KERENDIA
Clinical safety rating: caution
Comprehensive 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KERENDIA (KERENDIA).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. Excreted in rat milk. M/P ratio unknown. Due to potential for serious adverse reactions (e.g., hyperkalemia, hypotension), breastfeeding is not recommended during therapy and for 1 week after last dose. |
| 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. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
["Concomitant use with strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, ketoconazole, ritonavir).","Addison's disease (adrenal insufficiency).","Serum potassium > 5.0 mEq/L at initiation."]
| 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)."] |
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| 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. |