Overview
11 DESCRIPTION INSPRA contains eplerenone, a blocker of aldosterone binding at the mineralocorticoid receptor. Eplerenone is chemically described as Pregn-4-ene-7,21-dicarboxylic acid, 9,11-epoxy-17-hydroxy-3-oxo-, γ-lactone, methyl ester, (7α,11α,17α)-. Its empirical formula is C 24 H 30 O 6 and it has a molecular weight of 414.50.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Eplerenone binds to the mineralocorticoid receptor and blocks the binding of aldosterone, a component of the renin-angiotensin-aldosterone-system (RAAS). Aldosterone synthesis, which occurs primarily in the adrenal gland, is modulated by multiple factors, including angiotensin II and non-RAAS mediators such as adrenocorticotropic hormone (ACTH) and potassium. Aldosterone binds to mineralocorticoid receptors in both epithelial (e.g., kidney) and nonepithelial (e.g., heart, blood vessels, and brain) tissues and increases blood pressure through induction of sodium reabsorption and possibly other mechanisms.
Indications
- 1 INDICATIONS AND USAGE INSPRA is an aldosterone antagonist indicated for: • Improving survival of stable adult patients with symptomatic heart failure with reduced ejection fraction (HFrEF) after an acute myocardial infarction. ( 1.1 ) • The treatment of hypertension in adults, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. ( 1.2 ) 1.
Common Doses
- 25 mg
- 50 mg
- 100 mg
Dosage
2 DOSAGE AND ADMINISTRATION HFrEF Post-MI: Initiate treatment with 25 mg once daily. Titrate to maximum of 50 mg once daily within 4 weeks, as tolerated. Dose adjustments may be required based on potassium levels. ( 2.1 ) Hypertension: 50 mg once daily, alone or combined with other antihypertensive agents. For inadequate response, increase to 50 mg twice daily. Higher dosages are not recommended. ( 2.2 ) For all patients: Measure serum potassium before starting INSPRA and periodically thereafter. ( 2.3 ) 2.
Contraindications
- 4 CONTRAINDICATIONS For All Patients INSPRA is contraindicated in all patients with: • serum potassium >5.5 mEq/L at initiation, • creatinine clearance ≤30 mL/min, or • 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 INSPRA is contraindicated for the treatment of hypertension in patients with: • type 2 diabetes with microalbuminuria, • serum creatinine >2.0 mg/dL in males or >1.
Side Effects
- 6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: • Hyperkalemia [see Warnings and Precautions (5.1) ] HFrEF Post-MI: Most common adverse reactions (>2% and more frequent than with placebo): hyperkalemia and increased creatinine. ( 6.1 ) Hypertension: In clinical studies, adverse reactions with INSPRA were uncommon. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Viatris at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.
Interactions
- 7 DRUG INTERACTIONS • CYP3A Inhibitors: In post-MI HFrEF patients, do not exceed 25 mg once daily when used with moderate CYP3A inhibitors (e.g., verapamil, erythromycin, saquinavir, fluconazole). In patients with hypertension, initiate at 25 mg once daily. For inadequate blood pressure response, dosing may be increased to a maximum of 25 mg twice daily. ( 2.4 , 7.1 , 12.3 ) 7.1 CYP3A Inhibitors Eplerenone metabolism is predominantly mediated via CYP3A. Do not use INSPRA with drugs that are strong inhibitors of CYP3A [see Contraindications (4) and Clinical Pharmacology (12.3) ] .