Eplerenone

EPLERENONE- eplerenone tablet
Eon Labs, Inc.

1 INDICATIONS AND USAGE

1.1 Heart Failure Post-Myocardial Infarction

Eplerenone tablets are indicated to improve survival of stable patients with symptomatic heart failure with reduced ejection fraction (≤40%) (HFrEF) after an acute myocardial infarction (MI).

1.2 Hypertension

Eplerenone tablets are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular (CV) events, primarily strokes and MI. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes.

Control of high blood pressure should be part of comprehensive CV risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).

Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce CV morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent CV outcome benefit has been a reduction in the risk of stroke, but reductions in MI and CV mortality also have been seen regularly.

Elevated systolic or diastolic pressure causes increased CV risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.

Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.

Eplerenone tablets may be used alone or in combination with other antihypertensive agents.

2 DOSAGE AND ADMINISTRATION

2.1 Heart Failure Post-Myocardial Infarction

Initiate treatment at 25 mg once daily and titrate to the recommended dose of 50 mg once daily, preferably within 4 weeks as tolerated by the patient.

Once treatment with eplerenone has begun, adjust the dose based on the serum potassium level as shown in Table 1.

Table 1. Dose Adjustment in Heart Failure Post-MI

Serum Potassium (mEq/L)	Dose Adjustment
<5.0	25 mg every other day to 25 mg once daily 25 mg once daily to 50 mg once daily
5.0 to 5.4	No adjustment
5.5 to 5.9	50 mg once daily to 25 mg once daily 25 mg once daily to 25 mg every other day 25 mg every other day to withhold
≥6.0	Withhold and restart at 25 mg every other day when potassium levels fall to ˂5.5 mEq/L

2.2 Hypertension

The recommended starting dose of eplerenone is 50 mg administered once daily. The full therapeutic effect of eplerenone is apparent within 4 weeks. For patients with an inadequate blood pressure response to 50 mg once daily increase the dosage of eplerenone to 50 mg twice daily. Higher dosages of eplerenone are not recommended because they have no greater effect on blood pressure than 100 mg and are associated with an increased risk of hyperkalemia [see Clinical Studies (14.2)].

2.3 Recommended Monitoring

Measure serum potassium before initiating eplerenone therapy, within the first week, and at one month after the start of treatment or dose adjustment. Assess serum potassium periodically thereafter.

Check serum potassium and serum creatinine within 3 to 7 days of a patient initiating a moderate CYP3A inhibitor ACE inhibitors, angiotensin-II blockers or non-steroidal-anti-inflammatories.

2.4 Dose Modifications for Use With Moderate CYP3A Inhibitors

In post-MI HFrEF patients receiving a moderate CYP3A inhibitor (e.g., erythromycin, saquinavir, verapamil, and fluconazole), do not exceed 25 mg once daily. In patients with hypertension receiving a moderate CYP3A inhibitor, initiate at 25 mg once daily. For inadequate blood pressure response, dosing may be increased to a maximum of 25 mg twice daily [see Drug Interactions (7.1)].

3 DOSAGE FORMS AND STRENGTHS

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25 mg tablets: round, white, film-coated tablets debossed with “SZ” on one side and “12” on the other.

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50 mg tablets: round, yellow, film-coated tablets debossed with “SZ” on one side and “16” on the other.

4 CONTRAINDICATIONS

For All Patients

Eplerenone is contraindicated in all patients with:

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serum potassium >5.5 mEq/L at initiation,

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creatinine clearance ≤30 mL/min, or

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concomitant administration of strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, and nelfinavir) [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].

For Patients Treated for Hypertension

Eplerenone is contraindicated for the treatment of hypertension in patients with:

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type 2 diabetes with microalbuminuria,

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serum creatinine >2.0 mg/dL in males or >1.8 mg/dL in females,

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creatinine clearance <50 mL/min, or

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concomitant administration of potassium supplements or potassium-sparing diuretics (e.g., amiloride, spironolactone, or triamterene) [see Warnings and Precautions (5.1), Adverse Reactions (6.2), Drug Interactions (7), and Clinical Pharmacology (12.3)].

5 WARNINGS AND PRECAUTIONS