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Therapeutic Classification: antihypertensives

Pharmacologic Classification: aldosterone antagonists

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

• Blocks the effects of aldosterone by attaching to mineralocorticoid receptors.

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

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

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

Half-life: 4–6 hr.

(antihypertensive effect)

Contraindicated in:

• Serum potassium >5.5 mEq/L
• Type 2 diabetes with microalbuminuria (for patients with HTN; ↑ risk of hyperkalemia)
• Serum creatinine >2 mg/dL in males or >1.8 mg/dL in females (for patients with HTN)
• CCr 30 mL/min (for all patients); CCr <50 mL/min (for patients with HTN)
• Concurrent use of potassium supplements or potassium-sparing diuretics (for patients with HTN)
• 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.

Endo: gynecomastia.

F and E: HYPERKALEMIA.

GI: ↑liver enzymes, abdominal pain, diarrhea.

GU: abnormal vaginal bleeding, albuminuria.

Metab: hypercholesterolemia, hypertriglyceridemia.

Neuro: dizziness, fatigue.
Misc: flu-like symptoms.

Drug-Drug:

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

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.

(Generic available)

• Tablets: 25 mg; 50 mg;

• Monitor BP periodically during therapy.
• Monitor prescription refills to determine adherence.

• May cause hyperkalemia. Monitor serum potassium levels prior to starting therapy, within the first 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 cause ↓ serum sodium and ↑ serum triglyceride, cholesterol, ALT, GGT, creatinine, and uric acid levels.

• Do not confuse Inspra with Spiriva.
• PO: Administer once daily. May be increased to twice daily if response is inadequate.

• Instruct patient to take medication as directed at the same time each day, even if feeling well.
• Encourage patient to comply with additional interventions for HTN (weight reduction, discontinuation of smoking, moderation of alcohol consumption, regular exercise, stress management). Medication controls but does not cure HTN.
• Instruct patient and family on correct technique for monitoring BP. Advise them to monitor BP at least weekly, and notify health care professional of significant changes.
• Inform patient not to use potassium supplements, salt substitutes containing potassium, or other Rx, OTC, or herbal products without consulting health care professional.
• 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 prior to treatment or surgery.
• Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected. Advise patient to avoid breastfeeding during therapy. May impair male fertility.
• Emphasize the importance of follow-up exams to check serum potassium.

• Decrease in BP without appearance of side effects.
• Improvement in survival in patients with evidence of HF post-MI.

Inspra