OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NO.	MOLECULAR FORMULA	STRUCTURE
Finerenone	1050477-31-0	C21-H22-N4-O3

ANNOTATED BIBLIOGRAPHY

References updated: 13 October 2023

Abbreviations: ACE, angiotensin converting enzyme; ARB, angiotensin receptor blocker; eGFR, estimated glomerular filtration rate; SGLT2, sodium-glucose cotransporter 2.

• Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.

  (Review of hepatotoxicity published in 1999 before the availability of finerenone mentions that thiazide diuretics have been implicated in rare instances of hepatotoxicity but does not discuss spironolactone or finerenone).
• FDA. https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2021/215341Orig1s000IntegratedR.pdf

  (FDA Drug Approvals website that has product labels [package inserts], letters of approval and full FDA integrated review of the finerenone application for safety and efficacy which mentions [page 54] that laboratory findings other than those of electrolytes and creatinine “did not reveal any other findings of interest or concern”).
• Pitt B, Kober L, Ponikowski P, Gheorghiade M, Filippatos G, Krum H, Nowack C, et al. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial. Eur Heart J. 2013; 34: 2453-63. [PMC free article: PMC3743070] [PubMed: 23713082]

  (Among 457 patients with chronic renal disease treated with different doses of finerenone [2.5, 5 or 10 mg daily], spironolactone or placebo for 4 weeks, there was less hyperkalemia with finerenone than spironolactone and adverse events were generally mild; no mention of ALT elevations or hepatotoxicity).
• Bakris GL, Agarwal R, Chan JC, Cooper ME, Gansevoort RT, Haller H, Remuzzi G, et al.; Mineralocorticoid Receptor Antagonist Tolerability Study–Diabetic Nephropathy (ARTS-DN) Study Group. Effect of finerenone on albuminuria in patients with diabetic nephropathy: A randomized clinical trial. JAMA. 2015; 314: 884-94. [PubMed: 26325557]

  (Among 821 patients with diabetes and albuminuria treated with 7 different doses of finerenone [1.25 to 25 mg daily] or spironolactone or placebo for 4 weeks, there was a dose-dependent decrease in urinary albumin while hyperkalemia arose with higher doses of finerenone; no mention of ALT levels or hepatotoxicity).
• Filippatos G, Anker SD, Böhm M, Gheorghiade M, Køber L, Krum H, Maggioni AP, et al. A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease. Eur Heart J. 2016; 37: 2105-14. [PMC free article: PMC4946749] [PubMed: 27130705]

  (Among 821 adults with diabetes and albuminuria treated with one of 7 different doses of finerenone [1.25 to 25 mg] or placebo once daily for 90 days, there was a dose-dependent reduction in urinary albumin levels in finerenone treated patients and an increased rate of hyperkalemia with the higher doses; no mention of ALT levels or hepatotoxicity).
• Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM, Rossing P, Kolkhof P, et al.; FIDELIO-DKD Investigators. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020; 383: 2219-2229. [PubMed: 33264825]

  (Among 5674 patients with chronic kidney disease and type 2 diabetes treated with finerenone [20 mg daily] or placebo for a median of 2.6 years, finerenone was associated with lower rates of a combined endpoint of renal failure, a decrease in eGFR [40%] and lower rates of renal death [18% vs 21%], but no difference in overall mortality or hospitalization, while adverse event rates were similar in the two groups including those classified as “hepatobiliary” [4.4% vs 4.8%], while discontinuations because of hyperkalemia occurred in 2.3% vs 0.9%).
• Ingelfinger JR, Rosen CJ. Finerenone–halting relative hyperaldosteronism in chronic kidney disease. N Engl J Med. 2020; 383: 2285-2286. [PubMed: 33095527]

  (Editorial in response to Bakris [2020] discusses the role of aldosterone activation in causing sodium retention but also release of mediators of inflammation and fibrosis, which has led to strategies to decrease aldosterone activation as therapy of chronic renal disease).
• Allison SJ. Finerenone in chronic kidney disease. Nat Rev Nephrol. 2021; 17: 13. [PubMed: 33110253]

  (Commentary on the results of treating patients with chronic kidney disease with long term finerenone [Bakris 2020] and role of aldosterone activation in causing inflammation and fibrosis leading to progression of renal and heart disease, mentions that an ongoing trial will assess the effects of finerenone on patients with less advanced chronic renal disease).
• Heinig R, Gerisch M, Engelen A, Nagelschmitz J, Loewen S. Pharmacokinetics of the novel, selective, non-steroidal mineralocorticoid receptor antagonist finerenone in healthy volunteers: results from an absolute bioavailability study and drug-drug interaction studies in vitro and in vivo. Eur J Drug Metab Pharmacokinet. 2018;43:715-727. [PubMed: 29779093]

  (Evaluation of pharmacokinetics of finerenone in health volunteers found that it was metabolized mostly by CYP 3A4 and to a lesser extent by CYP 2C8, but only CYP 3A4 inducers and inhibitors had an effect on finerenone levels).
• Agarwal R, Filippatos G, Pitt B, Anker SD, Rossing P, Joseph A, Kolkhof P, et al.; FIDELIO-DKD and FIGARO-DKD investigators. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. Eur Heart J. 2022;43:474-484. [PMC free article: PMC8830527] [PubMed: 35023547]

  (Pooled analysis of two randomized controlled trials of finerenone [10 or 20 mg] versus placebo in patients with type 2 diabetes and chronic renal disease in 13,026 adults with median follow up of 3 years found lower rates of composite endpoints of cardiovascular events and worsening renal function with finerenone therapy [12.7% vs 14.4%], with similar adverse event rates [86.1% vs 86.4%] but higher rates of hyperkalemia [12% vs 6%]; no mention of ALT elevations or hepatotoxicity).
• Finerenone (Kerendia) for chronic kidney disease. Med Lett Drugs Ther. 2021;63:131-132. [PubMed: 34544101]

  (Concise summary of the mechanism of action, clinical efficacy, safety, and costs of finerenone shortly after its approval in the US, mentions adverse events of hyperkalemia, hyponatremia, and hypotension; no mention of ALT elevations or hepatotoxicity).
• Rossing P, Anker SD, Filippatos G, Pitt B, Ruilope LM, Birkenfeld AL, McGill JB, et al.; FIDELIO-DKD and FIGARO-DKD Investigators. Finerenone in patients with chronic kidney disease and type 2 diabetes by sodium-glucose cotransporter 2 inhibitor treatment: The FIDELITY Analysis. Diabetes Care. 2022;45:2991-2998. [PMC free article: PMC9862372] [PubMed: 35972218]

  (Re-analysis of trials of finerenone in patients with chronic renal disease and diabetes showed that it was effective in the subgroup of patients receiving SGLT2 inhibitors with no difference in tolerance).
• In brief: Finerenone (Kerendia) for diabetic kidney disease. Med Lett Drugs Ther. 2023;65:15-16. [PubMed: 36651794]

  (Brief summary of the mechanism of action, clinical efficacy and safety of finerenone shortly after published guidelines on its use were published, mentions that finerenone has been shown to modestly improve renal and cardiovascular outcomes, but it is expensive and can cause hyperkalemia).
• Perakakis N, Bornstein SR, Birkenfeld AL, Linkermann A, Demir M, Anker SD, Filippatos G, et al.; FIDELIO-DKD and FIGARO-DKD investigators. Efficacy of finerenone in patients with type 2 diabetes, chronic kidney disease and altered markers of liver steatosis and fibrosis: A FIDELITY subgroup analysis. Diabetes Obes Metab. 2023 Oct 10. Epub ahead of print. [PubMed: 37814928]

  (Re-analysis of trials of finerenone in patients with chronic renal disease and diabetes focusing upon the subgroup of patients with evidence of concurrent nonalcoholic fatty liver disease found similar efficacy and safety as in patients without evidence of liver abnormalities and that liver tests did not worsen with treatment).