Epistemis

Finerenone

  • Selective Nonsteroidal Antagonist of the Mineralocorticoid Receptor

Common trade names: Kerendia.

Mechanism

Pharmacological Group

Third-generation non-steroidal selective mineralocorticoid receptor antagonist (MRA).

Mechanism of Action

Unlike spironolactone and eplerenone, finerenone is a non-steroidal blocker that is highly selective and potent of the Mineralocorticoid Receptor (MR). It binds to the receptor with a bulky and rigid molecular character, which mechanically blocks the recruitment of inflammatory and profibrotic transcription coactivators to the cell nucleus. It presents a balanced tissue distribution between the kidney and the heart. This reduces the progression of kidney disease by directly attenuating inflammatory damage and fibrosis in the glomeruli and renal tubules.

Pharmacokinetics

Key Pharmacokinetics

  • Bioavailability: 44% (due to moderate first pass clearance).
  • Protein binding: High (~92%), mainly to plasma albumin.
  • Metabolism: Metabolized almost entirely in the liver at the level of cytochrome CYP3A4 (90%) and to a lesser extent by CYP2C8. Its metabolites are inactive.
  • Excretion: 80% excreted through the urine in the form of metabolites; 20% fecally.
  • Half-life: 2 to 3 hours.

Indicators and dose

Clinical Indications

  • Chronic Kidney Disease associated with Type 2 Diabetes: Indicated to reduce the risk of sustained reduction in glomerular filtration rate, end-stage renal disease, cardiovascular death and non-fatal myocardial infarction (pivotal clinical studies FIDELIO-DKD and FIGARO-DKD).

Dosage and Settings

  • Starting dose: It depends strictly on the patient's basal glomerular filtration rate:
    - eGFR 60 mL/min/1.73m2: 20 mg orally once a day.
    - eGFR 25 to 60 mL/min/1.73m2: 10 mg orally once a day.
    - eGFR < 25 mL/min/1.73m2: Initiating treatment is not recommended due to the paucity of clinical data.
  • Titration: Adjust after 4 weeks according to serum potassium levels (maintain if K+ ≤ 4.8 mEq/L; temporarily suspend if K+ > 5.5 mEq/L).

Security

Contraindications

  • Absolute: Primary adrenal insufficiency (Addison's Disease); concomitant severe hyperkalemia; coadministration with strong CYP3A4 inhibitors.

Adverse Effects (ADR)

  • Very common: Hyperkalemia (however, studies demonstrated a significantly lower rate of discontinuation of therapy for hyperkalemia compared to spironolactone and eplerenone).
  • Common: Transient arterial hypotension, moderate hyponatremia, transient pruritus.

Interactions

  • Moderate and Potent CYP3A4 Inhibitors (e.g. Erythromycin, Verapamil, Itraconazole, grapefruit juice): Drastically increase plasma exposure to finerenone, requiring strict monitoring of potassium or direct contraindication to concomitant use.
  • ACEI / ARA-II / Sacubitril-Valsartan: Pharmacodynamic synergism on plasma potassium levels.

Pregnancy and Breastfeeding

Category D / Contraindicated. Animal data demonstrate clear embryonic and fetal toxicity. The use of effective contraception is recommended during treatment. You should not breastfeed.

Epistemis is educational review material. It is not a medical device, does not diagnose or prescribe treatment, and does not replace formal medical training, current clinical guidelines, or professional clinical judgment.

PreviousEplerenone
System
Renal and Diuretics
Cluster
Selective Nonsteroidal Antagonist of the Mineralocorticoid…
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