EPLERENONE

EPLERENONE (e-ple're-none) Inspra Classifications: electrolye & water balance agent; selective aldosterone receptor antagonist (sara); antihypertensive; Therapeutic: antihypertensive; diuretic; sara Pregnancy Category: Spironolactone B

Availability

25 mg, 50 mg, 100 mg tablets

Action

Binds to mineralocorticoid receptors and blocks the binding of aldosterone, a component of the renin-angiotensin-aldosterone system (RAAS). Thus eplerenone blocks the primary effect of aldosterone which is sodium reabsorption.

Therapeutic Effect

Lowers blood pressure by inhibiting sodium and water retention, thus reducing total plasma volume.

Uses

Treatment of hypertension, alone or with other antihypertensive agents. Adjunctive therapy for post MI heart failure.

Contraindications

Serum potassium >5.5 mEq/L; type 2 diabetes with microalbuminuria; serum creatinine >2.0 mg/dL in males or >1.8 mg/dL in females; creatinine clearance <50 mL/min; concomitant treatment with potassium supplements or potassium-sparing diuretics (amiloride, spironolactone, or triamterene), or strong inhibitors of CYP450 3A4 (e.g., ketoconazole, itraconazole); lactation.

Cautious Use

Hepatic impairment; concomitant use of another mineralocorticoid receptor blocker and ACE inhibitors or angiotensin II antagonists; severe hepatic disease; concomitant treatment with moderate inhibitors of CYP450 3A4 (e.g., fluconazole, erythromycin, verapamil, saquinavir); pregnancy (category B); safety and efficacy in children, infants, or neonates are not established.

Route & Dosage

Hypertension Adult: PO 50 mg once daily, may be increased to 50 mg b.i.d. or 100 mg q.d., if inadequate response after 4 wk Renal Impairment Do not administer if Clcr <50 mL/min due to risk of hyperkalemia.

Administration

Oral

• Do not administer in combination with potassium supplements or potassium-sparing diuretics.
• Manufacturer recommends dosage reduction to 25 mg once daily with concurrent administration of erythromycin, saquinavir, verapamil, or fluconazole.
• Store at 15°–30° C (59°–86° F).

Adverse Effects (≥1%)

Body as a Whole: Fatigue, flu-like syndrome. CNS: Headache, dizziness. CV: Angina, MI. GI: Diarrhea, abdominal pain. Endocrine: Gynecomastia. Metabolic: Hyperkalemia, increased GGT, hypercholesterolemia, hypertriglyceridemia, decreased sodium levels. Respiratory: Cough. Urogenital: Albuminuria, abnormal vaginal bleeding.

Interactions

Drug: ace inhibitors, angiotensin ii receptor blockers, azole antifungals (e.g., fluconazole, itraconazole, ketoconazole), erythromycin, saquinavir, verapamil may increase risk of hyperkalemia. Food: Potassium-containing salt substitutes may increase risk of hyperkalemia.

Pharmacokinetics

Absorption: Rapidly absorbed. Peak: 1.5 h. Distribution: 50% protein bound, primarily to alpha₁-acid glycoproteins. Metabolism: In liver by CYP3A4. Elimination: 32% in feces, 67% in urine. Half-Life: 4–6 h.

Nursing Implications

Assessment & Drug Effects

• Monitor cardiovascular status with frequent BP determinations. Note that BP lowering usually occurs within 2 wk with maximal antihypertensive effects achieved within 4 wk.
• Lab tests: Monitor baseline and periodic serum potassium, serum sodium, renal function tests, lipid profile, and LFTs. Monitor type 2 diabetics for microalbuminuria.
• Concurrent drugs: Monitor serum potassium levels more frequently when patient also receiving an ACE inhibitor or an angiontensin II receptor antagonist. Monitor frequently for lithium toxicity with concurrent use.
• Withhold drug and notify physician for any of the following: serum potassium >5.5 mEq/L, serum creatinine >2.0 mg/dL in males or >1.8 mg/dL in females, creatinine clearance <50 mL/min, microalbuminuria in type 2 diabetics.

Patient & Family Education

• Do not use potassium supplements, salt substitutes containing potassium, or contraindicated drugs (e.g., ketoconazole, itraconazole) without consulting physician.
• Do not use OTC nonsteroidal anti-inflammatory drugs without consulting physician.
• Do not drive or operate machinery until reaction to drug is known. It may cause dizziness.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug