What is the equivalent dose of amiloride for a patient taking 12.5 mg of Aldactone (spironolactone) daily?

Equivalent Dose of Amiloride for Spironolactone 12.5 mg

For a patient taking 12.5 mg of spironolactone (Aldactone) daily, the equivalent dose of amiloride for equal biological effectiveness is 5 mg daily.

Mechanism of Action and Equivalence

Both spironolactone and amiloride are potassium-sparing diuretics, but they work through different mechanisms:

• Spironolactone: Acts as an aldosterone receptor antagonist (mineralocorticoid receptor antagonist)
• Amiloride: Directly blocks sodium channels in the distal tubule

Despite their different mechanisms, both medications achieve similar clinical effects in terms of natriuresis, potassium retention, and blood pressure reduction.

Evidence Supporting the Equivalence

The most recent high-quality evidence comes from a 2025 randomized clinical trial published in JAMA that directly compared spironolactone and amiloride in patients with resistant hypertension 1. This study demonstrated that:

• 5 mg of amiloride was equivalent to 12.5 mg of spironolactone as an initial dose
• 10 mg of amiloride was equivalent to 25 mg of spironolactone when dose escalation was needed
• Amiloride was noninferior to spironolactone in lowering systolic blood pressure

This equivalence ratio of approximately 1:2.5 (amiloride:spironolactone) is consistent with earlier research from 2018 that showed amiloride 10 mg produced similar blood pressure reductions as spironolactone 25 mg in resistant hypertension 2.

Clinical Considerations When Switching Between Medications

When transitioning a patient from spironolactone to amiloride, consider:

1. Monitoring requirements:

   • Check baseline potassium and renal function before switching
   • Monitor potassium and renal function within 2-3 days after switching
   • Continue monitoring at 7 days, then monthly for the first 3 months 3

2. Contraindications:

   • Avoid in patients with:
     • Serum creatinine >2.5 mg/dL in men or >2.0 mg/dL in women
     • eGFR <30 mL/min/1.73m²
     • Baseline potassium >5.0 mEq/L 4, 3

3. Advantages of amiloride over spironolactone:

   • Fewer endocrine side effects (no gynecomastia, erectile dysfunction, or menstrual irregularities)
   • Once-daily dosing due to longer duration of action than triamterene 5
   • Similar antihypertensive efficacy 2, 1

Practical Dosing Algorithm

For a patient currently on spironolactone 12.5 mg daily:

1. Initial conversion: Start amiloride at 5 mg once daily
2. Monitoring: Check potassium and renal function within 2-3 days
3. Dose adjustment:
   • If blood pressure control is inadequate and potassium <5.0 mmol/L, increase to 10 mg daily
   • If potassium rises to 5.5-5.9 mmol/L, reduce dose by 50%
   • If potassium ≥6.0 mmol/L, discontinue medication 3

Important Precautions

• Discontinue potassium supplements when initiating either medication
• Counsel patients to avoid high-potassium foods
• Instruct patients to temporarily stop the medication during episodes of diarrhea, vomiting, or dehydration
• Avoid NSAIDs and COX-2 inhibitors which can worsen renal function and increase hyperkalemia risk 3

Both medications are effective alternatives to each other, with the choice between them often guided by the side effect profile and patient-specific factors.