Firialta Drug Interactions

Effects of other substances on finerenone: Finerenone is cleared almost exclusively via cytochrome P450 (CYP)-mediated oxidative metabolism (mainly CYP3A4 [90%] with a small contribution of CYP2C8 [10%]).
Effect of CYP3A4 inhibitors on finerenone: Strong CYP3A4 inhibitors on finerenone: Simulations suggest that concomitant use of Finerenone (Firialta) with itraconazole (200 mg BID), a strong CYP3A4 inhibitor, increases finerenone AUC (+ 531%) and C_max (+137%). Clarithromycin (500 mg BID), another strong inhibitor, also is predicted to increase finerenone AUC (+ 428%) and C_max (+ 125%). Due to an expected marked increase in finerenone exposure, concomitant use of Finerenone (Firialta) with itraconazole, clarithromycin and other strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, nelfinavir, cobicistat, telithromycin or nefazodone) is contraindicated (see Contraindications).
Moderate CYP3A4 inhibitors: Concomitant use of erythromycin (500 mg thrice daily), a moderate CYP3A4 inhibitor, increased finerenone mean AUC and C_max by 248% and 88%, respectively. Another moderate CYP3A4 inhibitor, verapamil (240 mg controlled-release tablet once daily), increased finerenone mean AUC and C_max by 170% and 120%, respectively. Serum potassium may increase, and therefore, monitoring of serum potassium is recommended (see Dosage & Administration and Precautions).
Weak CYP3A4 inhibitors: In an analysis of Finerenone (Firialta) in patients, the use of amiodarone, a weak CYP3A4 inhibitor, was estimated to result in a 21% increase of finerenone AUC. Simulations suggest that fluvoxamine (100 mg BID), another weak inhibitor, increases finerenone AUC (+57%) and C_max (+38%). Serum potassium may increase, and therefore, monitoring of serum potassium is recommended (see Dosage & Administration and Precautions).
Grapefruit: Concomitant intake of grapefruit or grapefruit juice is expected to increase the plasma concentration of finerenone and should be avoided (see Dosage & Administration and Precautions).
Effect of strong and moderate CYP3A4 inducers on finerenone: Simulations suggest that rifampicin (600 mg OD), a strong CYP3A4 inducer, decreases finerenone AUC (-93%) and C_max (-86%). Efavirenz (600 mg OD), a moderate CYP3A4 inducer, is predicted to decrease finerenone AUC (-81%) and C_max (-68%).
Concomitant use of Finerenone (Firialta) with rifampicin and other strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, phenobarbital, St John's Wort) or with efavirenz and other moderate CYP3A4 inducers, markedly decreases finerenone plasma concentration and results in reduced therapeutic effect and should be avoided (see Precautions).
Lack of clinically relevant drug-drug interaction: Concomitant use of gemfibrozil (600 mg twice daily), a strong inhibitor of CYP2C8, increased finerenone mean AUC and C_max by 10% and 16%, respectively. This is not clinically relevant.
Pre- and co-treatment with the proton pump inhibitor omeprazole (40 mg once daily) had no effect on finerenone mean AUC and mean C_max.
Concomitant use of antacid aluminum hydroxide and magnesium hydroxide (70 mVal) had no effect on finerenone mean AUC and reduced its mean C_max by 19%. This is not clinically relevant.
Effect of finerenone on other substances: In vivo a multiple-dose regimen of 20 mg finerenone once daily had no effect on the AUC of the CYP3A4 probe substrate midazolam. Finerenone neither inhibits nor induces CYP3A4.
A single dose of 20 mg finerenone also had no effect on AUC and C_max of the CYP2C8 probe substrate repaglinide. Finerenone does not inhibit CYP2C8.
Lack of mutual pharmacokinetic interaction was demonstrated between finerenone and the CYP2C9 substrate warfarin and between finerenone and the P-gp substrate digoxin.
Multiple doses of 40 mg finerenone once daily had no clinically relevant effect on AUC or C_max of the BCRP and OATP substrate rosuvastatin.
Pharmacodynamic interactions: Medications that increase serum potassium: It is anticipated that medications that increase serum potassium will increase the risk of hyperkalemia when used concomitantly with Finerenone (Firialta).
Concomitant use of Finerenone (Firialta) with the following medications should be avoided: potassium-sparing diuretics (e.g., amiloride, triamterene); other mineralocorticoid receptor antagonists (MRAs) (e.g., eplerenone, esaxerenone, spironolactone, canrenone).
Finerenone (Firialta) should be used with caution and serum potassium monitored when taken concomitantly with the following medications: potassium supplements; trimethoprim, or trimethoprim-sulfamethoxazole. Temporary discontinuation of Finerenone (Firialta) may be necessary. (See Precautions.)