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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).
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.
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.
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).
Oral: Geriatric patients also show decreased clearance of amiloride: use with caution. Refer to adult dosing.
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)
Manufacturers 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).
There are no dosage adjustments provided in the manufacturer 's labeling; use with caution.
Administer with food or meals to avoid GI upset.
Do not use potassium-containing salt substitutes.
Store at 20 � �C to 25 � �C (68 � �F to 77 � �F). Avoid freezing or excessive heat. Protect from moisture.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Generic: 5 mg
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.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
I & O, daily weights, blood pressure, serum electrolytes, renal function; signs/symptoms of hyperkalemia
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
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.
B
Adverse events were not observed in animal reproduction studies.
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.
30% to 90% (Macfie 1981)
Vd: 350 to 380 L (Macfie 1981)
Does not undergo hepatic metabolism
Urine (~50%; as unchanged drug); feces (~40%)
Within 2 hours; Peak effect: 6 to 10 hours
Serum:3 to 4 hours
~24 hours
Normal renal function: 6 to 9 hours; renal impairment (CrCl <50 mL/minute): 21 to 144 hours (George 1980)
Minimal (Macfie 1981)
- 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, weak, shortness of breath, numbness or tingling feeling), severe nausea, vomiting, dry mouth, more 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.