Presentation and Status in Health Basket
Film Coated Tablets
28 X 25 mg
Film Coated Tablets
28 X 50 mg
For the individual adjustment of dose, the strengths of 25 mg and 50 mg are available. The maximum dose regimen is 50 mg daily.
For post-MI heart failure patients: The recommended maintenance dose of eplerenone is 50 mg once daily (OD). Treatment should be initiated at 25 mg once daily and titrated to the target dose of 50 mg once daily preferably within 4 weeks, taking into account the serum potassium level (see Table 1 at the attached doctor’s leaflet). Eplerenone therapy should usually be started within 3-14 days after an acute MI.
For patients with NYHA class II (chronic) heart failure: For chronic heart failure NYHA class II patients, treatment should be initiated at a dose of 25 mg once daily and titrated to the target dose of 50 mg once daily preferably within 4 weeks; taking into account the serum potassium level (see Table 1 at the attached doctor’s leaflet).
Patients with a serum potassium of > 5.0 mmol/L should not be started on eplerenone.
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.
After initiation, the dose should be adjusted based on the serum potassium level as shown in Table 1 at the attached doctor’s leaflet.
Following withholding eplerenone due to serum potassium ≥ 6.0 mmol/L, eplerenone can be re-started at a dose of 25 mg every other day when potassium levels have fallen below 5.0 mmol/L.
Paediatric population: The safety and efficacy of eplerenone in children and adolescents have not been established.
Elderly: No initial dose adjustment is required in the elderly. Due to an age-related decline in renal function, the risk of hyperkalaemia is increased in elderly patients. This risk may be further increased when co-morbidity associated with increased systemic exposure is also present, in particular mild-to-moderate hepatic impairment. Periodic monitoring of serum potassium is recommended.
Renal impairment: No initial dose adjustment is required in patients with mild renal impairment. Periodic monitoring of serum potassium with dose adjustment according to Table 1 is recommended.
Patients with moderate renal impairment (CrCl 30-60 mL /min) should be started at 25 mg every other day, and dose should be adjusted based on the potassium level (see Table 1). Periodic monitoring of serum potassium is recommended.
There is no experience in patients with CrCl <50 mL /min with post MI heart failure. The use of eplerenone in these patients should be done cautiously. Doses above 25 mg daily have not been studied in patients with CrCl <50 mL/min.
Use in patients with severe renal impairment (CrCl <30 mL /min) is contraindicated. Eplerenone is not dialysable.
Hepatic impairment: No initial dose adjustment is necessary for patients with mild-to-moderate hepatic impairment. Due to an increased systemic exposure to eplerenone in patients with mild-to-moderate hepatic impairment, frequent and regular monitoring of serum potassium is recommended in these patients, especially when elderly.
Concomitant treatment: In case of concomitant treatment with mild to moderate CYP3A4 inhibitors, e.g. amiodarone, diltiazem, erythromycin, saquinavir and verapamil, the dose of 25 mg OD may be initiated. Dosing should not exceed 25 mg OD.
Eplerenone may be administered with or without food.
Inspra® is indicated:
• in addition to standard therapy including beta-blockers, to reduce the risk of cardiovascular (CV) mortality and morbidity in stable patients with left ventricular dysfunction (LVEF ≤ 40 %) and clinical evidence of heart failure after recent myocardial infarction (MI).
• in addition to standard optimal therapy, to reduce the risk of CV mortality and morbidity in adult patients with New York Heart Association ( NYHA) class II (chronic) heart failure and left ventricular systolic dysfunction (LVEF ≤30%).
Hypersensitivity to the active substance or to any of the excipients.
Patients with serum potassium level > 5.0 mmol/L at initiation.
Patients with severe renal insufficiency (eGFR <30 mL per minute per 1.73 m²).
Patients with severe hepatic insufficiency (Child-Pugh Class C).
Patients receiving potassium-sparing diuretics, or strong inhibitors of CYP 3A4 (e.g., itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycin, telithromycin and nefazodone).
The combination of an angiotensin converting enzyme (ACE) inhibitor and an angiotensin receptor blocker (ARB) with eplerenone.
Hyperkalaemia: Consistent with its mechanism of action, hyperkalaemia may occur with eplerenone. Serum potassium levels should be monitored in all patients at initiation of treatment and with a change in dosage. Thereafter, periodic monitoring is recommended especially in patients at risk for the development of hyperkalaemia, such as elderly patients, patients with renal insufficiency and patients with diabetes. The use of potassium supplements after initiation of eplerenone therapy is not recommended, due to an increased risk of hyperkalaemia. Dose reduction of eplerenone has been shown to decrease serum potassium levels. In one study, the addition of hydrochlorothiazide to eplerenone therapy has been shown to offset increases in serum potassium. The risk of hyperkalaemia may increase when eplerenone is used in combination with an ACE inhibitor and/or an ARB. The combination of an ACE inhibitor and an ARB with eplerenone should not be used.
Impaired renal function: Potassium levels should be monitored regularly in patients with impaired renal function, including diabetic microalbuminuria. The risk of hyperkalaemia increases with decreasing renal function. While the data from Eplerenone Post-acute Myocardial Infarction Heart failure Efficacy and Survival Study (EPHESUS) in patients with Type 2 diabetes and microalbuminuria is limited, an increased occurrence of hyperkalaemia was observed in this small number of patients. Therefore, these patients should be treated with caution. Eplerenone is not removed by haemodialysis.
Impaired hepatic function: No elevations of serum potassium above 5.5 mmol/L were observed in patients with mild to moderate hepatic impairment (Child Pugh class A and B). Electrolyte levels should be monitored in patients with mild to moderate hepatic impairment. The use of eplerenone in patients with severe hepatic impairment has not been evaluated and its use is therefore contraindicated.
CYP3A4 inducers: Coadministration of eplerenone with strong CYP3A4 inducers is not recommended.
Lithium, cyclosporin, tacrolimus: should be avoided during treatment with eplerenone.
Lactose: The tablets contain lactose and should not be administered in patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
Hyperkalaemia, hypercholesterolaemia, hyponatraemia, dehydration, hypertriglyceridaemia, insomnia, syncope, dizziness, headache, left ventricular failure, atrial fibrillation, rash, pruritus, muscle spasms, back pain, asthenia, blood urea increased, blood creatinine increased.
See prescribing information for full details.
Potassium-sparing diuretics and potassium supplements: Due to increased risk of hyperkalaemia, eplerenone should not be administered to patients receiving other potassium-sparing diuretics and potassium supplements. Potassium-sparing diuretics may also potentiate the effect of anti-hypertensive agents and other diuretics.
ACE inhibitors, ARBs: The risk of hyperkalaemia may increase when eplerenone is used in combination with an ACE inhibitor and/or an ARB. A close monitoring of serum potassium and renal function is recommended, especially in patients at risk for impaired renal function, e.g., the elderly. The triple combination of an ACE inhibitor and an ARB with eplerenone should not be used.
Lithium: Drug interaction studies of eplerenone have not been conducted with lithium. However, lithium toxicity has been reported in patients receiving lithium concomitantly with diuretics and ACE inhibitors. Coadministration of eplerenone and lithium should be avoided. If this combination appears necessary, lithium plasma concentrations should be monitored.
Cyclosporin, tacrolimus: Cyclosporin and tacrolimus may lead to impaired renal function and increase the risk of hyperkalaemia. The concomitant use of eplerenone and cyclosporin or tacrolimus should be avoided. If needed, close monitoring of serum potassium and renal function are recommended when cyclosporine and tacrolimus are to be administered during treatment with eplerenone.
Non-steroidal anti-inflammatory drugs (NSAIDs): Treatment with NSAIDs may lead to acute renal failure by acting directly on glomerular filtration, especially in at-risk patients (elderly and/or dehydrated patients). Patients receiving eplerenone and NSAIDs should be adequately hydrated and be monitored for renal function prior to initiating treatment.
Trimethoprim: The concomitant administration of trimethoprim with eplerenone increases the risk of hyperkalaemia. Monitoring of serum potassium and renal function should be made, particularly in patients with renal impairment and in the elderly.
Alpha-1-blockers (e.g. prazosin, alfuzosine): When alpha-1-blockers are combined with eplerenone, there is the potential for increased hypotensive effect and/or postural hypotension. Clinical monitoring for postural hypotension is recommended during alpha-1-blocker co-administration.
Tricyclic anti-depressants, neuroleptics, amifostine, baclofene: Co-administration of these drugs with eplerenone may potentially increase antihypertensive effects and risk of postural hypotension.
Glucocorticoids, tetracosactide: Co-administration of these drugs with eplerenone may potentially decrease antihypertensive effects (sodium and fluid retention).
In vitro studies indicate that eplerenone is not an inhibitor of CYP1A2, CYP2C19, CYP2C9, CYP2D6 or CYP3A4 isozymes. Eplerenone is not a substrate or an inhibitor of P-Glycoprotein.
Digoxin: Systemic exposure (AUC) to digoxin increases by 16% (90% CI: 4% – 30%) when co-administered with eplerenone. Caution is warranted when digoxin is dosed near the upper limit of therapeutic range.
Warfarin: No clinically significant pharmacokinetic interactions have been observed with warfarin. Caution is warranted when warfarin is dosed near the upper limit of therapeutic range.
CYP3A4 substrates: Results of pharmacokinetic studies with CYP3A4 probe-substrates, i.e. midazolam and cisapride, showed no significant pharmacokinetic interactions when these drugs were coadministered with eplerenone.
– Strong CYP3A4 inhibitors: Significant pharmacokinetic interactions may occur when eplerenone is coadministered with drugs that inhibit the CYP3A4 enzyme. A strong inhibitor of CYP3A4 ( ketoconazole 200 mg BID) led to a 441% increase in AUC of eplerenone. The concomitant use of eplerenone with strong CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin, telithromycin and nefazadone, is contra-indicated.
– Mild to moderate CYP3A4 inhibitors: Co-administration with erythromycin, saquinavir, amiodarone, diltiazem, verapamil, or fluconazole has led to significant pharmacokinetic interactions with rank order increases in AUC ranging from 98% to 187%. Eplerenone dosing should therefore not exceed 25 mg daily when mild to moderate inhibitors of CYP3A4 are co-administered with eplerenone.
CYP3A4 inducers: Co-administration of St John’s wort (a strong CYP3A4 inducer) with eplerenone caused a 30 % decrease in eplerenone AUC. A more pronounced decrease in eplerenone AUC may occur with stronger CYP3A4 inducers such as rifampicin. Due to the risk of decreased eplerenone efficacy, the concomitant use of strong CYP3A4 inducers (rifampicin, carbamazepine, phenytoin, phenobarbital, St John’s wort) with eplerenone is not recommended.
Antacids: Based on the results of a pharmacokinetic clinical study, no significant interaction is expected when antacids are coadministered with eplerenone.
Pregnancy and Lactation
Pregnancy: There are no adequate data on the use of eplerenone in pregnant women. Caution should be exercised prescribing eplerenone to pregnant women.
Lactation: It is unknown if eplerenone is excreted in human breast milk after oral administration. Because of the unknown potential for adverse effects on the breast fed infant, a decision should be made whether to discontinue breast-feeding or discontinue the drug, taking into account the importance of the drug to the mother.
See prescribing information for full details.
No cases of adverse events associated with overdose of eplerenone in humans have been reported. The most likely manifestation of human overdose would be anticipated to be hypotension or hyperkalaemia. Eplerenone cannot be removed by haemodialysis. Eplerenone has been shown to bind extensively to charcoal. If symptomatic hypotension should occur, supportive treatment should be initiated. If hyperkalaemia develops, standard treatment should be initiated.
Storage: Store below 25ºC.