MEDICATION SAFETY ISSUES
AMILoride may be confused with amiodarone, amLODIPine, amrinone
Diuretic, Potassium Sparing
DOSING: ADULTS — Hypertension, edema (to limit potassium loss): Oral: Initial: 5-10 mg/day (up to 20 mg)
Hypertension (JNC 7): 5-10 mg/day in 1-2 divided doses
DOSING: PEDIATRIC — Hypertension (unlabeled use): Children 1-17 years: Oral: 0.4-0.625 mg/kg/day (maximum: 20 mg/day)
(For additional information see “Amiloride: Pediatric drug information”)
DOSING: ELDERLY — Oral: Initial: 5 mg once daily or every other day
DOSING: RENAL IMPAIRMENT — Oral:
Clcr 10-50 mL/minute: Administer 50% of normal dose.
Clcr <10 mL/minute: Avoid use.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, as hydrochloride: 5 mg
DOSAGE FORMS: CONCISE
Tablet: 5 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer with food or meals to avoid GI upset.
USE — Counteracts potassium loss induced by other diuretics in the treatment of hypertension or edematous conditions including CHF, hepatic cirrhosis, and hypoaldosteronism; usually used in conjunction with more potent diuretics such as thiazides or loop diuretics
USE – UNLABELED / INVESTIGATIONAL — Investigational: Cystic fibrosis; reduction of lithium-induced polyuria; pediatric hypertension
ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Central nervous system: Headache, fatigue, dizziness
Endocrine & metabolic: Hyperkalemia (up to 10%; risk reduced in patients receiving kaliuretic diuretics), hyperchloremic metabolic acidosis, dehydration, hyponatremia, gynecomastia
Gastrointestinal: Nausea, diarrhea, vomiting, abdominal pain, gas pain, appetite changes, constipation
Neuromuscular & skeletal: Muscle cramps, weakness
Respiratory: Cough, dyspnea
<1% (Limited to important or life-threatening): Alopecia, arrhythmia, bladder spasms, chest pain, dyspnea, dysuria, GI bleeding, intraocular pressure increased, jaundice, orthostatic hypotension, palpitation, polyuria 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); anuria; acute or chronic renal insufficiency; evidence of diabetic nephropathy. Patients with evidence of renal impairment or diabetes mellitus should not receive this medicine without close, frequent monitoring of serum electrolytes and renal function.
WARNINGS / PRECAUTIONS
Boxed warnings: Hyperkalemia: See “Concerns related to adverse effects” below.
Concerns related to adverse effects: Fluid/electrolyte loss: Excess amounts can lead to profound diuresis with fluid and electrolyte loss; close medical supervision and dose evaluation are required. Watch for and correct electrolyte disturbances; adjust dose to avoid dehydration. Hyperkalemia: [U.S. Boxed Warning]: Hyperkalemia can occur; patients at risk include those with renal impairment, diabetes, the elderly, and the severely ill. Serum potassium levels must be monitored at frequent intervals especially when dosages are changed or with any illness that may cause renal dysfunction.
Disease-related concerns: Cirrhosis: In cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Diabetes: Use with extreme caution in patients with diabetes mellitus; monitor closely. Discontinue amiloride 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, uncontrolled diabetes).
Special populations: Pediatrics: Safety and efficacy have not been established in children.
ACE Inhibitors: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Ammonium Chloride: Potassium-Sparing Diuretics may enhance the adverse/toxic effect of Ammonium Chloride. Specifically the risk of systemic acidosis. Risk D: Consider therapy modification
Angiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: 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. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Drospirenone: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: 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. Risk D: Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Mitotane: Potassium-Sparing Diuretics may diminish the therapeutic effect of Mitotane. High dose diuretics (eg, Cushings syndrome) may present significantly higher risk than low doses (eg, CHF). Risk D: Consider therapy modification
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. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk D: Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
QuiNIDine: Potassium-Sparing Diuretics may diminish the therapeutic effect of QuiNIDine. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Tolvaptan: May enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Hyperkalemia may result if amiloride is taken with potassi
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies.
LACTATION — Excretion in breast milk unknown/not recommended
DIETARY CONSIDERATIONS — Take with food or meals to avoid GI upset. Do not use salt substitutes or low salt milk without checking with your healthcare provider; too much potassium can be as harmful as too little.
PRICING — (data from drugstore.com)
Tablets (Amiloride HCl)
5 mg (30): $50.45
5 mg (30): $25.99
MONITORING PARAMETERS — I & O, daily weights, blood pressure, serum electrolytes, renal function
CANADIAN BRAND NAMES — Apo-Amiloride®
INTERNATIONAL BRAND NAMES — Alverix (CY); Amiclaran (CZ); Amiduret Trom (DE); Amikal (DK); Amilamont (GB); Amilo (KP); Amilo 5 (KP); Amiloberag (DE); Amilorid NM Pharma (SE); Amilozid (HN); Amiride (IL); Berkamil (IE); Edepin (TW); Kaluril (AU, TW); Midamor (AT, CH, FI, GB, IE, NL, NO, NZ, SE); Modamide (FR); Moduretic (Combinado con hidroclorotiazida) (MX); Nirulid (DK); Pandiuren (AR); Puritrid (FI)
MECHANISM OF ACTION — Inhibits sodium reabsorption in the distal tubule, cortical collecting tubule, and collecting duct subsequently reducing both potassium and hydrogen excretion resulting in weak natriuretic, diuretic, and antihypertensive activity; increases sodium loss; increases potassium retention; decreases calcium excretion; decreases magnesium loss
PHARMACODYNAMICS / KINETICS
Onset of action: 2 hours
Duration: 24 hours
Absorption: ~15% to 25%
Distribution: Vd: 350-380 L
Protein binding: 23%
Metabolism: No active metabolites
Half-life elimination: Normal renal function: 6-9 hours; End-stage renal disease: 8-144 hours
Time to peak, serum: 6-10 hours
Excretion: Urine and feces (equal amounts as unchanged drug)
PATIENT INFORMATION — Report any muscle cramps, weakness, nausea, or dizziness. Use caution operating machinery or performing other tasks requiring alertness.