The Pharmacokinetics of the Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone

Finerenone, a selective and nonsteroidal antagonist of the mineralocorticoid receptor, has received regulatory approval with the indication of cardiorenal protection in patients with chronic kidney disease associated with type 2 diabetes. It is rapidly and completely absorbed and undergoes first-pass metabolism in the gut wall and liver resulting in a bioavailability of 43.5%. Finerenone can be taken with or without food. The pharmacokinetics of finerenone are linear and its half-life is 2 to 3 h in the dose range of up to 20 mg. Cytochrome P450 (CYP) 3A4 (90%) and CYP2C8 (10%) are involved in the extensive biotransformation of finerenone to pharmacologically inactive metabolites, which are excreted via both renal (80%) and biliary (20%) routes. Moderate or severe renal impairment, or moderate hepatic impairment result in area-under-the-curve increases of finerenone (< 40%), which do not require a dose adjustment per se, as the starting dose is based on estimated glomerular filtration rate (eGFR) and titrated according to serum potassium levels and eGFR decline. No relevant effects of age, sex, body size or ethnicity on systemic finerenone exposure were identified. Modulators of CYP3A4 activity were found to affect finerenone exposure, consistent with its classification as a sensitive CYP3A4 substrate. Serum potassium should be monitored during drug initiation or dosage adjustment of either a moderate or weak CYP3A4 inhibitor or finerenone, and the dose of finerenone should be adjusted as appropriate. Its use with strong inhibitors is contraindicated and strong or moderate inducers of CYP3A4 should be avoided. Finerenone has no potential to affect relevant CYP enzymes and drug transporters. Finerenone is a drug that is used to treat patients with chronic kidney disease and type 2 diabetes. Many of these patients take several medicines to treat other conditions. This review summarizes several studies showing the suitability of finerenone for these patients. Taken as a daily tablet, the dose circulates in the body before being quickly removed. The age, sex, body weight, and ethnicity of a patient do not affect dosing. As finerenone can cause an increase of serum potassium levels, potassium levels and kidney function should be measured before a patient starts treatment. The starting dose will depend on a patient’s kidney function, with the dose changed according to potassium levels and changes in kidney function. A protein called cytochrome P450 3A4 (CYP3A4) is key to removing finerenone from the body. Anyone taking medicines that strongly inhibit CYP3A4 should not take finerenone. Serum potassium levels should be measured before starting finerenone or changing the dose of either finerenone or ‘moderate’ or ‘weak’ CYP3A4 inhibitors, with the dose of finerenone adjusted as appropriate. Finerenone should not be taken alongside drugs that result in ‘moderate’ or ‘strong’ increases in CYP3A4 activity. In patients with moderate hepatic impairment, potassium should be monitored and finerenone doses be adjusted as appropriate. Finerenone is not expected to affect other drugs. Finerenone slows decline in kidney function, a treatment effect associated with reducing urine albumin. Potassium level-guided starting dose and dose changes support finerenone being effectively used and well tolerated in patients.