Eplerenone

Uses

Congestive heart failure after an acute myocardial infarction, Hypertension.

Eplerenone is also used to associated treatment for these conditions: High Blood Pressure (Hypertension), LVEF <40% Congestive heart failure, Chronic heart failure with reduced ejection fraction (NYHA Class II)

How Eplerenone works

Eplerenone binds to the mineralocorticoid receptor and thereby blocks the binding of aldosterone (component of the renin-angiotensin-aldosterone-system, or 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.

Dosage

Eplerenone dosage

Congestive Heart Failure after an acute Myocardial Infarction:The recommended dose of Eplerenone is 50 mg once daily. Treatment should be initiated at 25 mg once daily and titrated to the target dose of 50 mg once daily preferably within 4 weeks as tolerated by the patient. Eplerenone may be administered with or without food.

Hypertension: Eplerenone may be used alone or in combination with other antihypertensive agents. The recommended starting dose of Eplerenone is 50 mg administered once daily. For patients with an inadequate blood pressure response to 50 mg once daily the dosage of Eplerenone should be increased to 50 mg twice daily. Higher dosages of Eplerenone are not recommended either because they have no greater effect on blood pressure than 100 mg or because they are associated with an increased risk of hyperkalemia.

Side Effects

Headache, dizziness, diarrhea, stomach pain, nausea, cough or flu-like symptoms may occur. Symptoms of a serious allergic reaction like: rash, itching, swelling, severe dizziness, trouble breathing can occur.

Toxicity

The most likely symptoms of human overdosage would be anticipated to be hypotension or hyperkalemia. However, no cases of human overdosage with eplerenone have been reported.

Precaution

Eplerenone should be used with caution in hyperkalemia, severe kidney disease, diabetic patients with congestive heart failure after an acute myocardial infarction including those with proteinuria.

Interaction

May increase risk of hyperkalaemia with ACE inhibitors and/or angiotension receptor blocker, ciclosporin, tacrolimus, trimethoprim. May reduce antihypertensive effect with NSAIDs, glucocorticoids, tetracosactide. May enhance hypotensive effect of α1-blockers (e.g. alfuzosin, prazosin), TCAs, amifostine, baclofen, neuroleptics. May increase plasma level with mild to moderate CYP3A4 inhibitors (e.g. fluconazole, erythromycin, saquinavir, amiodarone, diltiazem, verapamil).

Food Interaction

• Avoid grapefruit products. Grapefruit juice may increase the serum levels of eplerenone by 25% by inhibiting CYP3A4.
• Take with or without food.

Eplerenone Alcohol interaction

[Moderate]

Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation.

Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

Caution and close monitoring for development of hypotension is advised during coadministration of these agents.

Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs.

Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

Eplerenone Drug Interaction

Moderate: aspirin, aspirin, sacubitril / valsartan, sacubitril / valsartanUnknown: apixaban, apixaban, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, furosemide, furosemide, metoprolol, metoprolol, clopidogrel, clopidogrel, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol

Eplerenone Disease Interaction

Major: diabetes type II and microalbuminuria, hyperkalemia, renal dysfunctionModerate: liver disease

Volume of Distribution

• 43 to 90 L

Elimination Route

The absolute bioavailability of eplerenone is unknown.

Half Life

4-6 hours

Clearance

• Apparent plasma cl=10 L/hr

Pregnancy & Breastfeeding use

Pregnancy: There are no adequate and well-controlled studies in pregnant women. Eplerenone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: The concentration of Eplerenone in human breast milk after oral administration is unknown. Because many drugs are excreted in human milk and because of the unknown potential for adverse effects on the 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 mother.

Contraindication

Eplerenone is contraindicated in-

• Hyperkalaemia
• Severe renal impairment (creatinine clearance less than 30 ml/min)
• Severe hepatic impairment
• Concomitant use with potent CYP3A4 inhibitors like Ketoconazole, Itraconazole, Nefazodone, Troleandomycin, Clarithromycin, Ritonavir, and Nelfinavir or other
• Potassium-sparing diuretics are also contraindicated

Special Warning

Pediatric use: The safety and effectiveness of Eplerenone has not been established in pediatric patients.

Geriatric use: No differences in overall incidence of effectivity or safety was observed in elderly patients.

Acute Overdose

Symptoms: Hyperkalaemia, hypotension.

Management: Symptomatic and supportive treatment. Admin activated charcoal. Initiate standard therapy for hyperkalaemia.

Storage Condition

Store below 30°C in a cool and dry place, protected from light and moisture. Keep out of children’s reach.

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