Amiloride is a potassium-sparing diuretic that is available is a single drug and in combination with Furosemide (Lasoride).

Amiloride Uses:

• Heart failure or hypertension:

  • It aids in preventing potassium loss induced by other diuretics in the treatment of hypertension or heart failure usually used in combination with more potent diuretics such as thiazides/loop diuretics.

Note: Potassium-sparing diuretics are not recommended as first-line for treating hypertension. It is used concurrently with thiazide diuretics to prevent hypokalemia.

• Off Label Use of Amiloride in Adults:

  • Ascites

Amiloride dose in adults:

Amiloride dose for the treatment of hypertension and heart failure (as alternative medicine):

• Initial: 5 mg per oral once daily;
• titrate as needed to 10 mg daily in 1 or 2 divided doses;
• The dose may be increased in increments of 5 mg daily up to 20 mg in 1 or 2 divided doses.
• Usual dosage range in hypertension: 5 to 10 mg daily in 1 or 2 divided doses

Amiloride dose for the treatment of Ascites:

• Initial: 10 mg b.i.d daily.
• If no response, increase every 4 days in increments of 10 mg twice daily to a maximum dosage of 30-40 mg twice daily

Amiloride dose in children:

Amiloride dose for the treatment of Hypertension:

• Children and Adolescents:

  • Initial: 0.4 to 0.625 mg/kg per oral  once daily
  • The maximum daily dose is 20 mg/day

Amiloride dose for the treatment of Edema: 

• Children and Adolescents:

  • 0.625 mg/kg per oral per day divided every 12 to 24 hours
  • The maximum daily dose is 20 mg/day

Amiloride dose for the treatment of congenital Nephrogenic diabetes insipidus:

• Infants, Children, and Adolescents:

  • 0.3 mg/kg per oral per day in divided doses 3 times daily or 20 mg/1.73 m² /day in combination with hydrochlorothiazide.

Pregnancy Risk Factor B

• Studies on animal reproduction did not show any adverse outcomes.

Amiloride use during breastfeeding:

• It is not known if the drug is excreted in breastmilk.
• The possibility of serious adverse reactions in breastfeeding infants should be considered. It is important to consider the mother's needs.

Amiloride Dose adjustment in renal disease:

• Manufacturer's labeling:

  • Use of amiloride in patients with DM, creatinine >1.5 mg/dL, or BUN >30 mg/dL should be done with careful monitoring
  • It is contraindicated in patients with diabetic nephropathy,anuria, acute/chronic renal failure.

• Alternate recommendations:

  • Creatinine clearance 10 to 50 mL/minute:

    • A 50% dose reduction is required.
    • It should not be used in elderly ≥65 years of age with a creatinine clearance <30 mL/minute due to the risk of hyperkalemia and hyponatremia.

  • Creatinine clearance <10 mL/minute:

    • Should not be given.

Dose adjustment in liver disease:

There are no dosage adjustments provided in the manufacturer’s labeling. 

Side Effects of Amiloride:

• Central Nervous System:

  • Dizziness
  • Fatigue
  • Headache

• Endocrine & Metabolic:

  • Hyperkalemia
  • Dehydration
  • Gynecomastia
  • Hyperchloremic Metabolic Acidosis
  • Hyponatremia

• Gastrointestinal:

  • Abdominal Pain
  • Change In Appetite
  • Constipation
  • Diarrhea
  • Gas Pain
  • Nausea
  • Vomiting

• Genitourinary:

  • Impotence

• Neuromuscular & Skeletal:

  • Muscle Cramps
  • Weakness

• Respiratory:

  • Cough
  • Dyspnea

Contraindications to Amiloride:

• Hypersensitivity to amiloride and any component of the formulation
• Hyperkalemia>5.5 mEq/L
• Diabetic Nephropathy
• Anuria
• Chronic or acute renal insufficiency
• Concurrent therapy using potassium-sparing agents like triamterene, spironolactone and triamterene
• Potassium supplementation

Warnings and precautions·

• Fluid/electrolyte changes:

  • It can cause hyponatremia/hypochloremia therefore strict monitoring is required.

• Hyperkalemia: [US Boxed Warning]:

  • It can cause hyperkalemia, which manifests as muscle weakness, fatigue and flaccid paralysis, bradycardia or shock, and ECG abnormalities.
  • Risk factors include renal impairment, elderly people, DM, concurrent potassium sparing drugs, and those who are already on DM.
  • It is important to monitor closely and stop the drug immediately if hyperkalemia occurs.

• Insufficiency of the adrenals:

  • It should not be used to treat hypertension caused by Addison disease.

• Cirrhosis

  • Due to the possibility of hepatic disease, electrolyte imbalances and acid/base imbalances in cirrhosis should be considered.

• Diabetes:

  • Diabetes mellitus patients should avoid it.
  • You should stop it at least three days before you test your glucose tolerance.

• Respiratory and metabolic acidosis

  • Poorly controlled DM is dangerous for people who are at high risk of developing metabolic and respiratory acidosis, such as heart disease 

Amiloride: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• BP
• Daily weight
• Serum electrolytes
• Signs/symptoms of hyperkalemia.

How to administer Amiloride?

• It should be prescribed orally with food to prevent gastrointestinal complications.

Mechanism of action of Amiloride:

• It blocks sodium reabsorption through lumen by blocking epithelial sodium channel in the late distal convoluted tubeule and collecting conduit.
• This results in significant intracellular sodium loss and decreased function of the Na+/K+ATPase Pump.
• It also causes potassium retention and decreased excretion calcium, magnesium and hydrogen.
• Due to the limited sodium uptake capacity of the distal convoluted tube and collecting duct, the natriuretic/diuretic and antihypertensive effects can be considered weak.

The onset of action:

• Within 2 hours Peak effect: 6 to 10 hours

Duration:

• 24 hours

Absorption:

• 30% to 90%

Protein binding:

• Minimal

Metabolism:

• Does not undergo hepatic metabolism

Half-life elimination:

• Normal renal function: 6 to 9 hours Renal impairment (Creatinine clearance <50 mL/minute): 21 to 144 hours

Time to peak, serum:

• 3 to 4 hours

Excretion:

• Occurs in urine (50%; as unchanged drug) feces (40%).

Amiloride Brand Names (International):

• Alverix
• Amiclaran
• Amiduret Trom
• Amikal
• Amilamont
• Amilo
• Amiloberag
• Amilorid NM Pharma
• Amiloride
• Amilozid
• Amiride
• Berkamil
• Conserve
• Edepin
• Kaluril
• Midamor
• Modamide
• Nirulid
• Pandiuren
• Puritrid

Amiloride Brand Names in Pakistan:

No Brands Available in Pakistan.