Eplerenone

Registered South African indications:

• Reduce the risk of cardiovascular death in stable patients with left ventricular dysfunction (LVEF ≤40%) and clinical evidence of heart failure after recent myocardial infarction (MI)

Contraindications 

• Hypersensitivity to the active ingredient or any of its excipients
• Serum potassium >5mmol/L at initiation
• Severe renal impairment (eGFR <30ml/min/1.73m²)
• Severe hepatic impairment (Child-Pugh Class C)
• Coadministration with potassium-sparing diuretics
• Coadministration with CYP3A4 inhibitors
• Coadministration with angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker

Cautions 

• Pregnancy
• Breastfeeding
• Mild to moderate renal impairment
• Mild to moderate hepatic impairment
• Elderly
• Diabetic patients
• Diabetic microalbuminuria
• Warfarin dosing near the upper limit of therapeutic range
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab

Reduce the risk of cardiovascular mortality and morbidity (additional agents required)
- In addition to standard therapy including beta-blockers in stable patients with left ventricular dysfunction (LVEF ≤40%) and clinical evidence of heart failure after recent myocardial infarction
- In addition to standard optimal therapy in patients with New York Heart Association class II (chronic) heart failure and left ventricular systolic dysfunction (LVEF ≤30%)

• Oral (tab): Initial: 25mg, dly; Titrate to target maintenance dose within 4 weeks; Maintenance: 50mg, dly (*see additional prescribing points)

Start within 3-14 days of acute myocardial infarction

Serum potassium should be measured before initiating eplerenone therapy, within the first week and at one month after the start of treatment or dose adjustment. Serum potassium should be assessed as needed periodically thereafter

Patients with serum potassium >5.0mmol/L should not be started on eplerenone

After initiation, the dose should be adjusted based on serum potassium level. See additional prescribing points

Not established for use in children

Pregnancy

• Caution
• There are no adequate data on the use of eplerenone in pregnant women
• Animal studies did not indicate direct or indirect adverse effects with respect to pregnancy, embryofoetal development, parturition and postnatal development
• Caution should be exercised prescribing eplerenone to pregnant women

Breastfeeding

• Caution; not recommended
• It is unknown if eplerenone is excreted in human breast milk after oral administration. However, preclinical data show that eplerenone and/or metabolites are present in rat breast milk and that rat pups exposed by this route developed normally
• Because of the unknown potential for adverse effects on the breastfed infant, a decision should be made whether to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother

Fertility

• There are no human data available on fertility

Renal Impairment

• Mild: Caution; no dose adjustment recommended
  No initial dose adjustment is required. Periodic monitoring of serum potassium with dose adjustment is recommended (see additional prescribing points)
• Moderate: Caution; dose adjustment recommended
  Start at 25mg every other day, and dose should be adjusted based on the potassium level (see additional prescribing points). Periodic monitoring of serum potassium is recommended
  There is no experience in patients with CrCl <50ml/min with post-myocardial infarction heart failure. The use of eplerenone in these patients should be done cautiously. Doses above 25mg daily have not been studied in patients with CrCl <50ml/min
• Severe: Contraindicated
  Eplerenone is not dialysable

Hepatic Impairment

• Mild to moderate (Child-Pugh Classes A & B): Caution; no dose adjustment recommended 
  Due to an increased systemic exposure to eplerenone in these patients, frequent and regular monitoring of serum potassium is recommended, especially when elderly
• Severe (Child-Pugh Class C): Contraindicated

Elderly

• Caution; no dose adjustment recommended 
  No initial dose adjustment is required. Due to an age-related decline in renal function, the risk of hyperkalaemia is increased in the elderly. This risk may be further increased when co-morbidity associated with increased systemic exposure is also present, in particular with mild-to-moderate hepatic impairment. Periodic monitoring of serum potassium is recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Prohibited - At all times

Central Nervous System Disorders

• Insomnia
• Dizziness
• Syncope
• Headache
• Hypoaesthesia
• Asthenia

Cardiovascular Disorders

• Left ventricular failure
• Atrial fibrillation
• Tachycardia
• Hypotension
• Limb arterial thrombosis
• Orthostatic hypotension

Respiratory Disorders

• Cough
• Pharyngitis

Gastrointestinal Disorders

• Diarrhoea
• Nausea and vomiting
• Constipation
• Flatulence

Hepatobiliary Disorders

• Cholecystitis

Genitourinary Disorders

• Gynaecomastia
• Pyelonephritis
• Renal impairment
• Increased blood urea
• Increased blood creatinine

Endocrine and Metabolic Disorders

• Hyperkalaemia
• Hypercholesterolaemia
• Hyponatraemia
• Dehydration
• Hypertriglyceridaemia
• Hypothyroidism
• Decreased epidermal growth factor receptor
• Increased blood glucose

Musculoskeletal Disorders

• Muscle spasms
• Back pain
• Musculoskeletal pain

Skin and Subcutaneous Tissue Disorders

• Rash
• Pruritus
• Hyperhidrosis
• Angioedema

Immune, Blood and Lymphatic System Disorders

• Infection
• Eosinophilia

• CYP3A4 inhibitors
• Itraconazole
• Ketoconazole
• Ritonavir
• Nelfinavir
• Clarithromycin
• Telithromycin
• Nefazodone
• Erythromycin
• Saquinavir
• Amiodarone
• Diltiazem
• Verapamil
• Fluconazole
• CYP3A4 inducers
• Rifampicin
• Carbamazepine
• Phenytoin
• Phenobarbital
• Potassium-sparing diuretics
• Potassium supplements
• Angiotensin-converting enzyme inhibitors
• Angiotensin receptor blockers
• Lithium
• Cyclosporin
• Tacrolimus
• Non-steroidal anti-inflammatory drugs
• Trimethoprim
• Alpha-1 blockers
• Prazosin
• Alfuzosin
• Tricyclic antidepressants
• Neuroleptics
• Amifostine
• Baclofen
• Glucocorticoids
• Tetracosactide
• Digoxin

Other

• St John's wort

• Blood pressure
• Serum potassium

None routine. Specific cases may require

• Serum creatinine
• Renal function

Recommended dosage adjustment after initiation

After initiation of treatment, dose adjustment should be dependant on serum potassium as shown in the table below:

Once potassium levels are below 5.0mmol/L, eplerenone can be restarted at 25mg, dly

Eplerenone has relative selectivity in binding to recombinant human mineralocorticoid receptors compared to its binding to recombinant human glucocorticoid, progesterone and androgen receptors. Eplerenone prevents the binding of aldosterone, a key hormone in the renin-angiotensin-aldosterone-system (RAAS), which is involved in the regulation of blood pressure and the pathophysiology of CV disease.

Tablet 25mg

• Inspra (UpJohn) originator

Tablet 50mg

• Inspra (Pfizer) originator