Chemical formula: C₂₄H₃₀O₆ Molecular mass: 414.491 g/mol PubChem compound: 443872
Eplerenone interacts in the following cases:
Co-administration of eplerenone 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.
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.
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. Periodic monitoring of serum potassium is recommended.
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.
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 coadministration.
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.
Co-administration of these drugs with eplerenone may potentially increase antihypertensive effects and risk of postural hypotension.
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.
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.
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. Co-administration of eplerenone and lithium should be avoided. If this combination appears necessary, lithium plasma concentrations should be monitored.
Co-administration of these drugs with eplerenone may potentially decrease antihypertensive effects (sodium and fluid retention).
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.
No clinically significant pharmacokinetic interactions have been observed with warfarin. Caution is warranted when warfarin is dosed near the upper limit of therapeutic range.
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.
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 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.
There are no human data available on fertility.
No studies on the effect of eplerenone on the ability to drive or use machines have been performed. Eplerenone does not cause drowsiness or impairment of cognitive function but when driving vehicles or operating machines it should be taken into account that dizziness may occur during treatment.
In two studies (EPHESUS and Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure [EMPHASIS-HF]), the overall incidence of adverse events reported with eplerenone was similar to placebo.
Adverse events reported below are those with suspected relationship to treatment and in excess of placebo or are serious and significantly in excess of placebo, or have been observed during post marketing surveillance.
Adverse events are listed by body system and absolute frequency. Frequencies are defined as: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data).
ADR Frequency in Eplerenone Placebo Controlled Studies:
Uncommon: pyelonephritis, infection, pharyngitis
Uncommon: eosinophilia
Uncommon: hypothyroidism
Common: hyperkalaemia, hypercholesterolaemia
Uncommon: hyponatraemia, dehydration, hypertriglyceridaemia
Common: insomnia
Common: syncope, dizziness, headache
Uncommon: hypoaesthesia
Common: left ventricular failure, atrial fibrillation
Uncommon: tachycardia
Common: hypotension
Uncommon: arterial thrombosis limb, orthostatic hypotension
Common: cough
Common: diarrhoea, nausea, constipation, vomiting
Uncommon: flatulence
Common: rash, pruritus
Uncommon: angioedema, hyperhidrosis
Common: muscle spasms, back pain
Uncommon: musculoskeletal pain
Common: renal impairment
Uncommon: cholecystitis
Uncommon: gynaecomastia
Common: asthenia
Uncommon: malaise
Common: blood urea increased, blood creatinine increased
Uncommon: epidermal growth factor receptor decreased, blood glucose increased
In EPHESUS, there were numerically more cases of stroke in the very elderly group (≥75 years old). There was however no statistical significant difference between the occurrence of stroke in the eplerenone (30) vs placebo (22) groups. In EMPHASIS-HF, the number of cases of stroke in the very elderly (≥75 years old) was 9 in the eplerenone group and 8 in the placebo group.
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