FIRIALTA 10 MG TABLET

Indications

• Chronic kidney disease (stage 3 and 4 with albuminuria) associated with type 2 diabetes

Dosage

Adults: Initially, 10 mg once daily, increased to 20 mg once daily if necessary, depending on serum potassium levels and estimated GFR.

Mechanism of action

Finerenone selectively binds to mineralocorticoid receptors (MR), preventing the binding of aldosterone. This action inhibits the receptor's activation, which is normally responsible for pro-inflammatory and pro-fibrotic gene transcription. By blocking this pathway, finerenone reduces inflammation, fibrosis, and sodium reabsorption, thereby lowering the risk of renal and cardiovascular complications in patients with chronic kidney disease and type 2 diabetes.

Pharmacodynamics

Finerenone demonstrates a moderate duration of action and a wide therapeutic window, making it suitable for once-daily administration. Clinical trial data indicate that it effectively reduces the risk of sustained decline in glomerular filtration rate (GFR), end-stage kidney disease, and cardiovascular events such as death, heart attacks, and hospitalizations due to heart failure. It is essential to monitor potassium levels due to the risk of hyperkalemia associated with its use.

Pharmacokinetics

Finerenone is absorbed after oral administration, with peak plasma concentrations typically achieved within 1 to 4 hours. It undergoes extensive hepatic metabolism primarily via CYP3A4. The elimination half-life is approximately 2 to 3 hours, allowing for once-daily dosing. Excretion occurs mainly through feces, with renal elimination being minimal. Patients with renal impairment may require careful monitoring and dose adjustments based on potassium levels and renal function.

Contra-indications

• Addison's disease
• Hyperkalaemia

Adverse effects

• Electrolyte imbalance
• Hypotension
• Pruritus

Interactions

• Cobicistat increases exposure to finerenone
• Dabrafenib decreases exposure to finerenone
• Bosentan decreases exposure to finerenone
• Idelalisib increases exposure to finerenone
• Clarithromycin increases exposure to finerenone
• St. John's Wort decreases exposure to finerenone
• Rifampicin decreases exposure to finerenone
• Dronedarone increases exposure to finerenone (unknown)
• Antifungals (azoles) increase exposure to finerenone (unknown)
• Crizotinib increases exposure to finerenone (unknown)

Precautions

• Reassess serum potassium periodically
• Monitor renal function in patients with renal impairment
• Consider dose adjustments based on serum potassium levels

Pregnancy

Avoid unless potential benefit outweighs risk; reproductive toxicity has been seen in animal studies.

Breast-feeding

Avoid unless potential benefit outweighs risk; animal studies have reported excretion into milk with adverse reactions in the offspring.

Storage

Store below 30°C, protect from moisture.

Formulations

• Kerendia 10 mg tablets
• Kerendia 20 mg tablets

Mechanism of action

Finerenone is a non-steroidal selective mineralocorticoid receptor (MR) antagonist with no significant affinity or activity at androgen, progesterone, estrogen, and glucocorticoid receptors. Animal studies have shown that finerenone binding to the MR reduces inflammation and fibrosis, and phase 2 clinical trials showed a reduction in albuminuria. Aldosterone is a mineralocorticoid hormone involved in the regulation of blood pressure, sodium reabsorption, and potassium excretion. In 1943, agonism of the MR along with increased salt was shown to be associated with malignant hypertension, which could progress to inflammation and fibrosis of organs. Binding of aldosterone, an MR agonist, to the MR causes a conformational change, which dissociates the receptor from inactivating chaperone proteins. The active MR translocates to the nucleus along with a complex of other coactivators to induce transcription of a number of genes. Finerenone's binding to the MR prevents binding of MR coactivators, which in turn prevents pro-inflammatory and pro-fibrotic gene transcription. Clinical trial data shows that blocking the mineralocorticoid receptor reduces mortality and morbidity in patients with chronic severe congestive heart failure with an ejection fraction ≤35%. Patients taking finerenone developed new onset atrial fibrillation or flutter (AFF) with a hazard ratio of 0.71. Finerenone lowered the risk of first onset of kidney failure, a sustained eGFR decrease of ≥40%, or death from a renal cause to a hazard ratio of 0.82. Cardiovascular outcomes including cardiovascular death, nonfatal heart attacks, nonfatal strokes, and hospitalization for heart failure in patients taking finerenone had a hazard ratio of 0.86 in patients with a history of AFF and 0.85 in patients without a history of AFF.

Pharmacodynamics

Finerenone is a non-steroidal mineralocorticoid receptor antagonist indicated to reduce the risk of sustained decline in glomerular filtration rate, end stage kidney disease, cardiovascular death, heart attacks, and hospitalization due to heart failure in adults with chronic kidney disease associated with type II diabetes mellitus. It has a moderate duration of action as it is taken once daily, and a wide therapeutic window as patients were given doses from 1.25 mg to 80 mg in clinical trials. Patients should be counselled regarding the risk of hyperkalemia.