At what potassium level should Kerendia (finerenone) be held due to risk of hyperkalemia?

Hold Kerendia at Potassium ≥5.5 mmol/L

Kerendia (finerenone) should be temporarily withheld when serum potassium rises to >5.5 mmol/L, with reinitiation at a reduced dose (10 mg daily) only after potassium decreases to ≤5.0 mmol/L. 1

Potassium Thresholds for Finerenone Management

Withholding Criteria

• Temporarily discontinue finerenone when potassium exceeds 5.5 mmol/L 1
• Do not restart until potassium falls to ≤5.0 mmol/L 1
• When restarting, reduce dose to 10 mg daily regardless of prior dose 1

Permanent Discontinuation Threshold

• Stop finerenone immediately if potassium reaches ≥6.0 mmol/L 2
• This threshold represents moderate hyperkalemia requiring urgent intervention 1

Clinical Context from FIDELIO-DKD Trial

The pivotal trial data demonstrates that finerenone carries substantial hyperkalemia risk but can be managed safely with appropriate monitoring:

• 21.4% of finerenone-treated patients experienced potassium >5.5 mmol/L over 2.6 years 1
• 4.5% experienced moderate hyperkalemia (>6.0 mmol/L) 1
• Risk was 2.16 times higher than placebo for potassium >5.5 mmol/L 3

The protocol-directed surveillance and dose adjustment strategy successfully minimized hyperkalemia impact while preserving clinical benefit 1

Risk Factors Requiring Enhanced Vigilance

Independent predictors of hyperkalemia with finerenone include:

• Higher baseline serum potassium (even within normal range) 1
• Lower eGFR at baseline 1
• Higher urine albumin-creatinine ratio 1
• Female sex 1
• Younger age 1
• Concurrent β-blocker use 1

Protective Factors

• Diuretic use reduces hyperkalemia risk 1
• SGLT2 inhibitor use reduces hyperkalemia risk 1

Monitoring Protocol

Frequency

• Check potassium at 1 week, 1 month, 2 months, 3 months, 6 months, then every 6 months after initiation or dose change 2
• More frequent monitoring (every 5-7 days) until values stabilize in high-risk patients 4

Early Warning Signs

• Short-term increases in potassium at month 1-4 predict subsequent hyperkalemia risk 1
• Any potassium rise >0.5 mmol/L from baseline warrants closer surveillance 1
• Concurrent eGFR decline increases hyperkalemia risk 1

Comparison to Other Mineralocorticoid Receptor Antagonists

The management thresholds for finerenone align with established MRA guidelines:

• Spironolactone/eplerenone: halve dose at potassium 5.5-5.9 mmol/L, stop at ≥6.0 mmol/L 2
• Finerenone uses a similar threshold (>5.5 mmol/L) but with mandatory dose reduction to 10 mg on restart 1

Critical Pitfalls to Avoid

Do Not Continue Finerenone Through Mild Hyperkalemia

• Unlike some RAASi where continuation may be considered, finerenone requires temporary discontinuation at >5.5 mmol/L 1
• The 5.5 mmol/L threshold is absolute, not a "consider holding" recommendation 1

Do Not Restart at Previous Dose

• Always restart at 10 mg daily after hyperkalemia resolves, even if patient was previously on 20 mg 1
• Failure to downtitrate increases recurrent hyperkalemia risk 1

Do Not Ignore Concurrent Medications

• Review and potentially discontinue potassium supplements, potassium-sparing diuretics, or NSAIDs before restarting finerenone 2, 5
• Consider adding loop diuretics or SGLT2 inhibitors which reduce hyperkalemia risk 1

Balancing Hyperkalemia Risk with Clinical Benefit

Even patients who develop potassium >5.5 mmol/L on finerenone maintain clinical benefit compared to placebo when hyperkalemia is appropriately managed 3. Both high (>5.5 mmol/L) and low (<3.5 mmol/L) potassium levels increase cardiovascular risk, but finerenone's benefit persists across potassium ranges when protocol-directed management is followed 3.

The target potassium range for optimal outcomes in heart failure patients is 4.0-5.0 mmol/L 2, 6. High-normal potassium (5.0-5.5 mmol/L) is associated with improved survival in heart failure, but exceeding 5.5 mmol/L negates this benefit 6.