General

Pronunciation:
e-ple-re-none

Trade Name(s)

• Inspra

Ther. Class.

antihypertensives

Pharm. Class.

aldosterone antagonists

Indications

• Hypertension (as monotherapy or in combination with other antihypertensive agents).
• Symptomatic HF with reduced ejection fraction (≤40%) after an acute MI.

Action

Blocks the effects of aldosterone by attaching to mineralocorticoid receptors.

Therapeutic Effect(s):

• Lowering of BP.
• Improved survival in patients with evidence of HF post-MI.

Pharmacokinetics

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Metabolism and Excretion: Primarily metabolized by the liver via the CYP3A isoenzyme; <5% excreted unchanged by the kidneys.

Half-life: 4–6 hr.

TIME/ACTION PROFILE (antihypertensive effect)

Contraindication/Precautions

Contraindicated in:

• Serum potassium >5.5 mEq/L;
• Type 2 diabetes with microalbuminuria (for patients with hypertension; ↑ risk of hyperkalemia);
• Serum creatinine >2 mg/dL in men or >1.8 mg/dL in women (for patients with hypertension);
• CCr ≤30 mL/min (for all patients); CCr <50 mL/min (for patients with hypertension);
• Concurrent use of potassium supplements or potassium-sparing diuretics (for patients with hypertension);
• Concurrent use of strong inhibitors of the CYP3A4 enzyme system;
• Lactation: Lactation.

Use Cautiously in:

• Moderate hepatic impairment;
• OB:  Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
• Pedi:  Safety and effectiveness not established in children;
• Geri:  ↑ risk of hyperkalemia in older adults due to age-related ↓ in renal function.

Adverse Reactions/Side Effects

Endo: gynecomastia

F and E: HYPERKALEMIA

GI: ↑ liver enzymes, abdominal pain, diarrhea

GU: abnormal vaginal bleeding, albuminuria

Metabolic: hypercholesterolemia, hypertriglyceridemia

Neuro: dizziness, fatigue

Misc: flu-like symptoms

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• Strong CYP3A inhibitors, including  ketoconazole,  itraconazole,  nefazodone,  clarithromycin,  ritonavir, or  nelfinavir, may ↑ levels and risk of toxicity; concurrent use contraindicated.
• Moderate CYP3A inhibitors, including  erythromycin,  fluconazole, or  verapamil, may ↑ levels and risk of toxicity; ↓ eplerenone dose.
•  NSAIDs  may ↓ antihypertensive effects.
•  ACE inhibitors  or  angiotensin II receptor blockers  may ↑ risk of hyperkalemia.

Route/Dosage

Hypertension

PO (Adults): 50 mg once daily initially; may ↑ to 50 mg twice daily;  Concurrent use of moderate CYP3A4 inhibitors (erythromycin, verapamil, or fluconazole):  25 mg once daily initially; may ↑ to 25 mg twice daily.

Heart Failure with Reduced Ejection Fraction Post–Myocardial Infarction

PO (Adults): 25 mg daily once initially; ↑ in 4 wk to 50 mg once daily;  Concurrent use of moderate CYP3A4 inhibitors (erythromycin, verapamil, or fluconazole):  Do not exceed 25 mg once daily.

Availability (generic available)

Tablets: 25 mg, 50 mg

Assessment

• Monitor BP periodically during therapy.

Lab Test Considerations:

May cause hyperkalemia. Monitor serum potassium before starting therapy, within the 1st wk, at 1 mo following start of therapy or dose adjustment, and periodically thereafter. Monitor serum potassium and serum creatinine in 3–7 days in patients who start taking a moderate CYP3A4 inhibitor.

• May ↓ serum sodium and ↑ serum triglyceride, cholesterol, ALT, GGT, creatinine, and uric acid levels.

Implementation

• Do not confuse Inspra with Spiriva.
• PO: Administer once daily with or without food.

Patient/Family Teaching

• Explain purpose and side effects of medication. Advise patient to read  Patient Information  before starting therapy. Instruct patient to take medication as directed at the same time each day, even if feeling well.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications. Inform patient not to use potassium supplements, salt substitutes containing potassium, or other Rx, OTC, or herbal products without consulting health care professional.
• Encourage patient to comply with additional interventions for hypertension (weight ↓, smoking cessation, moderation of alcohol consumption, regular exercise, stress management). Medication controls but does not cure hypertension.
• Instruct patient and caregiver on correct technique for monitoring BP. Advise them to monitor BP at least weekly, and notify health care professional of significant changes.
• May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• Advise patient to notify health care professional if dizziness, diarrhea, vomiting, rapid or irregular heartbeat, lower extremity edema, or difficulty breathing occur.
• Advise patient to inform health care professional of treatment regimen before treatment or surgery.
• Emphasize the importance of follow-up exams to check serum potassium.
• Rep:  Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy. May impair male fertility.

Evaluation/Desired Outcomes

• Lowering of BP.
• Improved survival in patients with evidence of HF post-MI.