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:

  • When taken in conjunction with stronger diuretics like thiazides or loop diuretics, it helps to minimise potassium loss caused by other diuretics in the treatment of hypertension or heart failure.

Note: Diuretics that spare potassium are not advised as the first line of treatment for hypertension. To avoid hypokalemia, thiazide diuretics are also used in conjunction with it.

• Off Label Use of Amiloride in Adults:

  • Ascites

Amiloride dose in adults:

Amiloride dose for treating hypertension and heart failure (as alternative medicine):

• Initial dose: 5 mg once daily by mouth; titrate as necessary to 10 mg daily in 1 or 2 divided doses; the dose may be raised in increments of 5 mg daily up to 20 mg daily in 1 or 2 divided doses.
• Usual dosage for hypertension is 5 to 10 mg daily, divided into 1 or 2 doses.

Amiloride dose for the treatment of Ascites:

• Initial: 10 mg b.i.d daily.
• If there is no improvement, gradually raise the dosage every 4 days by 10 mg twice daily, up to a maximum of 30–40 mg twice daily.

Amiloride dose in children:

Amiloride dose for the treatment of Hypertension:

• Children and Adolescents:

  • Initial: one daily oral dose of 0.4 to 0.625 mg/kg.
  • The maximum daily dose is 20 mg/day

Amiloride dose for the treatment of Edema: 

• Children and Adolescents:

  • 0.625 mg/kg divided into 12 to 24 oral doses each day
  • The daily dose cap is set at 20 mg.

Amiloride dose for the treatment of congenital Nephrogenic diabetes insipidus:

• Infants, Children, and Adolescents:

  • 0.3 mg/kg orally three times a day in divided dosages, or 20 mg/m2 per day when combined with hydrochlorothiazide

Pregnancy Risk Factor B

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

Amiloride use during breastfeeding:

• If the medication is excreted in breastmilk is unknown.
• 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:

  • Patients with diabetes mellitus (DM), creatinine >1.5 mg/dL, or BUN >30 mg/dL should use amiloride under close observation.
  • Patients with diabetic nephropathy, anuria, and acute or chronic renal failure should not use it.

• 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:

The manufacturer's labelling does not mention dosage modifications.

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.
  • If hyperkalemia develops, it's crucial to closely monitor and cease taking the medication very away.

• 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:

• CycloSPORINE Systemic's hyperkalemic effects may be exacerbated by potassium-sparing diuretics.
• This results in significant intracellular sodium loss and decreased function of the Na+/K+ATPase Pump.
• Spironolactone's hyperkalemic impact may be increased with AMILoride.
• It prevents sodium reabsorption via the lumen by obstructing the epithelial sodium channel in the collecting conduit and late distal convoluted tubeule.
• Additionally, it results in potassium retention and reduced calcium, magnesium, and hydrogen excretion.
• The distal convoluted tube and collecting duct's reduced ability to absorb sodium makes the natriuretic/diuretic and antihypertensive actions appear to be ineffective.

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:

• Normally functioning kidneys: 6 to 9 hours 21 to 144 hours for renal insufficiency (creatinine clearance 50 mL/minute).

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.