What are the side effects of amiloride?

Side Effects of Amiloride

The most critical side effect of amiloride is hyperkalemia (serum potassium >5.5 mEq/L), which can be life-threatening, particularly when combined with ACE inhibitors, ARBs, or in patients with renal impairment. 1

Serious and Life-Threatening Side Effects

Hyperkalemia

• Severe hyperkalemia is the primary safety concern and occurs especially when amiloride is combined with ACE inhibitors or ARBs 2
• Risk is substantially increased in older patients, those with diabetes, chronic kidney disease, or concurrent NSAID use 2
• In one case report, amiloride addition to a regimen including ACEi and spironolactone caused dangerous hyperkalemia (potassium rising from 4.6 to 7.8 mmol/L) 3
• Close monitoring of serum potassium is mandatory, particularly within 5-7 days after initiation and with any dose changes 4

Acute Kidney Injury

• Acute kidney injury can occur, particularly when added to multiple antihypertensive medications 3
• In the nephrotic syndrome case, eGFR decreased from 41 to 29 mL/min after amiloride initiation 3

Common Side Effects (Incidence >1%)

Gastrointestinal

• Nausea/anorexia (3-8% of patients) 1
• Diarrhea (3-8% of patients) 1
• Vomiting (3-8% of patients) 1
• Abdominal pain and flatulence are frequently reported 1

Neurological

• Headache is common (>1% incidence) 1
• Dizziness occurs in a notable proportion of patients 1

Musculoskeletal

• Muscle cramps are reported in >1% of patients 1

Less Common Side Effects (Incidence ≤1%)

Cardiovascular

• Orthostatic hypotension 1
• Arrhythmia and palpitations 1
• Angina pectoris 1

Endocrine/Sexual

• Gynecomastia (though less common than with spironolactone) 1, 5
• Impotence and decreased libido 1

Dermatologic

• Skin rash (mild, probably related to amiloride) 1
• Pruritus and alopecia 1

Neuropsychiatric

• Encephalopathy 1
• Nervousness, mental confusion, and insomnia 1
• Paresthesia and tremors 1

Genitourinary

• Polyuria, dysuria, and urinary frequency 1
• Bladder spasms 1

Hematologic (Rare)

• Aplastic anemia and neutropenia have been reported, though causal relationship uncertain 1

Important Clinical Considerations

Advantages Over Other Potassium-Sparing Diuretics

• Amiloride has less anti-androgen effects than spironolactone, making it preferable in patients with tender gynecomastia 2
• Longer duration of action than triamterene, allowing once-daily dosing 5
• More benign side effect profile compared to spironolactone (no tumorigenicity or estrogenic effects) 5

Metabolic Effects

• Amiloride has magnesium-sparing properties in addition to potassium-sparing effects 6
• Can increase plasma renin activity and aldosterone levels, particularly in primary hyperaldosteronism 7

Dosing Context

• Typical dosing is 0.4-0.625 mg/kg/day in children, maximum 20 mg/day 2
• In adults with resistant hypertension, doses of 2.5-10 mg daily are effective 2
• Amiloride should be used at 1/10 the dose of spironolactone (e.g., 10-40 mg/day amiloride vs 100-400 mg/day spironolactone) 2

Critical Monitoring Requirements

• Electrolytes (particularly potassium) must be monitored shortly after initiating therapy and periodically thereafter 2
• Serum creatinine should be checked regularly to detect acute kidney injury 3
• More frequent monitoring is required when initiating therapy, changing doses, or in high-risk patients 4