Finerenone

Usage

Finerenone is prescribed to reduce the risk of:

• Sustained estimated glomerular filtration rate (eGFR) decline
• End-stage kidney disease (ESKD)
• Cardiovascular death
• Non-fatal myocardial infarction
• Hospitalization for heart failure

It is used in adults with chronic kidney disease (CKD) associated with type 2 diabetes (T2D).

Pharmacological Classification: Non-steroidal mineralocorticoid receptor antagonist (MRA).

Mechanism of Action: Finerenone blocks the mineralocorticoid receptor (MR), which is activated by aldosterone. Overactivation of the MR pathway contributes to inflammation and fibrosis in the kidneys and heart. By blocking MR, finerenone helps to protect these organs in patients with CKD and T2D.

Alternate Names

No alternate generic names are listed.

Brand Names: Kerendia.

How It Works

Pharmacodynamics: Finerenone selectively antagonizes the mineralocorticoid receptor (MR). In patients with CKD and T2D, this reduces the progression of kidney damage and lowers the risk of cardiovascular events.

Pharmacokinetics:

• Absorption: Finerenone is absorbed orally, with or without food. However, it should not be taken with grapefruit or grapefruit juice.
• Metabolism: Primarily metabolized by CYP3A4.
• Elimination: Primarily eliminated via hepatic metabolism and biliary/fecal excretion, with a small contribution via renal excretion.

Mode of Action: Finerenone competitively binds to the mineralocorticoid receptor (MR), thereby blocking the binding of aldosterone and preventing MR activation.

Receptor Binding: Mineralocorticoid receptor (MR).

Enzyme Inhibition/Neurotransmitter Modulation: No significant direct enzyme inhibition or neurotransmitter modulation. However, its metabolism is affected by CYP3A4 inducers and inhibitors.

Elimination Pathways: Primarily hepatic metabolism and biliary/fecal excretion, with a small fraction of renal excretion.

Dosage

Standard Dosage

Adults:

• Initial Dosage: Based on eGFR:
  • eGFR ≥ 60 mL/min/1.73 m²: 20 mg orally once daily
  • eGFR 25 to < 60 mL/min/1.73 m²: 10 mg orally once daily
  • eGFR < 25 mL/min/1.73 m²: Not recommended
• Target Dose: 20 mg orally once daily (after 4 weeks based on serum potassium and eGFR).
• Maximum Dose: 20 mg orally once daily.

Children: Safety and efficacy not established.

Special Cases:

• Elderly Patients: No dosage adjustment required.

• Patients with Renal Impairment: Dose adjustments and initiation are based on eGFR; not recommended if eGFR < 25 mL/min/1.73 m².

• Patients with Hepatic Dysfunction:

  • Mild or moderate (Child-Pugh A or B): No adjustment needed.
  • Severe (Child-Pugh C): Avoid.

• Patients with Comorbid Conditions: Close monitoring of serum potassium is essential, particularly in patients with diabetes, cardiovascular disease, or other conditions predisposing to hyperkalemia.

Clinical Use Cases

Finerenone is not indicated for use in situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its use is specific to managing CKD in patients with type 2 diabetes to reduce long-term risks.

Dosage Adjustments

Dosage adjustments are based primarily on serum potassium levels and eGFR. See the table under “Standard Dosage - Adults” for initial and target dosing. Regular monitoring of serum potassium and eGFR is necessary for ongoing dose adjustments.

Side Effects

Common Side Effects

• Hyperkalemia
• Hypotension
• Hyponatremia

Rare but Serious Side Effects

• Severe hyperkalemia (requiring urgent medical intervention)
• Angioedema (allergic reaction)

Long-Term Effects

Potential long-term effects are primarily related to hyperkalemia if not properly managed.

Adverse Drug Reactions (ADR)

Severe hyperkalemia is the most important ADR requiring immediate intervention.

Contraindications

• Concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir, clarithromycin).
• Adrenal insufficiency.
• Hypersensitivity to finerenone.

Drug Interactions

• Strong CYP3A4 inhibitors: Contraindicated (increase finerenone levels).
• Moderate CYP3A4 inhibitors: Dose adjustment may be necessary. Monitor serum potassium.
• CYP3A4 inducers: May decrease finerenone levels.
• Potassium-sparing diuretics, MRAs: Increased risk of hyperkalemia. Use with caution. Monitor serum potassium closely.
• Potassium supplements, trimethoprim: Increased risk of hyperkalemia. Use with caution. Monitor serum potassium closely.

Pregnancy and Breastfeeding

• Pregnancy: Not recommended unless clearly needed. Potential for fetal harm. Effective contraception is advised.
• Breastfeeding: Not recommended. It is unknown if finerenone is excreted in human milk.

Drug Profile Summary

• Mechanism of Action: Selective mineralocorticoid receptor antagonist.
• Side Effects: Hyperkalemia, hypotension, hyponatremia.
• Contraindications: Strong CYP3A4 inhibitors, adrenal insufficiency.
• Drug Interactions: Multiple drug interactions, especially with CYP3A4 modulators and potassium-affecting drugs.
• Pregnancy & Breastfeeding: Not recommended.
• Dosage: Initial and target dosages are based on renal function; maximum 20 mg once daily.
• Monitoring Parameters: Serum potassium, eGFR, blood pressure.

Popular Combinations

Finerenone is typically used in conjunction with standard of care therapies for CKD and T2D, including angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). These drugs often have synergistic effects and can be used with finerenone in maximum tolerated labelled doses. SGLT2 inhibitors are frequently also prescribed.

Precautions

• Monitor serum potassium and eGFR regularly.
• Caution in patients with a history of hyperkalemia or with risk factors for hyperkalemia (e.g., impaired renal function).
• Avoid grapefruit and grapefruit juice.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Finerenone?

A: The initial dosage is 10 mg or 20 mg once daily, depending on eGFR. The target dose is 20 mg once daily after 4 weeks based on serum potassium and eGFR.

Q2: What is the mechanism of action of Finerenone?

A: Finerenone is a selective mineralocorticoid receptor antagonist. It blocks the activation of this receptor by aldosterone, which in turn helps to reduce inflammation and fibrosis in the kidneys and cardiovascular system.

Q3: What are the most common side effects of Finerenone?

A: Hyperkalemia, hypotension, and hyponatremia.

Q4: Is Finerenone safe in pregnancy?

A: Finerenone is not recommended during pregnancy unless clearly needed. There is a potential risk to the fetus.

Q5: Can Finerenone be used in patients with severe hepatic impairment?

A: No, Finerenone is contraindicated in patients with severe hepatic impairment (Child-Pugh C).

Q6: What are the key drug interactions with Finerenone?

A: Finerenone has significant interactions with strong CYP3A4 inhibitors (contraindicated), moderate CYP3A4 inhibitors (dose adjustment needed), and potassium-sparing diuretics or other MRAs (risk of hyperkalemia).

Q7: How should Finerenone be taken?

A: Finerenone tablets should be taken orally once daily, with or without food, but not with grapefruit or grapefruit juice.

Q8: When should serum potassium be monitored in patients taking Finerenone?

A: Serum potassium should be measured before starting treatment, 4 weeks after initiation or dose adjustment, and periodically throughout treatment as needed.

Q9: What should I do if a patient on Finerenone develops hyperkalemia?

A: If serum potassium exceeds 5.5 mEq/L, withhold finerenone and restart at a lower dose (10 mg once daily) only when serum potassium levels are 5.0 mEq/L or less. Follow established guidelines for managing hyperkalemia.

Q10: Can patients crush Finerenone tablets?

A: Yes, for patients who cannot swallow whole tablets, Kerendia tablets can be crushed and mixed with water or soft foods immediately before administration.