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Eplerenone

Pronunciation

Pronunciation

(e PLER en one)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Inspra: 25 mg, 50 mg

Generic: 25 mg, 50 mg

Brand Names: U.S.

  • Inspra

Pharmacologic Category

  • Antihypertensive
  • Diuretic, Potassium-Sparing
  • Mineralocorticoid (Aldosterone) Receptor Antagonists

Pharmacology

Aldosterone, a mineralocorticoid, increases blood pressure primarily by inducing sodium and water retention. Overexpression of aldosterone is thought to contribute to myocardial fibrosis (especially following myocardial infarction) and vascular fibrosis. Mineralocorticoid receptors are located in the kidney, heart, blood vessels, and brain. Eplerenone selectively blocks mineralocorticoid receptors reducing blood pressure in a dose-dependent manner and appears to prevent myocardial and vascular fibrosis.

Distribution

Vd: 42 to 90 L

Metabolism

Primarily hepatic via CYP3A4; metabolites inactive

Excretion

Urine (~67%); feces (~32%); <5% as unchanged drug in urine and feces

Time to Peak

Plasma: ~1.5 to 2 hours; may take up to 4 weeks for full antihypertensive effect

Half-Life Elimination

~3 to 6 hours

Protein Binding

~50%; primarily to alpha1-acid glycoproteins

Special Populations: Renal Function Impairment

AUC and Cmax increased 38% and 24%, respectively, in severe renal impairment and decreased by 26% and 3%, respectively, in hemodialysis.

Special Populations: Hepatic Function Impairment

Cmax and AUC increased 3.6% and 42%, respectively, in moderate hepatic impairment.

Special Populations: Elderly

Cmax and AUC increased 22% and 45%, respectively.

Special Populations: Race

Cmax and AUC decreased 19% and 25%, respectively, in black patients.

Use: Labeled Indications

Heart failure post-myocardial infarction (MI): Treatment of heart failure (HF) (LVEF ≤40%) following acute MI

Note: According to the Eighth Joint National Committee (JNC 8) guidelines, aldosterone antagonists are not recommended for the initial treatment of hypertension (James, 2013).

The ACCF/AHA 2013 heart failure guidelines recommend the use of aldosterone antagonists, along with other guideline directed medical therapies, to reduce morbidity and mortality in patients with an LVEF ≤40% following acute MI who develop symptoms of HF or have a history of diabetes mellitus (Yancy, 2013).

According to the 2013 ACCF/AHA guidelines for the management of ST-elevation myocardial infarction (STEMI) and the guidelines for the management of unstable angina/non-STEMI, an aldosterone antagonist should be given to patients who are already on an ACE inhibitor and beta-blocker, who have an LVEF ≤40% and either symptomatic HF or diabetes mellitus (ACCF/AHA [Anderson, 2013]; ACCF/AHA [O’Gara, 2013]).

Hypertension: Management of hypertension (monotherapy or in combination with other antihypertensive agents).

Note: According to the Eighth Joint National Committee (JNC 8) guidelines, aldosterone antagonists are not recommended for the initial treatment of hypertension (James, 2013).

Canadian labeling: Additional use (not in U.S. labeling): Heart failure: Treatment of NYHA class II chronic heart failure (HF) with left ventricular systolic dysfunction

Use: Unlabeled

The ACCF/AHA 2013 heart failure (HF) guidelines recommend the use of aldosterone antagonists, along with other guideline directed medical therapies, to reduce morbidity and mortality in patients with HF (NYHA class II-IV) with LVEF ≤35%. Patients with NYHA class II HF should have a history of prior cardiovascular hospitalization or elevated plasma natriuretic peptide levels to reduce morbidity and mortality (ACCF/AHA [Yancy, 2013]).

Contraindications

US labeling: Serum potassium >5.5 mEq/L at initiation; CrCl ≤30 mL/minute; concomitant use of strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir).

The following additional contraindications apply to patients with hypertension: Type 2 diabetes mellitus (noninsulin dependent, NIDDM) with microalbuminuria; serum creatinine >2.0 mg/dL in males or >1.8 mg/dL in females; CrCl <50 mL/minute; concomitant use with potassium supplements or potassium-sparing diuretics (eg, amiloride, spironolactone, triamterene).

Canadian labeling: Hypersensitivity to eplerenone or any component of the formulation; serum potassium >5 mEq/L at initiation; severe hepatic impairment (Child-Pugh class C); severe renal impairment (eGFR <30 mL/minute/1.73 m2); clinically significant hyperkalemia; concomitant use with potassium supplements, potassium-sparing diuretics or strong CYP3A4 inhibitors

The following additional contraindications apply to patients with hypertension: Type 2 diabetes mellitus (noninsulin dependent, NIDDM) with microalbuminuria; serum creatinine >1.5 mg/dL [132 micromole/L] in males or >1.3 mg/dL [115 micromole/L] in females; eGFR <50 mL/minute/1.73 m2

Dosing: Adult

Hypertension: Oral: Initial: 50 mg once daily; may increase to 50 mg twice daily if response is not adequate; may take up to 4 weeks for full therapeutic response. Doses >100 mg/day are not recommended due to increased risk of hyperkalemia and no greater therapeutic effect.

Dose modification during concurrent use with moderate CYP3A4 inhibitors: Initial: 25 mg once daily; may increase to 25 mg twice daily if response is not adequate (maximum: 50 mg/day).

Heart failure:

U.S. labeling:

Heart failure (post MI): Oral: Initial: 25 mg once daily; dosage goal: Titrate to 50 mg once daily within 4 weeks, as tolerated

Dosage adjustment per serum potassium concentrations for HF (post-MI):

<5 mEq/L:

Increase dose from 25 mg every other day to 25 mg once daily or

Increase dose from 25 mg once daily to 50 mg once daily

5 to 5.4 mEq/L: No adjustment needed

5.5 to 5.9 mEq/L:

Decrease dose from 50 mg once daily to 25 mg once daily or

Decrease dose from 25 mg once daily to 25 mg every other day or

Modify dose from 25 mg every other day to withhold medication

≥6 mEq/L: Withhold medication until potassium <5.5 mEq/L, then restart at 25 mg every other day

Alternatively, the ACCF/AHA 2013 HF guidelines recommend withholding treatment if potassium >5.5 mEq/L or renal function worsens; hold doses until potassium is <5 mEq/L and consider restarting with a reduced dose after confirming resolution of hyperkalemia/renal insufficiency for at least 72 hours (ACCF/AHA [Yancy, 2013]).

Dose modification during concurrent use with moderate CYP3A4 inhibitors: Initial: 25 mg once daily; maximum: 25 mg/day.

Heart failure (NYHA class II-IV with LVEF ≤35%) (off-label dose): Initial: 25 mg once daily; maximum: 50 mg/daily (ACCF/AHA [Yancy, 2013])

Canadian labeling:

Chronic HF (NYHA class II) or HF (post-MI): Oral:

eGFR ≥50 mL/minute/1.73 m2 and potassium ≤5 mEq/L: Initial: 25 mg once daily; may increase within 4 weeks as tolerated to a target dose of 50 mg once daily (maximum dose). Note: Treatment following MI should be initiated 3 to 14 days after MI.

Concurrent use with mild-to-moderate CYP3A4 inhibitors: Maximum dose: 25 mg once daily

eGFR 30 to 49 mL/minute/1.73 m2 and potassium ≤5 mEq/L: Initial: 25 mg every other day; may increase within 4 weeks as tolerated to a target dose of 25 mg once daily (maximum dose). Note: Treatment following MI should be initiated 3 to 14 days after MI.

Concurrent use with mild-to-moderate CYP3A4 inhibitors: Avoid concurrent use (target dose <25 mg once daily has not been studied).

Dosage adjustment (after initiation) per serum potassium concentrations:

<5 mEq/L:

Current dose is 25 mg every other day: Increase to 25 mg daily

Current dose is 25 mg daily and eGFR ≥50 mL/minute/1.73 m2 or not taking concurrent mild-to-moderate CYP3A4 inhibitor: Increase to 50 mg daily

Current dose is 25 mg daily and eGFR 30 to 49 mL/minute/1.73 m2 or if taking concurrent mild-to-moderate CYP3A4 inhibitor: Do not increase dose.

5 to 5.4 mEq/L: No adjustment needed

5.5 to 5.9 mEq/L:

Current dose is 50 mg daily: Decrease to 25 mg daily

Current dose is 25 mg daily: Decrease to 25 mg every other day

Current dose is 25 mg every other day: Withhold further doses; reinitiate only if potassium <5 mEq/L

≥6 mEq/L: Withhold further doses until potassium <5 mEq/L, then may temporarily resume therapy at 25 mg every other day (dose efficacy has not been established); reassess potassium levels in 1 week and if within acceptable limits, increase dose to 25 mg once daily; reassess potassium levels again in 1 week to determine whether therapy should be continued or interrupted.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

US labeling:

Hypertension:

CrCl ≥50 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling.

CrCl <50 mL/minute or serum creatinine >2 mg/dL (males) or >1.8 mg/dL (females): Use is contraindicated; risk of hyperkalemia increases with declining renal function.

Heart failure (post-MI):

CrCl >50 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling.

CrCl 31 to 50 mL/minute or serum creatinine >2 mg/dL (males) or >1.8 mg/dL (females): There are no dosage adjustment provided in the manufacturer’s labeling; use with caution.

CrCl ≤30 mL/minute: Use is contraindicated.

Heart failure (including post-MI) (ACCF/AHA [Yancy, 2013]:

eGFR ≥50 mL/minute/1.73 m2: Initial dose: 25 mg once daily; Maintenance dose (after 4 weeks of treatment and potassium ≤5 mEq/L): 50 mg once daily

eGFR 30 to 49 mL/minute/1.73 m2: Initial dose: 25 mg once every other day; Maintenance dose (after 4 weeks of treatment and potassium ≤5 mEq/L): 25 mg once daily

eGFR <30 mL/minute/1.73 m2: Not recommended

Hemodialysis: Not removed by hemodialysis.

Canadian labeling:

Hypertension:

eGFR ≥50 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer’s labeling; monitor serum potassium closely.

eGFR <50 mL/minute/1.73 m2 or serum creatinine >1.5 mg/dL [132 micromole/L] in males or >1.3 mg/dL [115 micromole/L] in females: Use is contraindicated.

Chronic HF (NYHA class II) or HF (post-MI):

eGFR ≥50 mL/minute/1.73 m2: No dosage adjustment necessary unless receiving concurrent mild-to-moderate CYP3A4 inhibitor, then maximum dose is 25 mg once daily.

eGFR 30 to 49 mL/minute/1.73 m2: Initial: 25 mg every other day; titrate to 25 mg once daily (maximum dose) within 4 weeks, as tolerated. Avoid concurrent use with mild-to-moderate CYP3A4 inhibitors.

eGFR ≤30 mL/minute/1.73 m2: Use is contraindicated.

Dosing: Hepatic Impairment

US labeling: There are no dosage adjustments provided in the manufacturer's labeling. Systemic exposure is increased in moderate hepatic impairment (Child-Pugh class B).

Canadian labeling:

Mild-to-moderate impairment: No dosage adjustment necessary.

Severe impairment: Use is contraindicated.

Administration

Oral: Administer with or without food.

Dietary Considerations

Do not use salt substitutes containing potassium.

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

ACE Inhibitors: Eplerenone may enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Ammonium Chloride: Potassium-Sparing Diuretics may enhance the adverse/toxic effect of Ammonium Chloride. Specifically the risk of systemic acidosis. Consider therapy modification

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Analgesics (Opioid): May enhance the adverse/toxic effect of Diuretics. Monitor therapy

Angiotensin II Receptor Blockers: Eplerenone may enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Canagliflozin: May enhance the hyperkalemic effect of Eplerenone. Canagliflozin may enhance the hypotensive effect of Eplerenone. Monitor therapy

Cardiac Glycosides: Potassium-Sparing Diuretics may diminish the therapeutic effect of Cardiac Glycosides. In particular, the inotropic effects of digoxin appear to be diminished. Potassium-Sparing Diuretics may increase the serum concentration of Cardiac Glycosides. This particular effect may be unique to Spironolactone. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

CycloSPORINE (Systemic): Eplerenone may enhance the hyperkalemic effect of CycloSPORINE (Systemic). Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Eplerenone. Management: When used concomitantly with moderate inhibitors of CYP3A4, eplerenone dosing recommendations vary by indication and international labeling. See full drug interaction monograph for details. Consider therapy modification

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Eplerenone. Avoid combination

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Drospirenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Fluconazole: May increase the serum concentration of Eplerenone. Management: Reduce the starting dose of eplerenone to 25 mg/day; monitor patients closely for increased eplerenone effects. Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Heparin: May enhance the hyperkalemic effect of Eplerenone. Monitor therapy

Heparin (Low Molecular Weight): May enhance the hyperkalemic effect of Eplerenone. Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Itraconazole: May increase the serum concentration of Eplerenone. Avoid combination

Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Ketoconazole (Systemic): May increase the serum concentration of Eplerenone. Avoid combination

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Lithium: Eplerenone may increase the serum concentration of Lithium. Monitor therapy

Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitrofurantoin: May enhance the hyperkalemic effect of Eplerenone. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Eplerenone. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Eplerenone. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Posaconazole: May increase the serum concentration of Eplerenone. Avoid combination

Potassium Salts: Eplerenone may enhance the hyperkalemic effect of Potassium Salts. Management: This combination is contraindicated in patients receiving eplerenone for treatment of hypertension. Consider therapy modification

Potassium-Sparing Diuretics: Eplerenone may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: This combination is contraindicated in patients receiving eplerenone for treatment of hypertension. Consider therapy modification

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

QuiNIDine: Potassium-Sparing Diuretics may diminish the therapeutic effect of QuiNIDine. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Sodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with diuretics, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, hydrate adequately and monitor fluid and renal status. Consider therapy modification

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tacrolimus (Systemic): Eplerenone may enhance the hyperkalemic effect of Tacrolimus (Systemic). Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Tolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy

Trimethoprim: May enhance the hyperkalemic effect of Eplerenone. Monitor therapy

Voriconazole: May increase the serum concentration of Eplerenone. Avoid combination

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Adverse Reactions

>10%: Endocrine & Metabolic: Hyperkalemia ([cardiac failure, post-myocardial infarction: >5.5 mEq/L: 16%; ≥6 mEq/L: 6%], [hypertension, >5.5 mEq/L: at dose of 400 mg: 9%; dose ≤200 mg: ≤1%]), hypertriglyceridemia (1% to 15%; dose-related)

1% to 10%:

Central Nervous System: Dizziness (3%), fatigue (2%)

Endocrine & Metabolic: Hyponatremia (2%; dose-related), albuminuria (1%), gynecomastia (≤1%), hypercholesterolemia (≤1%)

Gastrointestinal: Diarrhea (2%), abdominal pain (1%)

Genitourinary: Abnormal vaginal hemorrhage (≤2%), mastalgia (males: ≤1%)

Renal: Increased serum creatinine (cardiac failure, post-myocardial infarction: 6%)

Respiratory: Cough (2%), flu-like symptoms (2%)

<1% (Limited to important or life-threatening): Angioedema, increased blood urea nitrogen, increased liver enzymes, increased uric acid, skin rash

Warnings/Precautions

Concerns related to adverse effects:

• Hyperkalemia: Hyperkalemia may occur; risk of hyperkalemia is increased with renal impairment, proteinuria, diabetes, and patients taking concomitant ACE inhibitors, angiotensin-II blockers, NSAIDs, and/or moderate CYP3A inhibitors. Monitor closely for hyperkalemia; increases in serum potassium were dose related during clinical trials (ACCF/AHA [Yancy, 2013]). Dose reduction or interruption of therapy may be necessary with development of hyperkalemia. If concomitant moderate CYP3A inhibitor therapy cannot be avoided, reduce dose of eplerenone. Use is contraindicated in patients with potassium >5.5 mEq/L (US labeling) or >5 mEq/L (Canadian labeling) at initiation of therapy.

Disease-related concerns:

• Diabetes: Use with caution in patients with heart failure post-MI with diabetes (especially if patient has proteinuria); risk of hyperkalemia is increased.

• Heart failure: When evaluating a heart failure patient for eplerenone treatment, eGFR should be >30 mL/minute/1.73 m2 or creatinine should be ≤2.5 mg/dL (men) or ≤2 mg/dL (women) with no recent worsening and potassium <5 mEq/L with no history of severe hyperkalemia (ACCF/AHA [Yancy, 2013]). Serum potassium levels require close monitoring and management if elevated. The manufacturer recommends to withhold therapy if serum potassium >6 mEq/L. The ACCF/AHA recommends considering discontinuation upon the development of serum potassium >5.5 mEq/L or worsening renal function with careful evaluation of the entire medical regimen. Avoid routine triple therapy with the combined use of an ACE inhibitor, ARB, and eplerenone. Instruct patients with heart failure to discontinue use during an episode of diarrhea or dehydration or when loop diuretic therapy is interrupted (ACCF/AHA [Yancy, 2013]).

• Hepatic impairment: Use with caution in patients with moderate to severe hepatic impairment; Canadian labeling contraindicates use in severe hepatic impairment.

• Renal impairment: Risk of hyperkalemia is increased with declining renal function. Use with caution in patients with mild renal impairment; based on indication and degree of impairment use may be contraindicated (refer to contraindications field).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• Potassium supplements: Avoid potassium supplements, potassium-containing salt substitutes, a diet rich in potassium, or other drugs that can cause hyperkalemia (eg, other potassium-sparing diuretics, NSAIDS). Concomitant use of potassium supplements or potassium-sparing diuretics is contraindicated in the treatment of hypertension (U.S. labeling) or in all patients regardless of indication (Canadian labeling).

Monitoring Parameters

Blood pressure; serum potassium (prior to therapy, within the first week, 1 month after start of treatment or dose adjustment, then periodically as clinically indicated); additionally, check serum potassium and serum creatinine within 3 to 7 days after initiating concurrent therapy with moderate CYP3A4 inhibitor, ACE inhibitor, angiotensin-II blockers or NSAID.

ACCF/AHA heart failure guideline recommendations (ACCF/AHA [Yancy, 2013]): Serum potassium and renal function should be checked in 3 days after initiation, at 1 week after initiation, at least monthly for the first 3 months of therapy, and every 3 months thereafter. If adding or increasing the dose of concomitant ACE inhibitors or ARBs, a new cycle of monitoring should be done. If serum potassium increases to >5.5 mEq/L or renal function worsens, hold doses until potassium is <5 mEq/L and consider restarting with a reduced dose after confirming resolution of hyperkalemia/renal insufficiency for at least 72 hours.

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies. Information related to eplerenone use in pregnancy is limited (Cabassi, 2012; Morton, 2011). The use of mineralocorticoid receptor antagonists is not recommended to treat chronic uncomplicated hypertension in pregnant women and should generally be avoided in women of reproductive potential (ACOG, 2013).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber signs of high potassium (abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, numbness or tingling feeling), diarrhea, angina, tachycardia, urinary retention, change in the amount of urine produced, swelling of arms or legs, or vomiting (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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