AMILORIDE HYDROCHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AMILORIDE HYDROCHLORIDE (AMILORIDE HYDROCHLORIDE).
Amiloride hydrochloride is a potassium-sparing diuretic that blocks epithelial sodium channels (ENaC) in the distal convoluted tubule and collecting duct of the nephron, inhibiting sodium reabsorption and reducing potassium and hydrogen ion secretion.
| Metabolism | Amiloride is not extensively metabolized; about 50% is excreted unchanged in urine and the remainder as inactive metabolites; metabolism occurs mainly in the liver via unknown pathways. |
| Excretion | Renal, approximately 50% unchanged; minor biliary/fecal elimination (<10%) |
| Half-life | Terminal elimination half-life is 6-9 hours; prolonged to 20-24 hours in renal impairment |
| Protein binding | Low, approximately 23-40% bound to plasma proteins |
| Volume of Distribution | 5-7 L/kg; indicates extensive tissue distribution |
| Bioavailability | Oral: 15-30% due to incomplete absorption (first-pass effect) |
| Onset of Action | Oral: 2 hours; diuresis peaks at 6-10 hours |
| Duration of Action | Oral: Approximately 24 hours; may persist up to 48 hours in renal impairment |
5-10 mg orally once daily; maximum 20 mg/day.
| Dosage form | TABLET |
| Renal impairment | eGFR 30-50 mL/min: reduce dose to 5 mg every other day; eGFR <30 mL/min: contraindicated. |
| Liver impairment | No dose adjustment required for Child-Pugh A or B; use caution in Child-Pugh C (no specific guidelines). |
| Pediatric use | 0.15-0.3 mg/kg/day orally divided once daily; maximum 10 mg/day. |
| Geriatric use | Initiate at 5 mg orally once daily; monitor renal function and electrolytes. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AMILORIDE HYDROCHLORIDE (AMILORIDE HYDROCHLORIDE).
| Breastfeeding | Amiloride is excreted into human breast milk in small amounts; the milk-to-plasma ratio is approximately 0.5. The drug is considered compatible with breastfeeding, but caution is advised due to the potential for adverse effects in the nursing infant, such as electrolyte imbalance. Use only if the expected benefit outweighs the potential risk to the infant. |
| Teratogenic Risk | Amiloride is classified as FDA Pregnancy Category B. Animal studies have not demonstrated fetal risk, but there are no adequate and well-controlled studies in pregnant women. It should be used during pregnancy only if clearly needed. Potential risks include electrolyte imbalances in the fetus due to maternal use, particularly in the second and third trimesters, but specific teratogenic effects are not established. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hyperkalemia (serum potassium >5.5 mEq/L)","Anuria","Acute or chronic renal insufficiency (e.g., CrCl <30 mL/min, serum creatinine >1.5 mg/dL in adults)","Diabetic nephropathy","Concomitant use with other potassium-sparing diuretics (e.g., spironolactone, eplerenone)","Concomitant use with potassium supplements","Hypersensitivity to amiloride or any component of the formulation"]
| Precautions | ["Hyperkalemia: risk increased in patients with renal impairment, diabetes, elderly, or those taking other potassium-sparing diuretics, potassium supplements, or ACE inhibitors","Monitor serum potassium and renal function regularly","Electrolyte imbalances: hyponatremia, hyperchloremic metabolic acidosis may occur","Risk of azotemia or hyperkalemia in patients with severe renal impairment (CrCl <30 mL/min)","Use caution with potassium-sparing drugs or potassium supplements"] |
| Food/Dietary | Avoid high-potassium foods (bananas, oranges, potatoes, tomatoes, spinach, avocados, dried fruits) in large quantities. Do not use potassium-containing salt substitutes. Concurrent use of ACE inhibitors, ARBs, or NSAIDs increases hyperkalemia risk. |
Loading safety data…
| Fetal Monitoring | Monitor maternal serum electrolytes (potassium, sodium, chloride), BUN, creatinine, and blood pressure. In pregnancy, monitor fetal growth and amniotic fluid volume if used for conditions like hypertension or edema. Assess for signs of maternal electrolyte disturbances which could affect the fetus. |
| Fertility Effects | Amiloride has not been associated with adverse effects on fertility in animal studies. No specific human data on fertility impairment; however, as a potassium-sparing diuretic, it may cause hormonal changes (e.g., increased aldosterone) that could indirectly affect reproductive function. Overall, no significant impact on fertility is reported. |
| Clinical Pearls | Amiloride is a potassium-sparing diuretic that inhibits epithelial sodium channels (ENaC) in the distal nephron. It is often used in combination with thiazide or loop diuretics to counteract potassium loss. Unlike spironolactone, it does not cause antiandrogenic side effects. Monitor serum potassium, especially in renal impairment or when used with ACE inhibitors/ARBs. Avoid in hyperkalemia and anuria. |
| Patient Advice | Take this medication exactly as prescribed, usually once daily with food. · Avoid potassium supplements or salt substitutes containing potassium without consulting your doctor. · Report symptoms of hyperkalemia such as muscle weakness, fatigue, irregular heartbeat, or tingling sensations. · This medication may cause dizziness; avoid driving until you know how it affects you. · Stay hydrated but do not increase potassium-rich foods excessively. |