What are the considerations for monitoring potassium levels when prescribing lisinopril (Angiotensin-Converting Enzyme (ACE) inhibitor) and spironolactone (aldosterone antagonist) together?

From the Guidelines

Monitoring potassium levels is crucial when prescribing lisinopril and spironolactone together, as the combination increases the risk of hyperkalemia, and patients should be monitored closely, especially those with chronic kidney disease (CKD) or other risk factors for hyperkalemia 1.

Key Considerations

• Baseline potassium levels should be checked before starting therapy, followed by monitoring within 1 week of initiation, again at 4 weeks, and then every 3-6 months during stable therapy, as recommended for patients on mineralocorticoid receptor antagonists like spironolactone 1.
• More frequent monitoring (every 1-2 weeks) is necessary when adjusting doses or during conditions that may affect potassium levels, such as dehydration, diarrhea, or when adding other medications that affect potassium.
• Patients should maintain normal renal function (eGFR >30 mL/min) when using this combination, as CKD is a significant risk factor for hyperkalemia when using ACE inhibitors and spironolactone together 1.

Mechanism and Risks

• The risk of hyperkalemia occurs because both medications reduce potassium excretion through different mechanisms: ACE inhibitors like lisinopril decrease aldosterone production and increase potassium retention, while spironolactone directly blocks aldosterone receptors, further reducing potassium excretion.
• Patients should be educated about symptoms of hyperkalemia (muscle weakness, palpitations, paresthesia) and advised to avoid high-potassium foods and potassium supplements.

Management of Hyperkalemia

• If potassium levels exceed 5.5 mEq/L, dose reduction or discontinuation of one or both medications may be necessary, and other treatments for hyperkalemia should be considered, such as potassium-binding resins or dialysis in severe cases.
• The combination of lisinopril and spironolactone should be avoided in patients with serum creatinine >2.5 mg/dL, or serum K+ >5.0 mmol/L, as recommended for mineralocorticoid receptor antagonists like spironolactone 1.

From the FDA Drug Label

Potassium-sparing diuretics (spironolactone, amiloride, triamterene, and others) can increase the risk of hyperkalemia. Therefore, if concomitant use of such agents is indicated, monitor the patient’s serum potassium frequently. Spironolactone can cause hyperkalemia. This risk is increased by impaired renal function or concomitant potassium supplementation, potassium-containing salt substitutes or drugs that increase potassium, such as angiotensin converting enzyme inhibitors and angiotensin receptor blockers [see Drug Interactions (7. 1)] . Monitor serum potassium within 1 week of initiation or titration of spironolactone and regularly thereafter.

When prescribing lisinopril (Angiotensin-Converting Enzyme (ACE) inhibitor) and spironolactone (aldosterone antagonist) together, the main consideration for monitoring potassium levels is the increased risk of hyperkalemia.

• Key points to consider:
  • Monitor serum potassium frequently when using these drugs concomitantly.
  • Monitor serum potassium within 1 week of initiation or titration of spironolactone and regularly thereafter.
  • More frequent monitoring may be needed when spironolactone is given with other drugs that cause hyperkalemia or in patients with impaired renal function.
  • If hyperkalemia occurs, decrease the dose or discontinue spironolactone and treat hyperkalemia 2 3.

From the Research

Considerations for Monitoring Potassium Levels

When prescribing lisinopril (Angiotensin-Converting Enzyme (ACE) inhibitor) and spironolactone (aldosterone antagonist) together, several considerations should be taken into account for monitoring potassium levels:

• The combination of ACE inhibitors and spironolactone can produce hyperkalemia, especially in patients with renal insufficiency, diabetes, older age, worsening heart failure, a risk for dehydration, and in combination with other medications that may cause hyperkalemia 4.
• Dual renin-angiotensin-aldosterone blockade may impair extrarenal/transcellular potassium disposition in addition to reducing potassium excretion in humans with renal impairment 5.
• Spironolactone raises serum potassium more than losartan in patients with diabetic nephropathy receiving lisinopril, despite similar renal sodium and potassium excretion, suggesting that extrarenal potassium homeostasis contributes to hyperkalemia in these patients 6.
• Factors associated with hyperkalemia from spironolactone therapy include older age, female sex, elevated serum potassium levels, and concurrent potassium supplements 7.
• The addition of spironolactone to loop diuretics in patients with heart failure is associated with a higher risk of hyperkalemia and acute kidney injury, which must be weighed against the potential benefits of spironolactone 8.

Patient-Specific Factors

Patient-specific factors that may increase the risk of hyperkalemia when using lisinopril and spironolactone together include:

• Renal insufficiency
• Diabetes
• Older age
• Worsening heart failure
• Risk for dehydration
• Concurrent use of other medications that may cause hyperkalemia
• Elevated serum potassium levels
• Concurrent potassium supplements

Monitoring and Prevention

To minimize the risk of hyperkalemia, close monitoring of potassium levels is essential, especially in patients with risk factors. This may involve:

• Regular measurement of serum potassium levels
• Monitoring of renal function
• Adjustment of spironolactone dosage
• Avoidance of concurrent use of other medications that may cause hyperkalemia
• Education of patients on the risks of hyperkalemia and the importance of adherence to medication regimens and follow-up appointments.