フィネレノン

Breast Feeding; Lactation; Mineralocorticoid Receptor Antagonists

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

FDA approved drugs -> Active ingredient

Danger

H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]

P203, P260, P263, P264, P270, P273, P280, P301+P316, P318, P319, P321, P330, P391, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 3 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

In placebo-controlled trials of finerenone in several thousand patients, there was usually no mention of serum enzyme elevations or hepatotoxicity. In the largest placebo controlled trial, the rate of “hepatobiliary” adverse events was similar in patients on finerenone compared to placebo (4.4% vs 4.8%), and there were no reported hepatic serious adverse events. Since its approval and more widespread use, finerenone has not been implicated in instances of acute hepatic injury and the product label does not mention aminotransferase elevations or clinically apparent liver injury in lists of potential adverse events.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Finerenone

vNo-DILI-concern

0

No match

DOI:10.1016/j.drudis.2016.02.015

C - Cardiovascular system

QC - Cardiovascular system

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.

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.