mineralocorticoid receptor antagonists non steroidal
Chronic kidney disease (CKD) associated with type 2 diabetes.
Acts as a nonsteroidal, selective antagonist of the mineralocorticoid receptor, which results in reduction in sodium reabsorption and a reduction in fibrosis and inflammation in the heart, blood vessels, and kidneys.
Reduction in the risk of a sustained eGFR decline, end-stage kidney disease, cardiovascular death, nonfatal MI, and hospitalization for HF in CKD associated with type 2 diabetes.
Absorption: 44% absorbed following oral administration.
Distribution: Widely distributed to tissues.
Protein Binding: 92%.
Metabolism and Excretion: Primarily metabolized in the liver via the CYP3A4 isoenzyme, and to a lesser extent by the CYP2C8 isoenzyme to inactive metabolites. Primarily excreted in the urine (80%) as metabolites, with 20% being excreted in feces.
Half-life: 2–3 hr.
TIME/ACTION PROFILE (plasma concentrations)
|PO||rapid||30 min–1.25 hr||unknown|
- Concurrent use of strong CYP3A4 inhibitors;
- Adrenal insufficiency;
- Hyperkalemia (serum potassium >5 mEq/L);
- eGFR <25 mL/min/m2 ;
- Severe hepatic impairment;
- Lactation: Lactation.
Use Cautiously in:
- Renal impairment (↑ risk of hyperkalemia) (adjust dose);
- Moderate hepatic impairment;
- OB: Safety not established in pregnancy;
- Pedi: Safety and effectiveness not established in children.
Adverse Reactions/Side Effects
F and E: hyperkalemia, hyponatremia
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
Strong CYP3A4 inhibitors may significantly ↑ levels and risk of hyperkalemia; concurrent use contraindicated.
- Moderate CYP3A4 inhibitors, including erythromycin or weak CYP3A4 inhibitors, including amiodarone, may ↑ levels and risk of hyperkalemia; closely monitor serum potassium levels after initiation of or after dosage adjustment of either the CYP3A4 inhibitor or finerenone.
- Strong CYP3A4 inducers, including rifampin, or moderate CYP3A4 inducers, including efavirenz, may ↓ levels and effectiveness; avoid concurrent use.
- Use with ACE inhibitors, NSAIDs, potassium supplements, angiotensin II receptor antagonists, potassium-sparing diuretics, angiotensin converting enzyme inhibitors, or cyclosporine ↑ risk of hyperkalemia.
Grapefruit juice or grapefruit may ↑ levels and risk of hyperkalemia; avoid concomitant use.
PO (Adults): 20 mg once daily.
PO (Adults): eGFR 25–<60 mL/min/m2 : 10 mg once daily; after 4 wk, may ↑ to 20 mg once daily if serum potassium ≤4.8 mEq/L.
Tablets: 10 mg, 20 mg
- Monitor for signs and symptoms of hyperkalemia (fatigue, muscle weakness, paresthesia, confusion, dyspnea, cardiac arrhythmias) during therapy. If symptoms occur, confirm with serum potassium.
Lab Test Considerations:
Measure serum potassium levels and eGFR before starting therapy. Do not start therapy if serum potassium is >5.0 mEq/L.
- Measure serum potassium 4 wk after starting therapy and adjust dose. If serum potassium is ≤4.8 mEq/L, ↑ dose to 20 mg, if at 10 mg/day or maintain 20 mg/day dose. If serum potassium levels are >4.8 to 5.5 mEq/L, maintain current 10 mg/day or 20 mg/day dose. If serum potassium is >5.5 mEq/L, hold finerenone dose. If at 10 mg/day dose, consider restarting at 10 mg/day once serum potassium is ≤5.0 mEq/L. If at 20 mg/day dose, restart at 10 mg/day when serum potassium is ≤5.0 mEq/L. Monitor serum potassium 4 weeks after a dose adjustment and throughout treatment, and adjust the dose as needed.
- PO For patients unable to swallow tablets whole, tablets may be crushed and mixed with water or soft foods (applesauce) immediately before use.
- Instruct patient to take finerenone as directed. Take missed dose as soon as remembered, but only on same day. Do not double doses.
- Advise patients to consult with health care professional before using potassium supplements or salt substitutes containing potassium.
- Caution patient to avoid grapefruit and grapefruit juice during therapy; may increase the plasma concentration of finerenone.
- Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
- Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during and for 1 day after last dose.
- Emphasize the importance of regular lab test to monitor potassium levels.
Reduction of the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, nonfatal MI, and hospitalization for HF in patients with CKD associated with type 2 diabetes