Amiloride Use and Dosage in Hypertension and Edema
Amiloride should primarily be used as adjunctive therapy with thiazide or loop diuretics in patients with hypertension or edema, particularly when potassium conservation is needed, at an initial dose of 5 mg daily with food, which may be increased to 10 mg daily if necessary. 1
Primary Indications
Amiloride is indicated in the following clinical scenarios:
- To restore normal serum potassium levels in patients who develop hypokalemia on thiazide or loop diuretics
- To prevent hypokalemia in high-risk patients (e.g., those on digoxin or with cardiac arrhythmias)
- As part of combination therapy for resistant edema in nephrotic syndrome
- As a strategy for diuretic-resistant patients with edema
Dosing Protocol
- Initial dose: 5 mg once daily with food 1
- Maximum dose: Can be increased to 10 mg daily if necessary
- Exceptional cases: Doses up to 15-20 mg may be used with careful electrolyte monitoring if persistent hypokalemia is documented 1
- Pediatric dosing: 0.4-0.625 mg/kg/day up to 20 mg/day 2
Combination Therapy
Amiloride is most effective when used in combination with:
- Thiazide diuretics (e.g., hydrochlorothiazide)
- Loop diuretics (e.g., furosemide)
The combination of amiloride with hydrochlorothiazide has been shown to:
- Prevent glucose intolerance associated with thiazide therapy
- Improve blood pressure control compared to monotherapy with either drug
- Counteract hypokalemia from thiazide diuretics 3
Specific Clinical Applications
Resistant Hypertension
Amiloride has been shown to be as effective as spironolactone in resistant hypertension 4, though there is limited data on its use in mild to moderate hypertension across extended dose ranges.
Edema Management
For edema management in heart failure or nephrotic syndrome:
- Use amiloride as adjunctive therapy after initial diuresis with loop diuretics
- Amiloride may reduce potassium loss and improve diuresis in resistant cases 2
- Reevaluate the need for amiloride after initial diuresis has been achieved 1
Monitoring Requirements
- Electrolytes: Monitor serum potassium within 2-4 weeks of initiating therapy and after dose changes
- Renal function: Regular monitoring is essential, especially in patients with renal impairment
- Blood pressure: Regular monitoring to assess efficacy
Contraindications and Cautions
- Renal impairment: Use with extreme caution or avoid in patients with significant renal dysfunction
- Hyperkalemia risk: Avoid in patients with serum potassium >5.0 mmol/L
- Combination therapy: Use with caution when combined with ACE inhibitors, ARBs, or other potassium-sparing diuretics due to increased risk of hyperkalemia 2
- Monotherapy: Amiloride should rarely be used alone as it has weak diuretic and antihypertensive effects compared to thiazides 1
Adverse Effects to Monitor
- Hyperkalemia: Most significant risk (approximately 10% with amiloride monotherapy) 1
- Acute kidney injury: Particularly when combined with other antihypertensive medications
- Metabolic effects: Generally favorable compared to thiazide diuretics alone
Clinical Pearls
- Amiloride blocks epithelial sodium channels (ENaC) in the distal tubule, which makes it particularly effective in conditions with pathological ENaC activation, such as nephrotic syndrome 5
- The combination of amiloride with hydrochlorothiazide at equipotent doses on blood pressure prevents glucose intolerance associated with thiazide monotherapy 3
- Even low doses of amiloride (2.5 mg) combined with hydrochlorothiazide (25 mg) can provide significant potassium-sparing effects 6
- Amiloride is excreted unmetabolized in urine and feces with a serum half-life of approximately 6 hours 7
By following these guidelines, amiloride can be effectively and safely used as part of hypertension and edema management, particularly when potassium conservation is a priority.