|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(a MIL oh ride)
Generic Available (U.S.)
Yes
Index Terms
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
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
Pregnancy Risk Factor
B
Pregnancy Considerations
Teratogenic effects were not observed in animal studies.
Lactation
Excretion in breast milk unknown/not recommended
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.
Adverse Reactions
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
Genitourinary: Impotence
Neuromuscular & skeletal: Muscle cramps, weakness
Respiratory: Cough, dyspnea
<1% (Limited to important or life-threatening): Orthostatic hypotension, arrhythmia, palpitation, chest pain, alopecia, GI bleeding, polyuria, bladder spasms, dysuria, jaundice, intraocular pressure increased, dyspnea
Drug Interactions
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
Dofetilide: AMILoride may increase the serum concentration of Dofetilide. 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
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: 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. 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
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. Risk D: Consider therapy modification
Tacrolimus: Potassium-Sparing Diuretics may enhance the hyperkalemic effect of Tacrolimus. Risk X: Avoid combination
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 potassium-containing foods.
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)
Dosage
Oral:
Children 1-17 years: Hypertension (unlabeled use): 0.4-0.625 mg/kg/day (maximum: 20 mg/day)
Adults: 5-10 mg/day (up to 20 mg)
Hypertension (JNC 7): 5-10 mg/day in 1-2 divided doses
Elderly: Initial: 5 mg once daily or every other day
Dosing adjustment in renal impairment:
Clcr 10-50 mL/minute: Administer at 50% of normal dose.
Clcr <10 mL/minute: Avoid use.
Administration: Oral
Administer with food or meals to avoid GI upset.
Monitoring Parameters
I & O, daily weights, blood pressure, serum electrolytes, renal function
Test Interactions
Increased potassium (S)
Dietary Considerations
Take with food or meals to avoid GI upset. Do not use salt substitutes or low salt milk without checking with healthcare provider.
Patient Education
Take early in day with food. Do not increase dietary intake of potassium unless instructed by prescriber. Report muscle cramping or weakness, unresolved nausea or vomiting, palpitations, or respiratory difficulty.
Geriatric Considerations
Use lower initial dose, and adjust dose for renal impairment.
Additional Information
Medication should be discontinued if potassium level exceeds 6.5 mEq/L. Combined with hydrochlorothiazide as Moduretic®. Amiloride is considered an alternative to triamterene or spironolactone.
Anesthesia and Critical Care Concerns/Other Considerations
Medication should be discontinued if hyperkalemia develops. Amiloride may cause hyperkalemia. The ECG manifestations may include peaked T waves, QRS prolongation, and cardiac conduction abnormalities.
Cardiovascular Considerations
Amiloride may cause hyperkalemia, the ECG manifestations of which include peaked T waves, QRS prolongation, and cardiac conduction abnormalities.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause drowsiness; rarely may cause insomnia and depression
Mental Health: Effects on Psychiatric Treatment
May cause impotence and orthostatic hypotension which may be exacerbated by psychotropics; effective agent for the treatment of lithium-induced diabetes insipidus
Nursing: Physical Assessment/Monitoring
Assess whether patient is at risk for hyperkalemia. Assess electrolytes and fluid status. Monitor for hyperkalemia.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral, as hydrochloride: 5 mg
Pricing: U.S. (www.drugstore.com)
Tablets (AMILoride HCl)
5 mg (30): $37.99
Tablets (Amiloride HCl)
5 mg (30): $50.45
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.
References
Chobanian AV, Bakris GL, Black HR, et al, “The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report,” JAMA, 2003, 289(19):2560-71.
Jaffey L and Martin A, “Malignant Hyperkalemia After Amiloride/Hydrochlorothiazide Treatment,” Lancet, 1981, 1(8232):1272.
Kleyman TR and Cragoe EJ Jr, “The Mechanism of Action of Amiloride,” Semin Nephrol, 1988, 8(3):242-8.
Lindenfeld J, Albert NM, Boehmer JP, et al, “HFSA 2010 Comprehensive Heart Failure Practice Guideline,” J Card Fail, 2010, 16(6):e1-194.
National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents, “The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents,” Pediatrics, 2004, 114(2 Suppl):555-76.
Wang L, Sheldon RS, Mitchell LB, et al, “Amiloride-Quinidine Interaction: Adverse Outcomes,” Clin Pharmacol Ther, 1994, 56(6 Pt 1):659-67.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
|
