Finerenone 20 mg · Tablets

Finerenone is a nonsteroidal, selective antagonist of the mineralocorticoid receptor (MR), which is activated by aldosterone and cortisol and regulates gene transcription. Finerenone blocks MR mediated sodium reabsorption and MR overactivation in both epithelial (e.g., kidney) and nonepithelial (e.g., heart, and blood vessels) tissues. MR overactivation is thought to contribute to fibrosis and inflammation. Finerenone has a high potency and selectivity for the MR and has no relevant affinity for androgen, progesterone, estrogen, and glucocorticoid receptors.

Finerenone exposure increased proportionally over a dose range of 1.25 to 80 mg (0.06 to 4 times the maximum approved recommended dosage). Steady state of finerenone was achieved after 2 days of dosing. The estimated steady-state geometric mean Cmax,md was 166 µg/L and steady-state geometric mean AUCτ,md was 718 µg.h/L following administration of finerenone 20 mg to patients.

Absorption — Finerenone is completely absorbed after oral administration but undergoes metabolism resulting in absolute bioavailability of 44%. Finerenone Cmax was achieved between 0.5 and 1.25 hours after dosing.

Effect of Food — There was no clinically significant effect on finerenone AUC following administration with high fat, high calorie food.

Distribution — The volume of distribution at steady-state (Vss) of finerenone is 52.6 L. Plasma protein binding of finerenone is 92%, primarily to serum albumin, in vitro.

Elimination — The terminal half-life of finerenone is about 2 to 3 hours, and the systemic blood clearance is about 25 L/h.

Metabolism — Finerenone is primarily metabolized by CYP3A4 (90%) and to a lesser extent by CYP2C8 (10%) to inactive metabolites.

Excretion — About 80% of the administered dose is excreted in urine (<1% as unchanged) and approximately 20% in feces (< 0.2% as unchanged).

Specific Populations — There are no clinically significant effects of age (18 to 86 years), sex, race/ethnicity (White, Asian, Black, and Hispanic), or weight (54 to 126 kg) on the pharmacokinetics of finerenone.

Renal Impairment — There were no clinically relevant differences in finerenone AUC or Cmax values in patients with eGFR 15 to < 90 mL/min/1.73m2 compared to eGFR ≥ 90 mL/min/1.73m2. For dosing recommendations based on eGFR and serum potassium levels [see Dosage and Administration (2)].

Hepatic Impairment — There was no clinically significant effect on finerenone exposure in cirrhotic patients with mild hepatic impairment (Child Pugh A).

Finerenone mean AUC was increased by 38% and Cmax was unchanged in cirrhotic patients with moderate hepatic impairment (Child Pugh B) compared to healthy control subjects.

The effect of severe hepatic impairment (Child Pugh C) on finerenone exposure was not studied.