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.
Edema: Limited data available: Children and Adolescents: Oral: 0.625 mg/kg/day divided every 12 to 24 hours; maximum daily dose: 20 mg/day (Ref).
Hypertension: Limited data available: Children and Adolescents: Oral: Initial: 0.4 to 0.625 mg/kg/dose once daily; maximum daily dose: 20 mg/day (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no pediatric specific dosage adjustments provided in the manufacturer's labeling; in adults, use is contraindicated in patients with anuria or acute or chronic kidney insufficiency.
There are no dosage adjustments in the manufacturer's labeling.
(For additional information see "Amiloride: Drug information")
Hypertension, chronic (alternative agent):
Note: Not recommended for initial management but may be considered as additional therapy in patients with resistant hypertension who do not respond adequately to optimal combination therapy with preferred agents. An aldosterone receptor antagonist (eg, spironolactone) is typically preferred for resistant hypertension that does not respond to preferred agents; amiloride is an alternative. May be used in patients who develop hypokalemia due to other diuretics (Ref).
Oral: Initial: 5 mg once daily; evaluate response after ~2 to 4 weeks and increase dose as needed to 10 mg daily in 1 or 2 divided doses (Ref).
Hypokalemia due to chronic stable renal potassium wasting (eg, certain tubulopathies, chronic kaliuretic diuretic use), treatment (off-label use):
Note: In patients with renal potassium wasting, amiloride may be more effective and better tolerated than oral potassium supplementation (Ref).
Oral: Initial: 5 to 10 mg once daily; if needed, may gradually increase dose (eg, every 1 to 2 weeks based on serum potassium monitoring) in 5 mg/day increments based on response and tolerability up to 40 mg/day (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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 (Ref). 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 (Ref). The 2017 guideline for the prevention, detection, evaluation, and management of high blood pressure in adults recommends avoiding use in patients with significant chronic kidney disease (eg, GFR <45 mL/minute) (Ref).
CrCl <10 mL/minute: Avoid use (Ref).
There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Cardiovascular: Angina pectoris (≤1%), cardiac arrhythmia (≤1%), chest pain (≤1%), orthostatic hypotension (≤1%), palpitations (≤1%)
Dermatologic: Alopecia (≤1%), pruritus (≤1%), skin rash (≤1%)
Endocrine & metabolic: Decreased libido (≤1%), gynecomastia (≤1%), hyperkalemia (~10%), increased thirst (≤1%)
Gastrointestinal: Abdominal pain (<3%), anorexia (≤8%), change in appetite (<3%), constipation (<3%), diarrhea (3% to 8%), dyspepsia (≤1%), flatulence (≤1%), gas pain (<3%), gastrointestinal distress (≤1%), gastrointestinal fullness (≤1%), gastrointestinal hemorrhage (≤1%), heartburn (≤1%), nausea (≤8%), vomiting (3% to 8%), xerostomia (≤1%)
Genitourinary: Bladder spasm (≤1%), dysuria (≤1%), erectile dysfunction (<3%), polyuria (≤1%), urinary frequency (≤1%)
Hepatic: Jaundice (≤1%)
Nervous system: Asthenia (<3%), confusion (≤1%), depression (≤1%), dizziness (<3%), drowsiness (≤1%), encephalopathy (<3%), fatigue (<3%), headache (3% to 8%), insomnia (≤1%), nervousness (≤1%), paresthesia (≤1%), tremor (≤1%), vertigo (≤1%)
Neuromuscular & skeletal: Arthralgia (≤1%), back pain (≤1%), limb pain (≤1%), lower extremity pain (≤1%), muscle cramps (<3%), neck and shoulder pain (≤1%)
Ophthalmic: Increased intraocular pressure (≤1%), visual disturbance (≤1%)
Otic: Tinnitus (≤1%)
Respiratory: Cough (<3%), dyspnea (≤3%), nasal congestion (≤1%)
Postmarketing:
Gastrointestinal: Peptic ulcer (exacerbation)
Hematologic & oncologic: Aplastic anemia, neutropenia
Hepatic: Abnormal liver function
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.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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:
• Adrenal insufficiency: Avoid use of diuretics for treatment of elevated blood pressure in patients with primary adrenal insufficiency (Addison disease). Adjustment of glucocorticoid/mineralocorticoid therapy and/or use of other antihypertensive agents is preferred to treat hypertension (Bornstein 2016; Inder 2015).
• 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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Generic: 5 mg
Yes
Tablets (aMILoride HCl Oral)
5 mg (per each): $0.23 - $1.29
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Midamor: 5 mg
1 mg/mL Oral Suspension
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.
Oral: Administer with food.
Oral: Administer with food or meals to avoid GI upset.
Store at 20°C to 25°C (68°F to 77°F). Avoid freezing or excessive heat. Protect from moisture.
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 (FDA approved in adults); has also been used for management of edema and congenital nephrogenic diabetes insipidus
AMILoride may be confused with amiodarone, amLODIPine, inamrinone
Beers Criteria: Diuretics are identified in the Beers Criteria as potentially inappropriate medications to be used with caution in patients 65 years and older due to the potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium concentration closely when initiating or adjusting the dose in older adults (Beers Criteria [AGS 2023]).
Substrate of MATE1/2-K, OCT2;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Aliskiren: Potassium-Sparing Diuretics may increase hyperkalemic effects of Aliskiren. Risk C: Monitor
Amifostine: Blood Pressure Lowering Agents may increase hypotensive effects of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider Therapy Modification
Ammonium Chloride: Potassium-Sparing Diuretics may increase adverse/toxic effects of Ammonium Chloride. Specifically the risk of systemic acidosis. Risk C: Monitor
Amphetamines: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Angiotensin II Receptor Blockers: Potassium-Sparing Diuretics may increase hyperkalemic effects of Angiotensin II Receptor Blockers. Risk C: Monitor
Angiotensin-Converting Enzyme Inhibitors: Potassium-Sparing Diuretics may increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor
Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Barbiturates: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Benperidol: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Brigatinib: May decrease antihypertensive effects of Antihypertensive Agents. Brigatinib may increase bradycardic effects of Antihypertensive Agents. Risk C: Monitor
Brimonidine (Topical): May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Bromperidol: May decrease hypotensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase hypotensive effects of Bromperidol. Risk X: Avoid
CycloSPORINE (Systemic): Potassium-Sparing Diuretics may increase hyperkalemic effects of CycloSPORINE (Systemic). Risk X: Avoid
Desmopressin: Hyponatremia-Associated Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor
Dexmethylphenidate: May decrease therapeutic effects of Antihypertensive Agents. Risk C: Monitor
Diacerein: May increase therapeutic effects of Diuretics. Specifically, the risk for dehydration or hypokalemia may be increased. Risk C: Monitor
Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Digitoxin: Potassium-Sparing Diuretics may increase adverse/toxic effects of Digitoxin. Potassium-Sparing Diuretics may decrease therapeutic effects of Digitoxin. Risk C: Monitor
Dofetilide: AMILoride may increase serum concentration of Dofetilide. Risk C: Monitor
Drospirenone-Containing Products: May increase hyperkalemic effects of Potassium-Sparing Diuretics. Risk C: Monitor
DULoxetine: Blood Pressure Lowering Agents may increase hypotensive effects of DULoxetine. Risk C: Monitor
Finerenone: Potassium-Sparing Diuretics may increase hyperkalemic effects of Finerenone. Risk C: Monitor
Flunarizine: May increase therapeutic effects of Antihypertensive Agents. Risk C: Monitor
Heparin: May increase hyperkalemic effects of Potassium-Sparing Diuretics. Risk C: Monitor
Heparins (Low Molecular Weight): May increase hyperkalemic effects of Potassium-Sparing Diuretics. Risk C: Monitor
Herbal Products with Blood Pressure Increasing Effects: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Hypotension-Associated Agents: Blood Pressure Lowering Agents may increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Iloperidone: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Indoramin: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Isocarboxazid: May increase hypotensive effects of Diuretics. Risk X: Avoid
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may increase hypotensive effects of Levodopa-Foslevodopa. Risk C: Monitor
Lithium: Potassium-Sparing Diuretics may decrease serum concentration of Lithium. Potassium-Sparing Diuretics may increase serum concentration of Lithium. Risk C: Monitor
Loop Diuretics: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Metergoline: May decrease antihypertensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase orthostatic hypotensive effects of Metergoline. Risk C: Monitor
Methylphenidate: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Molsidomine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicorandil: May increase hyperkalemic effects of Potassium-Sparing Diuretics. Risk C: Monitor
Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nitroprusside: Blood Pressure Lowering Agents may increase hypotensive effects of Nitroprusside. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents: May increase hyperkalemic effects of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may decrease antihypertensive effects of Potassium-Sparing Diuretics. Risk C: Monitor
Obinutuzumab: May increase hypotensive effects 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. Risk D: Consider Therapy Modification
Opioid Agonists: May increase adverse/toxic effects of Diuretics. Opioid Agonists may decrease therapeutic effects of Diuretics. Risk C: Monitor
Pentoxifylline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Perazine: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Pholcodine: Blood Pressure Lowering Agents may increase hypotensive effects of Pholcodine. Risk C: Monitor
Phosphodiesterase 5 Inhibitors: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Piperacillin: May increase hypokalemic effects of Diuretics. Risk C: Monitor
Polyethylene Glycol-Electrolyte Solution: Diuretics may increase nephrotoxic effects of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor
Potassium Salts: May increase hyperkalemic effects of AMILoride. Management: Amiloride and potassium supplements should not be used except in severe or refractory cases of hypokalemia. If coadministered, monitor serum potassium closely as rapid increases in potassium are possible. Risk D: Consider Therapy Modification
Potassium-Sparing Diuretics: May increase hyperkalemic effects of Potassium-Sparing Diuretics. Risk X: Avoid
Prazosin: Antihypertensive Agents may increase hypotensive effects of Prazosin. Risk C: Monitor
Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
QuiNIDine: AMILoride may increase adverse/toxic effects of QuiNIDine. AMILoride may decrease therapeutic effects of QuiNIDine. Risk C: Monitor
Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Sodium Phosphates: Diuretics may increase nephrotoxic effects of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor
Tacrolimus (Systemic): Potassium-Sparing Diuretics may increase hyperkalemic effects of Tacrolimus (Systemic). Risk C: Monitor
Terazosin: Antihypertensive Agents may increase hypotensive effects of Terazosin. Risk C: Monitor
Tolvaptan: May increase hyperkalemic effects of Potassium-Sparing Diuretics. Risk C: Monitor
Trimethoprim: May increase hyperkalemic effects of Potassium-Sparing Diuretics. Risk C: Monitor
Urapidil: Antihypertensive Agents may increase hypotensive effects of Urapidil. Risk C: Monitor
Do not use potassium-containing salt substitutes.
Medications considered acceptable for the treatment of chronic hypertension during pregnancy may generally be continued in patients trying to conceive. Diuretics are second-line agents for the treatment of hypertension in pregnant patients (ACC/AHA [Whelton 2018]; ACOG 2019; NICE 2019; SOGC [Magee 2022]).
Chronic maternal hypertension is associated with adverse events in the fetus/infant. Chronic maternal hypertension may increase the risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to the duration and severity of maternal hypertension. Untreated chronic hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, preeclampsia, delivery complications, stroke, and myocardial infarction (ACOG 2019; SOGC [Magee 2022]); however, data related to the use of amiloride during pregnancy are insufficient and other agents may be preferred (ESC [Regitz-Zagrosek 2018]).
Case reports describe the use of potassium-sparing diuretics such as amiloride for the adjunctive treatment of Gitleman syndrome during pregnancy (Calò 2012; Moustakakis 2012; Shahzad 2019). Use of amiloride may be considered in some pregnant patients for the treatment of primary aldosteronism (PA). Although data specific to the treatment of PA in pregnancy are limited, adjunctive therapy with amiloride may be initiated in the second or third trimester (ES [Funder 2016]; Forestiero 2022; Sanga 2022).
Serum potassium, sodium, creatinine, BUN, blood pressure, fluid balance
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.
Onset of action: Within 2 hours; Peak effect: 6 to 10 hours
Duration: ~24 hours
Absorption: 30% to 90% (Macfie 1981)
Distribution: Vd: 350 to 380 L (Macfie 1981)
Protein binding: Minimal (Macfie 1981)
Metabolism: Does not undergo hepatic metabolism
Half-life elimination: Normal renal function: 6 to 9 hours; Renal impairment (CrCl <50 mL/minute): 21 to 144 hours (George 1980)
Time to peak, serum: 3 to 4 hours
Excretion: Urine (~50%; as unchanged drug); feces (~40%)