Skip to Content

AMILoride

Pronunciation

Pronunciation

(a MIL oh ride)

Index Terms

  • Amiloride HCl
  • Amiloride Hydrochloride
  • Midamor

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as hydrochloride:

Generic: 5 mg

Pharmacologic Category

  • Antihypertensive
  • Diuretic, Potassium-Sparing

Pharmacology

Blocks epithelial sodium channels in the late distal convoluted tubule (DCT), and collecting duct which inhibits sodium reabsorption from the lumen. This effectively reduces intracellular sodium, decreasing the function of Na+/K+ATPase, leading to potassium retention and decreased calcium, magnesium, and hydrogen excretion. As sodium uptake capacity in the DCT/collecting duct is limited, the natriuretic, diuretic, and antihypertensive effects are generally considered weak.

Absorption

30% to 90% (Macfie 1981)

Distribution

Vd: 350 to 380 L (Macfie 1981)

Metabolism

Does not undergo hepatic metabolism

Excretion

Urine (~50%; as unchanged drug); feces (~40%)

Onset of Action

Within 2 hours; Peak effect: 6 to 10 hours

Time to Peak

Serum:3 to 4 hours

Duration of Action

~24 hours

Half-Life Elimination

Normal renal function: 6 to 9 hours; renal impairment (CrCl <50 mL/minute): 21 to 144 hours (George 1980)

Protein Binding

Minimal (Macfie 1981)

Use: Labeled Indications

Heart failure or hypertension: Counteracts potassium loss induced by other diuretics in the treatment of hypertension or heart failure; usually used in conjunction with more potent diuretics such as thiazides or loop diuretics

According to the Eighth Joint National Committee (JNC 8) guidelines, potassium-sparing diuretics are not recommended for the initial treatment of hypertension (James, 2013). The American Society of Hypertension/International Society of Hypertension (ASH/ISH) suggests that amiloride in combination with other diuretics (eg, hydrochlorothiazide) may be used to prevent hypokalemia associated with diuretics used to manage hypertension (Weber, 2014).

Use: Unlabeled

Cystic fibrosis; reduction of lithium-induced polyuria; pediatric hypertension

Contraindications

Hypersensitivity to amiloride or any component of the formulation; presence of elevated serum potassium levels (>5.5 mEq/L); if patient is receiving other potassium-conserving agents (eg, spironolactone, triamterene) or potassium supplementation (medicine, potassium-containing salt substitutes, potassium-rich diet) except in severe and/or refractory cases of hypokalemia; anuria; acute or chronic renal insufficiency; evidence of diabetic nephropathy. Patients with evidence of renal impairment (blood urea nitrogen [BUN] >30 mg/dL or serum creatinine >1.5 mg/dL) or diabetes mellitus should not receive amiloride without close, frequent monitoring of serum electrolytes and renal function.

Dosing: Adult

Hypertension, heart failure (to limit potassium loss): Oral: Initial: 5 mg once daily; may increase to 10 mg daily if necessary; doses >10 mg daily are usually not necessary; however, if patient is persistently hypokalemic, the dose may be increased in increments of 5 mg daily up to 20 mg daily with careful monitoring of electrolytes.

Ascites (off-label use): Initial: 10 mg twice daily. If no response, increase every 4 days in increments of 10 mg twice daily to a maximum dosage of 30 mg twice daily (Angeli 1994). American Association for the Study of Liver Diseases (AASLD) guidelines recommend a dosage range of 10 to 40 mg daily (AASLD [Runyon 2012]; EASL 2010).

Dosing: Geriatric

Oral: Geriatric patients also show decreased clearance of amiloride: use with caution. Refer to adult dosing.

Dosing: Pediatric

Hypertension (off-label use): Children and Adolescents 1 to 17 years: Oral: 0.4 to 0.625 mg/kg/day (maximum: 20 mg daily) (NHBPEP 2004)

Dosing: Renal Impairment

Manufacturer's labeling: Use of amiloride in patients with diabetes mellitus, SCr >1.5 mg/dL, or BUN >30 mg/dL should be done with caution and careful monitoring; use is contraindicated in patients with anuria, acute or chronic renal insufficiency, or evidence of diabetic nephropathy.

Alternate recommendations:

CrCl 10 to 50 mL/minute: Administer at 50% of normal dose (Aronoff 2007). The Beers Criteria recommends avoiding use in older adults ≥65 years of age with a CrCl <30 mL/minute due to the risk of hyperkalemia and hyponatremia (Beers Criteria [AGS 2015]).

CrCl <10 mL/minute: Avoid use (Aronoff 2007).

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Extemporaneously Prepared

A 1 mg/mL oral suspension may be made with tablets. Crush ten 5 mg tablets in a mortar and reduce to a fine powder. Add small proportions up to 20 mL of Glycerin BP or Glycerin, USP and mix to uniform paste; mix while adding sterile water in incremental proportions to almost 50 mL; transfer to a calibrated bottle, rinse mortar with sterile water, and add quantity of sterile water sufficient to make 50 mL. Label “shake well” and “refrigerate”. Stable for 21 days.

Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.

Administration

Administer with food or meals to avoid GI upset.

Dietary Considerations

Do not use potassium-containing salt substitutes.

Storage

Store at 20°C to 25°C (68°F to 77°F). Avoid freezing or excessive heat. Protect from moisture.

Drug Interactions

ACE Inhibitors: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Ammonium Chloride: Potassium-Sparing Diuretics may enhance the adverse/toxic effect of Ammonium Chloride. Specifically the risk of systemic acidosis. Consider therapy modification

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Analgesics (Opioid): May enhance the adverse/toxic effect of Diuretics. Analgesics (Opioid) may diminish the therapeutic effect of Diuretics. Monitor therapy

Angiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

BuPROPion: May increase the serum concentration of OCT2 Substrates. Monitor therapy

Canagliflozin: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Canagliflozin may enhance the hypotensive effect of Potassium-Sparing Diuretics. Monitor therapy

Cardiac Glycosides: Potassium-Sparing Diuretics may diminish the therapeutic effect of Cardiac Glycosides. In particular, the inotropic effects of digoxin appear to be diminished. Potassium-Sparing Diuretics may increase the serum concentration of Cardiac Glycosides. This particular effect may be unique to Spironolactone. Monitor therapy

CycloSPORINE (Systemic): Potassium-Sparing Diuretics may enhance the hyperkalemic effect of CycloSPORINE (Systemic). Avoid combination

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Dofetilide: AMILoride may increase the serum concentration of Dofetilide. Monitor therapy

Drospirenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Eplerenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: This combination is contraindicated in patients receiving eplerenone for treatment of hypertension. Consider therapy modification

Heparin: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: Monitor serum potassium concentrations closely. The spironolactone Canadian product monograph lists its combination with heparin or low molecular weight heparins as contraindicated. Monitor therapy

Heparin (Low Molecular Weight): May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: Monitor serum potassium concentrations closely. The spironolactone Canadian product monograph lists its combination with heparin or low molecular weight heparins as contraindicated. Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Potassium Salts: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Consider therapy modification

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

QuiNIDine: Potassium-Sparing Diuretics may diminish the therapeutic effect of QuiNIDine. Monitor therapy

Sodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with diuretics, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, hydrate adequately and monitor fluid and renal status. Consider therapy modification

Spironolactone: AMILoride may enhance the hyperkalemic effect of Spironolactone. Avoid combination

Tacrolimus (Systemic): Potassium-Sparing Diuretics may enhance the hyperkalemic effect of Tacrolimus (Systemic). Avoid combination

Tolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Adverse Reactions

1% to 10%:

Central nervous system: Dizziness, fatigue, headache

Endocrine & metabolic: Hyperkalemia (up to 10%; risk reduced in patients receiving kaliuretic diuretics), 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

<1% (Limited to important or life-threatening): Bladder spasm, cardiac arrhythmia, chest pain, dysuria, gastrointestinal hemorrhage, increased intraocular pressure, jaundice, orthostatic hypotension, palpitations, polyuria

ALERT: U.S. Boxed Warning

Hyperkalemia:

Like other potassium-conserving agents, amiloride may cause hyperkalemia (serum potassium levels greater than 5.5 mEq per liter) which, if uncorrected, is potentially fatal. Hyperkalemia occurs commonly (about 10%) when amiloride is used without a kaliuretic diuretic. This incidence is greater in patients with renal impairment, diabetes mellitus (with or without recognized renal insufficiency), and in the elderly. When amiloride is used concomitantly with a thiazide diuretic in patients without these complications, the risk of hyperkalemia is reduced to about 1% to 2%. It is thus essential to monitor serum potassium levels carefully in any patient receiving amiloride, particularly when it is first introduced, at the time of diuretic dosage adjustments, and during any illness that could affect renal function.

Warnings/Precautions

Concerns related to adverse effects:

• Fluid/electrolyte changes: May decrease sodium and chloride and increase BUN, especially with concomitant diuretic therapy; close medical supervision and dose evaluation are required. Watch for and correct electrolyte disturbances; adjust dose to avoid dehydration.

• Hyperkalemia: [US Boxed Warning]: Hyperkalemia (serum potassium levels >5.5 mEq/L) may occur, which can be fatal if not corrected; patients at higher risk include those with renal impairment, diabetes, and the elderly. Serum potassium levels must be monitored at frequent intervals especially when therapy is initiated, when dosages are changed or with any illness that may cause renal dysfunction. Risk of hyperkalemia may be increased when used concomitantly with other medications that may increase potassium (eg, angiotensin agents). Signs/symptoms of hyperkalemia include paresthesias, muscle weakness, fatigue, flaccid paralysis of limbs, bradycardia, shock, and ECG abnormalities. If hyperkalemia occurs, discontinue amiloride immediately and manage hyperkalemia as clinically appropriate.

Disease-related concerns:

• Cirrhosis: In cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy.

• Diabetes: If possible, avoid use in patients with diabetes mellitus; if cannot be avoided, use with extreme caution and monitor electrolytes and renal function closely. Discontinue amiloride at least 3 days prior to glucose tolerance testing.

• Metabolic/respiratory acidosis: Use with caution in patients who are at risk for metabolic or respiratory acidosis (eg, cardiopulmonary disease, poorly controlled diabetes); monitor acid base balance frequently.

• Renal impairment: Amiloride is primarily eliminated renally; patients with renal impairment are at greater risk for toxicities.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Monitoring Parameters

I & O, daily weights, blood pressure, serum electrolytes, renal function; signs/symptoms of hyperkalemia

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience diarrhea, headache, loss of strength and energy, dizziness, or lack of appetite. Have patient report immediately to prescriber signs of high potassium (abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, numbness or tingling feeling), severe nausea, vomiting, dry mouth, increased thirst, bradycardia, or muscle pain (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Hide