KERENDIA
Clinical safety rating
cautionComprehensive clinical and safety monograph for KERENDIA (KERENDIA).
Finerenone is a nonsteroidal, selective antagonist of the mineralocorticoid receptor (MR). It binds to the MR and inhibits the recruitment of coactivators, thereby reducing the expression of pro-inflammatory and pro-fibrotic mediators in the kidney and heart.
| Metabolism | Primarily metabolized by CYP3A4 (≈90%) and to a lesser extent by CYP2C8 (≈10%). No active metabolites. |
| Excretion | Approximately 80% of the dose is eliminated via feces (primarily as unchanged drug) and ~20% via urine (mostly as metabolites). Renal excretion of unchanged drug is minimal (less than 1%). |
| Half-life | The terminal elimination half-life is approximately 2–4 hours in healthy subjects. In patients with renal impairment, the half-life may be prolonged up to 6–8 hours, allowing for once-daily dosing in chronic kidney disease. |
| Protein binding | Approximately 92% bound to plasma proteins, primarily albumin and alpha-1 acid glycoprotein. |
| Volume of Distribution | The apparent volume of distribution is approximately 50 L (about 0.7 L/kg in a 70 kg adult), indicating moderate tissue distribution, likely into kidney and heart tissues. |
| Bioavailability | Oral bioavailability is about 90–95% in healthy subjects, indicating nearly complete absorption after oral administration. Food does not significantly affect absorption. |
| Onset of Action | Oral administration: Clinical effects on potassium excretion and blood pressure begin within 1–2 hours after a single dose, with maximum effect on urinary sodium/potassium ratio observed around 4–6 hours post-dose. |
| Duration of Action | Duration of pharmacodynamic effect (e.g., increased urinary sodium/potassium ratio) persists for approximately 12–24 hours, supporting once-daily dosing. Note: Continuous daily dosing is required for sustained clinical benefit in heart failure and CKD. |
| Molecular Weight | 378.41 |
10 mg orally once daily initially, then titrate to 20 mg once daily after 4 weeks if tolerated.
| Dosage form | TABLET |
| Renal impairment | eGFR 25-59 mL/min/1.73 m²: Initiate 10 mg once daily; continue 10 mg if tolerated. eGFR <25 mL/min: Not recommended. |
| Liver impairment | Child-Pugh B (moderate impairment): 10 mg once daily. Child-Pugh C (severe impairment): Not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment required; monitor renal function closely. |
| 1st trimester | There are no adequate data on the use of Kerendia (finerenone) in pregnant women; animal studies have shown reproductive toxicity. Due to the potential for harm to the fetus, use during the first trimester is not recommended unless clearly necessary. |
| 2nd trimester | Use during the second trimester is not recommended due to the potential for fetal harm based on animal studies and its mechanism of action as a mineralocorticoid receptor antagonist. |
| 3rd trimester | Use during the third trimester may cause potential harm to the fetus (e.g., oligohydramnios, renal dysfunction, skull ossification defects) and is not recommended. |
Clinical note
Comprehensive clinical and safety monograph for KERENDIA (KERENDIA).
| Placental transfer | Animal studies have shown that finerene crosses the placenta. There is no human data on placental transfer, but given its molecular weight and lipophilicity, placental transfer is expected. |
| Breastfeeding | It is unknown whether finerene or its metabolites are excreted in human milk. A risk to the breastfed infant cannot be excluded. Decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. |
| Lactation Rating | L4 |
| Teratogenic Risk | Based on animal studies, Kerendia (finerenone) is associated with fetal harm. In rats, embryofetal toxicity (reduced fetal weights, delayed ossification) and malformations (cardiovascular, skeletal) were observed at maternal exposures below the maximum recommended human dose. In rabbits, increased post-implantation loss and decreased fetal weights occurred. There are no adequate human studies. Use is contraindicated in pregnancy. Avoid in women of childbearing potential not using effective contraception. |
| Fetal Monitoring | Monitor serum potassium and renal function at baseline and periodically during treatment. In pregnant women inadvertently exposed, monitor fetal growth via ultrasound and assess amniotic fluid volume. Closely monitor for maternal hyperkalemia, hypotension, and renal impairment. |
| Fertility Effects | In animal studies, finerenone had no adverse effects on male or female fertility at exposures up to 4-5 times the human AUC at the maximum recommended dose. No human data on fertility effects. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
Concomitant use with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, ritonavir, clarithromycin)Addison's diseaseSerum potassium > 5.0 mEq/L at initiationPatients with severe hepatic impairment (Child-Pugh C)
| Precautions | Hyperkalemia: Monitor serum potassium levels; may require dose adjustment or discontinuation., Hypotension: Risk increased in patients with volume depletion or concomitant antihypertensive therapy., Acute kidney injury: Monitor renal function; consider temporary discontinuation in setting of significant renal impairment., Hepatic impairment: Not recommended in patients with severe hepatic impairment (Child-Pugh C). |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they inhibit CYP3A4 and may increase finerenone exposure. No other food interactions noted. |
| Clinical Pearls | Monitor serum potassium closely, especially in patients with eGFR <30 mL/min/1.73m² or baseline K+ >5.0 mEq/L. Avoid use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir). Contraindicated with concomitant mineralocorticoid receptor antagonists (e.g., spironolactone, eplerenone). Use caution with moderate CYP3A4 inhibitors (e.g., erythromycin, verapamil) and moderate CYP3A4 inducers (e.g., rifampin, phenytoin). Assess eGFR and serum potassium before initiation and at 1 month after starting or adjusting dose. |
| Patient Advice | Take this medication exactly as prescribed, usually once daily with or without food. · Do not use potassium supplements or salt substitutes containing potassium without consulting your doctor. · Report symptoms of hyperkalemia (e.g., muscle weakness, fatigue, palpitations, numbness) immediately. · Avoid grapefruit and grapefruit juice during treatment. · Inform all healthcare providers that you are taking KERENDIA (finerenone). · Do not stop taking KERENDIA without talking to your doctor. · Store at room temperature, away from moisture and heat. |
Loading safety data…