Side Effects of Finerenone
The primary side effect of finerenone is hyperkalemia, occurring in approximately 10.8% of patients compared to 5.3% with placebo, though discontinuation rates remain low at 2.3%. 1, 2, 3
Primary Safety Concern: Hyperkalemia
- Hyperkalemia is the most clinically significant adverse effect, with a relative risk of 2.07 (95% CI 1.77-2.44) compared to placebo across heart failure populations 3
- The risk increases as renal function declines, making early initiation when eGFR is preserved a strategy to minimize this complication 4
- Hyperkalemia-related discontinuation occurs in 1.2% of finerenone patients versus 0.4% with placebo 5
- Serum potassium must be ≤4.8 mmol/L before initiating finerenone and requires regular monitoring throughout treatment 6, 2
Cardiovascular Side Effects
- Hypotension occurs with increased frequency, with a relative risk of 1.49 (95% CI 1.31-1.68) compared to placebo 3
- This effect is consistent across all heart failure phenotypes (HFrEF, HFmrEF, HFpEF) 3
Renal Function Changes
- Finerenone causes an initial hemodynamic decrease in eGFR of approximately -2.9 mL/min/1.73 m² during the first 3 months of treatment 7
- This initial decline may reflect increases in blood urea nitrogen (BUN) but does not represent true renal damage 7
- The chronic slope of eGFR from 3 months onwards remains unchanged compared to placebo, indicating no long-term deterioration 7
General Tolerability Profile
- Overall treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) do not differ significantly from placebo when analyzing the general heart failure population 3
- Treatment discontinuation rates due to adverse events are similar between finerenone and placebo 3
- Finerenone demonstrates superior tolerability compared to steroidal MRAs, with lower rates of TEAEs (RR 0.93) and TESAEs (RR 0.74) versus eplerenone 3
Advantages Over Steroidal MRAs
- Finerenone does not cause gynecomastia or sexual dysfunction, unlike spironolactone, because it lacks a steroid skeleton 1, 8
- Compared to spironolactone in HFrEF patients, finerenone shows lower risks of TEAEs (RR 0.64), treatment discontinuation (RR 0.37), and hyperkalemia (RR 0.41) 3
- The nonsteroidal structure provides equal affinity for epithelial and non-epithelial tissues, resulting in relatively weaker effects on renal tubules and lower potassium-sparing diuretic effects 4
Critical Monitoring Requirements
- Verify serum potassium ≤4.8 mmol/L before starting and monitor at 4 weeks after initiation, then regularly throughout treatment 6, 2, 7
- Withhold finerenone if potassium rises >5.5 mmol/L and restart at 10 mg daily when potassium returns to ≤5.0 mmol/L 6, 2
- Monitor baseline renal function (eGFR, creatinine, BUN) and reassess at 4 weeks, especially in patients with eGFR <60 mL/min/1.73 m² 7
Contraindications and Precautions
- Do not initiate if eGFR <25 mL/min/1.73 m² as landmark trials excluded this population and no safety data exists for end-stage renal disease 6, 7
- Finerenone is contraindicated in patients with adrenal insufficiency 1
- Consider using oral potassium adsorbents proactively to prevent hyperkalemia and allow continuation of therapy rather than waiting to treat elevated potassium 4