Eplerenone dosing

Antihypertensive drug name and dose is associated with compelling indications which are based on benefits from outcome studies or clinical guidelines. For example, the drug class aldosterone antagonists have eplerenone dosed at 25-50 mg per day which is indicated for heart failure patients after an Ml and supported by the EPHESUS trial. 

Initial doses should be low (spironolactone 12.5 mg/day eplerenone 25 mg/day), especially in the elderly and those with diabetes or creatinine clearance <50 mL/min. A spironolactone dose of 25 mg/day was used in one major clinical trial. The eplerenone dose should be titrated to the target dose of 50 mg once daily, preferably within 4 weeks as tolerated by the patient. 

Eplerenone 25 mg once 50 mg once baseline and within 1 week of initiation and dose titration Adverse effects gynecomastia or breast tenderness, menstrual changes, hirsutism... 

In patients without contraindications, spironolactone is initiated at a dose of 12.5 to 25 mg daily, or occasionally on alternate days for patients with baseline renal insufficiency. Eplerenone is used at a dose of 25 mg daily, with the option to titrate up to 50 mg daily. Doses should be halved or switched to alternate-day dosing if creatinine clearance falls below 50 mL/minute. Potassium supplementation is often decreased or stopped after aldosterone antagonists are initiated, and patients should be counseled to avoid high-potassium foods. At anytime after initiation of therapy, if potassium concentrations exceed... 

Either eplerenone or spironolactone should be considered within the first 2 weeks after MI to reduce mortality in all patients already receiving an ACE inhibitor who have LVEF <40% and either heart failure symptoms or a diagnosis of diabetes mellitus. The drugs are continued indefinitely. Example oral doses include the following ... 

Eplerenone 25 mg initially target dose 50 mg once daily. 

It has also been found that low doses of eplerenone (25-50 mg/d) may interfere with some of the fibrotic and inflammatory effects of aldosterone. By doing so, it can reduce the progression of albuminuria in diabetic patients. More important is that eplerenone has been found to reduce myocardial perfusion defects after myocardial infarction. In one clinical study, eplerenone reduced mortality rate by 15% (compared with placebo) in patients with mild to moderate heart failure after myocardial infarction. 

AMIODARONE POTASSIUM-SPARING DIURETICS Risk of T levels of eplerenone with amiodarone risk of hyperkalaemia directly related to serum levels Calcium channel blockers inhibit CYP3A4-mediated metabolism of eplerenone Restrict dose of eplerenone to 25mg/day. Monitor serum potassium concentrations closely watch for hyperkalaemia... 

Although troublesome, these adverse effects are reversible and dose-related. The advent of selective aldosterone receptor antagonists, such as eplerenone, should reduce these adverse effects and thereby improve patient compliance. In EPHESUS there was no increase in the incidence of gynecomastia, breast pain, or impotence in men or menstrual irregularities in women who took eplerenone. 

Like other diuretics, spironolactone should be initiated at a low dose and increased to treat symptoms. Spironolactone may be initiated at doses of 12.5 to 25 mg/day. Spironolactone shonld be avoided in severe renal failnre. Hyperkalemia and gynecomastia are the most common side effects. Eplerenone is a viable alternative to... 

Despite its improved selectivity, eplerenone has a relatively low affinity for MR in vitro (about 40-fold less potent compared to spironolactone [15]), and a lower potency and efficacy in a human hypertension study in comparison to spironolactone [16]. This study showed that 100 mg eplerenone given once daily or 50 mg twice daily have an efficacy of 50-75% compared to 50 mg spironolactone twice daily. This is important since the maximal approved daily dose of eplerenone for the treatment of hypertension is 100 mg in the US (eplerenone has no approval for this indication in Europe). 

These pharmacokinetic interactions are established. Although the clinical relevance has not been assessed, it is known that the risk of hyperkalaemia with eplerenone is related to its dose. Because the increase in the AUC of eplerenone with ketoconazole is so great, the manufacturers contraindicate this combination. They also contraindicate the concurrent use of other potent inhibitors of CYKA4, and they list clarithromycin, itraconazole, nefazodone, nelfmavir, ritonavir, telithromycin and trolean-domycin. ... 

In the UK, the manufacturers recommend that the dose of eplerenone should not exceed 25 mg daily in patients taking mild to moderate CYP3A4 inhibitors such as amiodarone, diltiazem, erythromycin, fluconazole, saquinavir and verapamil. In the US, the manufacturer recommends that the starting dose for hypertension should be reduced to 25 mg daily for patients taking these drugs. This seems a sensible precaution. However, note that in many cases erythromycin appears to be a more potent inhibitor of CYP3A4 than clarithromycin (and certainly the other moderate CYP3A4 inhibitors listed above), and so extra caution is probably warranted with this combination. 

Eplerenone did not alter the pharmacokinetics of warfarin to a clinically significant extent. However, in the UK the manufacturer still recommends caution when the warfarin dose is near the upper limit of the therapeutic range. ... 

Li JS, Flynn JT, Portman R, Davis I, Ogawa M, Shi H, Pressler ML. The efficacy and safety of the novel aldosterone antagonist eplerenone in children with hypertension a randomized, double-blind, dose-response study. J Pediatr 2010 157(2) 282-7. 

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