Inspra Drug Interactions

Potassium-sparing diuretics: Eplerenone should not be administered to patients receiving potassium-sparing diuretics (see Contraindications and Hyperkalemia under Precautions).
ACE inhibitors, ARBs: The risk of hyperkalemia may increase when eplerenone is used in combination with an ACE inhibitor and/or an ARB. Close monitoring of serum potassium and renal function is recommended, especially in patients at risk for impaired renal function, e.g., the elderly.
Digoxin: No clinically significant drug-drug pharmacokinetic interactions have been found with digoxin. While a statistically significant 16% increase in AUC_0-24 was observed with digoxin 200 mcg and eplerenone 100 mg once daily in a pharmacokinetic study in healthy volunteers, this increase was not accompanied by clinical evidence of digoxin toxicity.
Warfarin: No clinically significant drug-drug pharmacodynamic interactions have been found with warfarin.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Drug interaction studies of eplerenone have not been conducted with NSAIDs. NSAIDs administered with potassium-sparing antihypertensives have been shown to result in hyperkalemia in patients with impaired renal function.
Lithium: Drug interaction studies of eplerenone have not been conducted with lithium. Lithium toxicity has been reported in patients receiving lithium concomitantly with diuretics and ACE inhibitors.
In vitro studies indicate that eplerenone is not an inhibitor of CYP1A2, CYP2C19, CYP2C9, CYP2D6 or CYP3A4 isozymes. Eplerenone is not a substrate or an inhibitor of P-glycoprotein.
CYP3A4 substrates: Results of pharmacokinetic studies with CYP3A4 probe-substrates, i.e. midazolam and cisapride, showed no significant pharmacokinetic interactions when these drugs were co-administered with eplerenone.
CYP3A4 inhibitors: Potent CYP3A4 inhibitors: Significant pharmacokinetic interactions may occur when eplerenone is co-administered with drugs that inhibit the CYP3A4 enzyme. A potent inhibitor of CYP3A4 (ketoconazole 200 mg twice daily) led to a 441% increase in AUC of eplerenone (see Contraindications). The concomitant use of eplerenone with potent CYP3A4 inhibitors such as ketoconazole, itraconazole, and ritonavir is contraindicated (see Contraindications).
Mild to moderate CYP3A4 inhibitors: Co-administration with erythromycin, saquinavir, verapamil, or fluconazole has led to significant pharmacokinetic interactions with rank order increases in AUC ranging from 98% to 187%. Eplerenone dosing should therefore not exceed 25 mg daily when mild to moderate inhibitors of CYP3A4 are co-administered with eplerenone (see Dosage & Administration).
CYP3A4 inducers: Co-administration of St. John's Wort (a potent CYP3A4 inducer) with eplerenone caused a 30% decrease in eplerenone AUC. A more pronounced decrease in eplerenone AUC may occur with more potent CYP3A4 inducers and the concomitant use of potent CYP3A4 inducers with eplerenone is not recommended (see Precautions).