Confirmation of Clinical indications
· Statistically significant improvement in cardiovascular and renal outcomes, in persons with type 2 diabetes and DKD, as reported by the FIDELIO, FIGARO and FIDELITY results.
· Finerenone is indicated to reduce the risk of sustained estimated glomerular filtration rate (eGFR) decline, end-stage kidney disease, cardiovascular death, nonfatal myocardial infarction and hospitalization for heart failure in adult patients with CKD associated with type 2 diabetes.
· Initiation of finerenone treatment is recommended in CKD and type 2 diabetes persons with an eGFR >25 mL/min/1.73 m2, or with UACR >30 mg/g, and with normokalemia.
Caveats and Contraindications
Caveats
· No approved so far on persons with type 1 diabetes.
· No approved so far on persons with non-DKD.
· Not indicated for use in heart failure or refractory hypertension.
Contraindications
End-stage renal disease.
· Initiation is not recommended if serum potassium >5.0 mmol/L (5 mEq/L).
· Severe hepatic impairment (Child-Pugh C).
· Addison’s disease.
· Preconception, pregnancy and lactation.
Concerns and Checkpoints
Concerns
· The risk of side effects is less with finerenone than with earlier mineralocorticoid receptor antagonists such as spironolactone and eplerenone.
· Hyperkalemia leading to permanent discontinuation may occur in ≈2% of patients and the risk of sexual and other side effects is minimal.
Checkpoints
· Serum potassium must be monitored 1 month after onset of therapy, at regular (≈4 monthly) intervals thereafter, and whenever a change in electrolyte levels is anticipated or suspected, e.g., vomiting, diarrhea, addition of diuretics, renotoxic drugs, other concomitant medication, which may interfere with finerenone metabolism.
· While there is no specific recommendation for the frequency and regularity of monitoring UACR, it would be prudent to assess this 4 months after onset of therapy. More frequent assessment may be justified if it can help allay patient anxiety and/or inform changes in choice and/or dosage of finerenone/concomitant therapy.
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Caution and Concomitant usage
Caution during use
· Finerenone is a once-daily oral tablet that can be taken at any time of the day.
· Begin with 10 mg/day finerenone in persons with eGFR <60mL/min/1.73 m2, and 20 mg/day in those with eGFR >60 mL/min/1.73 m2.
· If potassium levels are normal (<4.8 mEq/L) after 1 month, up-titrate to 20 mg/day.
· If potassium levels are >5.5 mEq/L, withhold finerenone; check potassium after a few days (as it has a short half-life), and restart 10 mg/day if serum potassium ≤5.0 mEq/L.
· If potassium levels are between 4.8 and 5.0 mEq/L, maintain the dose and take an individualized, case-based decision, keeping in mind the risk benefit ratio of continuing finerenone and assessing the ability to screen for hyperkalemia, and manage it if needed.
Concomitant medication
· No extra diuresis occurs with finerenone, and it can be used with thiazide, thiazide-like, and loop diuretics.
· Finerenone is not indicated with other mineralocorticoid receptor antagonists, spironolactone and eplerenone.
· In a patient who has been on spironolactone or eplerenone for an indication such as hypertension or heart failure, and now needs finerenone for management of DKD, an individualized needs and priority assessment should be done.
· Finerenone is not contraindicated in patients taking concomitant medications that are strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, ritonavir, nelfinavir, cobicistat, clarithromycin, telithromycin and nefazodone).
· Concomitant intake of strong CYP3A enzyme inducers like rifampicin, carbamazepine, phenytoin, phenobarbital and St John’s Wort may lead to decrease in plasma concentration of finerenone and results in reduced therapeutic effect and should be avoided.
· Finerenone can be used with all glucose-lowering drugs, including SGLT2 inhibitors.
Constraints and Cost
· Share details about the cost of therapy with the patient, especially in a pay-from-pocket scenario, and assist in performing an informal cost-benefit analysis.
· Explain that the cost of 10 mg and 20 mg tablets is same, to preclude suboptimal dosing.
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