do not double up on doses. Inspra can be stored safely at temperatures not exceeding 77 F.

Side Effects

Inspra exerts far fewer androgenic effects (pertaining to the development of male characteristics) on the user than Aldactone. Effects such as irregular menstrual periods, gynecomastia, voice changes, and hirsutism (abnormal hair growth), are far less common with Inspra but do occur.

If desiring to avoid androgenic effects, a person might consider that Inspra costs around $350 per month compared to $15 per month for Aldactone.

Common

Many of the common side effects of Inspra tend to resolve as the body adapts to treatment. Call your doctor if the side effects persist or worsen:

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

Severe

Angina (severe chest pain, often also spreading to the shoulders, arms, and neck) can occur and is among the most common reasons for discontinuation of Inspra in people with hypertension.

Hyperkalemia is arguably the most common serious concern and, if left untreated, can lead to cardiac arrhythmia and sudden cardiac arrest (the likelihood of which increases when potassium is over 5.5).

When to Call 911

Seek emergency medical care if signs of hyperkalemia develop, including:

  • Heart palpitations
  • Irregular heart rate
  • Decreased urination
  • Hyperventilation
  • Extreme fatigue and weakness
  • Tingling, numbness, or other sensations
  • Shortness of breath
  • Trouble breathing
  • Nausea and vomiting

Warnings and Interactions

Inspra is a Pregnancy Category B drug, meaning that it is generally regarded as safe, although no well-controlled human studies are available. Animal studies have shown that metabolites of eplerenone are found in breast milk, although the effects this may have on nursing babies is unknown.

If you are a woman of childbearing age, are pregnant, or are nursing, speak with your doctor to fully understand the benefits and risks of treatment.

To avoid interactions and possible complications, advise your doctor about any medications you take, including prescription, over-the-counter, nutritional, herbal, or recreational drugs.

Possible drug interactions include:

  • Weak CYP3A inhibitors: Cimetidine
  • Moderate CYP3A4 inhibitors: Amiodarone, erythromycin, fluconazole, miconazole, diltiazem, verapamil, delavirdine, amprenavir, fosamprenavir, conivaptan
  • Strong CYP3A inhibitors: Clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir.
  • ACE inhibitors and angiotensin II receptor antagonists
  • Lithium
  • Nonsteroidal anti-inflammatory drugs (NSAIDS)
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