Introduction
Kerendia (finerenone) is a nonsteroidal mineralocorticoid receptor antagonist (MRA) developed by Bayer Pharmaceuticals. It represents a novel therapeutic class for addressing chronic kidney disease (CKD) associated with type 2 diabetes. Approved by the FDA in July 2021, Kerendia offers a targeted approach to reducing kidney and cardiovascular complications in this high-risk patient population.
Mechanism of Action
Finerenone selectively inhibits the mineralocorticoid receptor (MR) in the kidney, heart, and blood vessels. Unlike traditional steroidal MRAs, finerenone demonstrates more balanced tissue distribution between the kidneys and heart. MR overactivation contributes to inflammation and fibrosis in these tissues, which are key drivers of CKD progression and cardiovascular damage in diabetic patients. By blocking these pathological effects, finerenone reduces albuminuria and slows CKD progression while providing cardiovascular protection.
Indications
Kerendia is indicated to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, nonfatal myocardial infarction, and hospitalization for heart failure in adult patients with chronic kidney disease associated with type 2 diabetes.
Dosage and Administration
Standard dosing:- Initial dose: 10 mg or 20 mg orally once daily based on eGFR
- Target dose: 20 mg once daily
- eGFR ≥ 60 mL/min/1.73m²: Start with 20 mg once daily
- eGFR 25 to <60 mL/min/1.73m²: Start with 10 mg once daily
- eGFR <25 mL/min/1.73m²: Not recommended
- After 4 weeks, increase from 10 mg to 20 mg once daily if serum potassium is ≤4.8 mEq/L
- Hepatic impairment: No dose adjustment needed
- Renal impairment: See dosing recommendations above
- Geriatric patients: No dose adjustment required
- Pediatric patients: Safety and effectiveness not established
Pharmacokinetics
Absorption: Rapidly absorbed with median Tmax of 0.5-1.25 hours. Absolute bioavailability approximately 44%. Food does not clinically affect absorption. Distribution: Volume of distribution ~52 L. Protein binding approximately 92%, primarily to albumin. Metabolism: Primarily via CYP3A4 with minor contributions from CYP2C8. Forms inactive metabolites. Elimination: Elimination half-life ~2-3 hours. Excretion primarily fecal (80.5%) with minor renal elimination (19.5%).Contraindications
1. Concomitant use with strong CYP3A4 inhibitors 2. Patients with adrenal insufficiency 3. Serum potassium >5.0 mEq/L at initiation 4. Hypersensitivity to finerenone or any component of the formulation
Warnings and Precautions
Hyperkalemia: Kerendia can cause hyperkalemia. Risk is higher in patients with baseline renal impairment, those taking other medications that increase potassium, and elderly patients. Monitor serum potassium regularly and adjust dose or discontinue as needed. Hypotension: May occur, particularly in volume-depleted patients or those taking other antihypertensive agents. Acute Kidney Injury: Monitor renal function periodically, especially in patients with pre-existing renal impairment. Drug-induced adrenal insufficiency: Although rare with nonsteroidal MRAs, monitor for signs and symptoms.Drug Interactions
Strong CYP3A4 inhibitors: Contraindicated (e.g., ketoconazole, itraconazole, clarithromycin) Moderate CYP3A4 inhibitors: Use with caution and monitor potassium (e.g., erythromycin, fluconazole, diltiazem) CYP3A4 inducers: May decrease finerenone exposure (e.g., rifampin, carbamazepine) Potassium-increasing drugs: Increased hyperkalemia risk with ACE inhibitors, ARBs, NSAIDs, potassium-sparing diuretics, potassium supplements Other nephrotoxic drugs: Increased risk of renal impairmentAdverse Effects
Common (≥2%):- Hyperkalemia (18.3%)
- Hypotension (4.8%)
- Hyponatremia (1.4%)
- Severe hyperkalemia (≥6.0 mEq/L: 2.6%)
- Hospitalization for hyperkalemia (0.9%)
- Acute kidney injury
Monitoring Parameters
1. Serum potassium: Baseline, at 4 weeks after initiation or dose increase, and periodically thereafter 2. Renal function: eGFR and serum creatinine at baseline and regularly during treatment 3. Blood pressure: Regular monitoring, especially during initiation 4. Serum sodium: Periodically 5. Signs/symptoms of hyperkalemia: Muscle weakness, irregular heartbeat, nausea 6. Adrenal insufficiency symptoms: Fatigue, dizziness, nausea, vomiting
Patient Education
- Take Kerendia exactly as prescribed, once daily with or without food
- Do not stop taking without consulting your healthcare provider
- Report any symptoms of high potassium levels: muscle weakness, irregular heartbeat, nausea
- Inform all healthcare providers about all medications you're taking, including over-the-counter drugs and supplements
- Regular blood tests are necessary to monitor potassium levels and kidney function
- Maintain consistent dietary potassium intake; avoid excessive potassium-rich foods
- Report dizziness or lightheadedness, especially when standing up
- Use effective contraception if of reproductive potential
- Store at room temperature away from moisture and heat
References
1. FDA prescribing information: Kerendia (finerenone) tablets. July 2021. 2. Bakris GL, Agarwal R, Anker SD, et al. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med. 2020;383(23):2219-2229. 3. Pitt B, Filippatos G, Agarwal R, et al. Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes. N Engl J Med. 2021;385(24):2252-2263. 4. Agarwal R, Filippatos G, Pitt B, et al. 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(6):474-484. 5. Kintscher U, Bakris GL, Agarwal R, et al. Finerenone in Predominantly Advanced CKD and Type 2 Diabetes With or Without Heart Failure: A FIDELITY Subgroup Analysis. Am J Kidney Dis. 2022;79(2):236-245.