EPLERENONE Drug Interactions: What You Need to Know

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 eplerenone tablets with drugs that are strong inhibitors of CYP3A <span class="opacity-50 text-xs">[see Contraindications (4) and Clinical Pharmacology (12.3) ]</span>. In post-MI HFrEF patients taking a moderate CYP3A inhibitor, do not exceed 25 mg once daily. In patients with hypertension taking a moderate CYP3A inhibitor, initiate at 25 mg once daily. For inadequate blood pressure response, dosing may be increased to a maximum of 25 mg twice daily <span class="opacity-50 text-xs">[see Dosage and Administration (2.3, 2.4) and Clinical Pharmacology (12.3) ]</span>.

7.2 ACE Inhibitors and Angiotensin II Receptor Antagonists The risk of hyperkalemia increases when eplerenone is used in combination with an ACE inhibitor and/or an ARB. A close monitoring of serum potassium and renal function is recommended, especially in patients at risk for impaired renal function, e.g., the elderly <span class="opacity-50 text-xs">[see Warnings and Precautions (5.1) ]</span>.

7.3 Lithium A drug interaction study of eplerenone with lithium has not been conducted. Lithium toxicity has been reported in patients receiving lithium concomitantly with diuretics and ACE inhibitors. Serum lithium levels should be monitored frequently if eplerenone tablets is administered concomitantly with lithium.

7.4 Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) A drug interaction study of eplerenone with an NSAID has not been conducted. The administration of other potassium-sparing antihypertensives with NSAIDs has been shown to reduce the antihypertensive effect in some patients and result in severe hyperkalemia in patients with impaired renal function. Therefore, when eplerenone tablets and NSAIDs are used concomitantly, monitor blood pressure and serum potassium levels.

For all patients:

• Serum potassium greater than 5.5 mEq/L at initiation ( 4 )
• Creatinine clearance less than or equal to 30 mL/min ( 4 )
• Concomitant use with strong CYP3A inhibitors ( 4 , 7.1 ) For the treatment of hypertension:
• Type 2 diabetes with microalbuminuria ( 4 )
• Serum creatinine greater than 2.0 mg/dL in males, greater than 1.8 mg/dL in females ( 4 )
• Creatinine clearance less than 50 mL/min ( 4 )
• Concomitant use of potassium supplements or potassium-sparing diuretics ( 4 ) For all patients: Eplerenone is contraindicated in all patients with:
• serum potassium greater than 5.5 mEq/L at initiation,
• creatinine clearance less than or equal to 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 Eplerenone is contraindicated for the treatment of hypertension in patients with:
• type 2 diabetes with microalbuminuria,
• serum creatinine greater than 2.0 mg/dL in males or greater than 1.8 mg/dL in females,
• creatinine clearance less than 50 mL/min, or
• concomitant administration of potassium supplements or potassium-sparing diuretics (e.g., amiloride, spironolactone, or triamterene) [see WARNINGS AND PRECAUTIONS (5.1) , ADVERSE REACTIONS (6.2) , DRUG INTERACTIONS (7) , and CLINICAL PHARMACOLOGY (12.3) ].

AND PRECAUTIONS

• Hyperkalemia : Patients with decreased renal function, diabetes, proteinuria or patients who are taking ACEs and ARBs, NSAIDs or moderate CYP3A inhibitors are at increased risk. Monitor serum potassium levels and adjust dose as needed. ( 5.1 )

5.1 Hyperkalemia The risk of hyperkalemia is higher in patients with impaired renal function, proteinuria, diabetes and those concomitantly treated with ACEs, ARBs, NSAIDs and moderate CYP3A inhibitors. Minimize the risk of hyperkalemia with proper patient selection and monitoring <span class="opacity-50 text-xs">[see Dosage and Administration (2.1) , Contraindications (4) , Adverse Reactions (6.2) , and Drug Interactions (7) ]</span> . Monitor patients for the development of hyperkalemia until the effect of eplerenone tablets is established. Patients who develop hyperkalemia (5.5 to 5.9 mEq/L) may continue eplerenone tablets therapy with proper dose adjustment. Dose reduction decreases potassium levels. Patients on moderate CYP3A inhibitors that cannot be avoided should have their dose of eplerenone reduced <span class="opacity-50 text-xs">[see Drug Interactions (7.2) ]</span>.