Loading...
Loading...
Medical Disclaimer: This information is for educational purposes only and is not a substitute for professional medical advice.
Thiazide Diuretic [EPC]
Amiloride is a potassium-sparing diuretic used primarily to treat hypertension and congestive heart failure, often in combination with other medications to prevent low potassium levels. It works by inhibiting sodium reabsorption in the kidneys.
Name
Amiloride
Raw Name
AMILORIDE HYDROCHLORIDE
Category
Thiazide Diuretic [EPC]
Salt Form
Hydrochloride
Drug Count
3
Variant Count
3
Last Verified
February 17, 2026
RxCUI
977880, 977883
UNII
FZJ37245UC, 0J48LPH2TH, 7DZO8EB0Z3, 7S82P3R43Z, 6XEF22AHC3, 08A7Y81S1P, 5405K23S50, 27O7W4T232, L0PFEMQ1DT
About Amiloride
Amiloride is a potassium-sparing diuretic used primarily to treat hypertension and congestive heart failure, often in combination with other medications to prevent low potassium levels. It works by inhibiting sodium reabsorption in the kidneys.
Detailed information about Amiloride
This page is for informational purposes only and does not replace medical advice. Consult a qualified healthcare professional before using any medication containing Amiloride.
Amiloride hydrochloride is a potent antikaliuretic (potassium-sparing) diuretic agent that belongs to the pyrazine-carbonyl-guanidine chemical class. Unlike many other diuretics that cause the body to lose potassium, amiloride is specifically designed to conserve potassium while promoting the excretion of sodium and water. It was first approved by the U.S. Food and Drug Administration (FDA) in 1981 under the brand name Midamor. While it possesses independent natriuretic (sodium-excreting) and antihypertensive properties, its clinical utility is most frequently realized when used as an adjunctive therapy. Healthcare providers typically prescribe amiloride alongside thiazide diuretics (like hydrochlorothiazide) or loop diuretics (like furosemide) to counteract the potassium-wasting effects of those medications. This dual approach helps maintain electrolyte balance in patients being treated for conditions such as essential hypertension (high blood pressure) or congestive heart failure.
Amiloride is unique because it is not an aldosterone antagonist (like spironolactone). Instead, it exerts its effects directly on the transport mechanisms within the kidney. Because it does not rely on blocking hormonal pathways, its onset of action is generally faster than that of aldosterone-targeting drugs. In contemporary medicine, amiloride remains a critical tool for managing patients who are prone to hypokalemia (dangerously low potassium levels) or those who have developed resistance to other diuretic therapies. Your healthcare provider will determine if amiloride is appropriate based on your renal function and baseline electrolyte levels.
To understand how amiloride works, one must look at the microscopic structures of the kidney known as nephrons. Specifically, amiloride targets the distal convoluted tubule and the cortical collecting duct. At the molecular level, amiloride acts as a highly selective blocker of the Epithelial Sodium Channels (ENaC). These channels are located on the luminal membrane (the side facing the urine) of the principal cells in the late distal tubule.
Under normal physiological conditions, sodium ions flow from the urine into these cells through ENaC. This movement of positively charged sodium creates an electrochemical gradient that encourages potassium ions to move out of the cell and into the urine to be excreted. By blocking the ENaC, amiloride prevents sodium from entering the cell. This action effectively 'shuts down' the electrical drive that would otherwise push potassium out of the body. Consequently, sodium and its associated water molecules remain in the urine to be excreted, while potassium is retained in the bloodstream. This mechanism is entirely independent of aldosterone, meaning amiloride can work even in states where aldosterone levels are low or suppressed. This direct inhibition makes amiloride a precise tool for fine-tuning the body's fluid and electrolyte balance.
Amiloride is incompletely absorbed from the gastrointestinal tract following oral administration. Clinical studies indicate that its bioavailability (the fraction of the drug that reaches systemic circulation) ranges from approximately 15% to 25%. When taken with food, the peak serum concentration (Cmax) may be slightly reduced, but the overall extent of absorption is not significantly altered. Peak plasma levels are typically reached within 3 to 4 hours after ingestion.
Amiloride has a relatively low level of plasma protein binding, estimated at roughly 23%. This means the majority of the drug circulates in its free, active form. It is widely distributed throughout the body, though it does not appear to cross the blood-brain barrier in significant amounts, which minimizes central nervous system side effects.
One of the most distinct features of amiloride is that it undergoes virtually no hepatic (liver) metabolism. Unlike many other drugs that are broken down by the CYP450 enzyme system, amiloride remains chemically unchanged as it circulates through the body. This makes it a preferred option for patients with liver disease, provided their kidney function is stable.
The primary route of elimination for amiloride is renal excretion. Approximately 50% of an oral dose is excreted unchanged in the urine within 48 hours. The remaining portion is excreted in the feces, likely representing unabsorbed drug. The terminal half-life of amiloride ranges from 6 to 9 hours, although this can be significantly prolonged in patients with renal impairment.
Amiloride is most commonly available in the following form:
In many regions, it is also available as a fixed-dose combination tablet, most notably Amiloride 5 mg / Hydrochlorothiazide 50 mg, which simplifies the dosing regimen for patients requiring both a potassium-sparing and a thiazide diuretic.
> Important: Only your healthcare provider can determine if Amiloride is right for your specific condition. Regular blood tests are required to monitor your response to this medication.
The dosage of amiloride is highly individualized based on the patient's clinical response and serum potassium levels.
The safety and effectiveness of amiloride in children have not been established through large-scale clinical trials. Consequently, there is no standardized FDA-approved pediatric dosage. In rare cases, such as Liddle's Syndrome, a pediatric nephrologist may prescribe amiloride using weight-based calculations, but this is considered 'off-label' and requires extreme caution and frequent monitoring of electrolyte levels.
Amiloride is primarily excreted by the kidneys. In patients with significant renal impairment (creatinine clearance less than 30-50 mL/min), the drug can accumulate rapidly, leading to life-threatening hyperkalemia. Amiloride is contraindicated in patients with anuria (no urine production) or acute renal failure. For those with mild to moderate impairment, lower doses and weekly potassium monitoring are mandatory.
Because amiloride is not metabolized by the liver, dose adjustments based solely on liver function are generally not required. However, patients with severe hepatic cirrhosis are at risk for metabolic alkalosis and electrolyte shifts, so amiloride should be used with caution in this population.
Older adults are more likely to have reduced renal function and may be taking other medications (like ACE inhibitors) that increase potassium. Healthcare providers typically start elderly patients on the lowest possible dose (e.g., 2.5 mg or 5 mg every other day) and monitor serum electrolytes frequently.
If you miss a dose of amiloride, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not double the dose to catch up, as this significantly increases the risk of potassium toxicity.
An overdose of amiloride primarily manifests as an exaggeration of its pharmacological effects, most notably severe hyperkalemia.
If an overdose is suspected, seek emergency medical attention immediately. Treatment in a hospital setting may include intravenous calcium gluconate to protect the heart, intravenous glucose and insulin to shift potassium into cells, or the use of cation-exchange resins (like sodium polystyrene sulfonate) to remove potassium from the body. In severe cases, hemodialysis may be required.
> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop taking the medication without medical guidance, as this can lead to dangerous fluctuations in your potassium levels.
While amiloride is generally well-tolerated when used at recommended doses, some patients may experience mild to moderate side effects as their body adjusts to the medication. Common side effects include:
These side effects occur in a smaller percentage of the population but should still be reported to a healthcare provider:
> Warning: Stop taking Amiloride and call your doctor immediately or seek emergency care if you experience any of the following:
With prolonged use of amiloride, the primary concern is the chronic management of electrolyte balance. Over months or years, patients may develop:
Amiloride carries a significant risk of developing hyperkalemia (high serum potassium levels, >5.5 mEq/L). This risk is particularly high in patients with renal impairment, diabetes mellitus, and in the elderly. If hyperkalemia occurs, it can lead to fatal cardiac arrhythmias. Potassium levels must be monitored frequently, especially when starting the drug, changing the dose, or during any illness that could affect kidney function. Amiloride should be discontinued immediately if potassium levels rise above the normal range.
Report any unusual symptoms to your healthcare provider. Regular laboratory monitoring is the only way to ensure that amiloride is working safely within your body.
Amiloride is a potent medication that requires careful medical supervision. The most critical safety consideration is the maintenance of potassium balance. Because amiloride prevents the kidneys from excreting potassium, levels can rise quickly to dangerous levels. Patients must be aware that hyperkalemia can be asymptomatic (showing no symptoms) until it causes a life-threatening heart rhythm problem. Therefore, adhering to all scheduled blood tests is non-negotiable for safety.
Amiloride hydrochloride can cause abnormally high serum potassium levels (hyperkalemia), which can be fatal. Hyperkalemia is most likely to occur in patients with renal impairment, diabetes (even without evidence of diabetic nephropathy), and in elderly or severely ill patients. Serum potassium levels must be monitored extremely closely in all patients receiving amiloride, particularly at the initiation of therapy and during dose adjustments. If serum potassium exceeds 5.5 mEq/L, amiloride should be discontinued immediately and appropriate measures taken to lower the potassium level.
While rare, hypersensitivity reactions can occur. Patients with a known allergy to amiloride or any component of the tablet should not take this medication. Signs of a reaction include skin rash, itching, and in severe cases, anaphylaxis.
Amiloride is contraindicated in patients with significant renal dysfunction. In patients with borderline renal function, amiloride can cause a further increase in Blood Urea Nitrogen (BUN) and creatinine. If the BUN rises above 30 mg/dL or creatinine rises above 1.5 mg/dL, the drug should be stopped unless the provider determines the benefit outweighs the risk.
Amiloride may induce or worsen hyperchloremic metabolic acidosis, particularly in patients with hepatic cirrhosis or diabetes. This occurs because the drug inhibits the secretion of hydrogen ions in the distal tubule. Your doctor may monitor your blood pH and bicarbonate levels if you are at risk.
Patients with diabetes are at a significantly higher risk of hyperkalemia when taking amiloride. Even those without diagnosed kidney disease may have 'subclinical' renal issues that make potassium clearance difficult. Glucose tolerance may also be slightly altered by diuretic therapy.
If you are prescribed amiloride, your healthcare provider will require regular laboratory monitoring, typically consisting of:
Amiloride can cause dizziness or fatigue, particularly during the first few days of treatment or when the dose is increased. Do not drive, operate heavy machinery, or engage in hazardous activities until you know how this medication affects you. If you feel lightheaded, sit or lie down immediately.
Alcohol can exacerbate the blood-pressure-lowering effects of amiloride, potentially leading to severe dizziness, fainting, or orthostatic hypotension. It is generally advised to limit or avoid alcohol consumption while taking diuretics.
Do not stop taking amiloride suddenly without consulting your doctor. If you have been taking it to manage heart failure or high blood pressure, stopping abruptly can lead to a rapid return of fluid retention or a 'rebound' spike in blood pressure. If the drug must be stopped due to high potassium, your doctor will provide specific instructions on how to safely transition to another therapy.
> Important: Discuss all your medical conditions, especially kidney disease, diabetes, and heart problems, with your healthcare provider before starting Amiloride.
Certain medications should never be used in combination with amiloride because the risk of life-threatening hyperkalemia is too high:
Drugs like lisinopril, enalapril, losartan, and valsartan also cause the body to retain potassium. While they are often used with diuretics for heart failure, the combination with amiloride requires very frequent blood monitoring. The clinical consequence is a high risk of severe hyperkalemia.
Common over-the-counter drugs like ibuprofen (Advil, Motrin) and naproxen (Aleve) can reduce the effectiveness of amiloride. More importantly, NSAIDs can decrease blood flow to the kidneys, which, when combined with amiloride, significantly increases the risk of acute kidney injury and hyperkalemia.
These immunosuppressants used in organ transplants can cause renal dysfunction and hyperkalemia. Combining them with amiloride is generally avoided unless under the strict supervision of a specialist.
Amiloride therapy may interfere with the measurement of serum magnesium levels and may cause a transient increase in BUN, serum creatinine, and uric acid levels. It does not typically interfere with standard urine drug screens.
> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking. Even 'natural' products can have serious interactions with amiloride.
Amiloride must NEVER be used in the following circumstances:
In these cases, a healthcare provider must perform a careful risk-benefit analysis:
There is no documented cross-sensitivity between amiloride and sulfonamide-derived diuretics (like hydrochlorothiazide or furosemide). However, patients who have had severe reactions to other pyrazine-class drugs should be monitored closely for potential cross-reactivity.
> Important: Your healthcare provider will evaluate your complete medical history, including recent blood work, before prescribing Amiloride to ensure it is safe for you.
Studies in animals (rabbits and mice) using doses up to 20 times the human dose have not shown evidence of harm to the fetus or impaired fertility. However, there are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, amiloride should be used during pregnancy only if clearly needed. It is important to note that diuretics are not generally recommended for the treatment of gestational edema or hypertension during pregnancy, as they can reduce placental perfusion (blood flow to the baby).
It is not known whether amiloride is excreted in human breast milk. However, studies in animals have shown that amiloride is excreted in rat milk in high concentrations. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Amiloride is not FDA-approved for use in pediatric patients. The safety and effectiveness in children have not been established. In clinical practice, its use in children is restricted to specialized settings (such as pediatric nephrology) for the treatment of rare conditions like Liddle’s Syndrome. In these cases, the risk of hyperkalemia is even more acute, and dosing must be managed with extreme precision.
Clinical studies of amiloride did not include sufficient numbers of subjects aged 65 and over to determine if they respond differently than younger subjects. However, it is well-known that elderly patients are at a significantly higher risk of developing hyperkalemia. This is due to the natural age-related decline in the Glomerular Filtration Rate (GFR) and a higher prevalence of co-morbidities like diabetes and heart failure. Geriatric patients are also more likely to be taking 'interacting' drugs like ACE inhibitors. Dosing in the elderly should be cautious, usually starting at the low end of the dosing range.
Amiloride is contraindicated in patients with moderate to severe renal impairment. For those with mild impairment, the drug's half-life is significantly prolonged (from 6-9 hours up to 30+ hours). This leads to a high risk of 'stacking' doses, where the drug builds up in the system faster than it can be cleared. If amiloride is used in this population, the dosing interval may need to be extended (e.g., every other day), and potassium levels must be checked weekly.
In patients with pre-existing hepatic disease, amiloride does not require a dose adjustment based on metabolism (since the liver doesn't break it down). However, these patients are at risk for hepatic encephalopathy if their electrolytes shift too quickly. Amiloride should be used with caution in patients with hepatic cirrhosis and ascites, as they are already prone to electrolyte imbalances and metabolic acidosis.
> Important: Special populations require individualized medical assessment. Always inform your doctor if you are pregnant, planning to become pregnant, or have any history of kidney or liver disease.
Amiloride is a pyrazine-carbonyl-guanidine that acts as a potent and selective inhibitor of the Epithelial Sodium Channel (ENaC). Unlike spironolactone, which is a competitive antagonist of the mineralocorticoid receptor, amiloride acts directly on the ion channels located on the apical membrane of the principal cells in the late distal convoluted tubule and the cortical collecting duct of the nephron. By plugging the pore of the ENaC, amiloride prevents the reabsorption of sodium ions (Na+) from the tubular lumen into the cell. This inhibition of sodium entry hyperpolarizes the apical membrane, which reduces the lumen-negative transepithelial potential difference. This electrical change removes the driving force for the secretion of potassium ions (K+) and hydrogen ions (H+) into the urine. Therefore, amiloride effectively 'spares' potassium and acid while promoting the loss of sodium and water.
The onset of the antikaliuretic (potassium-sparing) action of amiloride is usually seen within 2 hours after an oral dose. The peak effect occurs between 6 and 10 hours, and the duration of action lasts for approximately 24 hours. The dose-response relationship is relatively flat; increasing the dose beyond 10-20 mg does not significantly increase the natriuretic effect but does significantly increase the risk of hyperkalemia. Tolerance to the potassium-sparing effect does not typically develop with long-term use.
| Parameter | Value |
|---|---|
| Bioavailability | 15% - 25% |
| Protein Binding | ~23% |
| Half-life | 6 - 9 hours (Normal renal function) |
| Tmax (Time to Peak) | 3 - 4 hours |
| Metabolism | None (Excreted unchanged) |
| Excretion | Renal: ~50%; Fecal: ~40% |
Amiloride is classified as a Potassium-Sparing Diuretic. It is distinct from other diuretics like Thiazides (which act on the early distal tubule) and Loop Diuretics (which act on the Thick Ascending Limb of the Loop of Henle). Because it targets a more distal segment of the nephron, its sodium-clearing power is weaker than loop diuretics, but its ability to modulate potassium is much stronger.
Medications containing this ingredient
Common questions about Amiloride
Amiloride is primarily used as a potassium-sparing diuretic to treat high blood pressure (hypertension) and fluid retention (edema) caused by conditions like heart failure or cirrhosis. It is unique because, unlike most diuretics, it helps the body retain potassium while still getting rid of excess salt and water. Most often, it is prescribed in combination with other diuretics, such as hydrochlorothiazide or furosemide, specifically to prevent those drugs from causing dangerously low potassium levels. It is also the treatment of choice for a rare genetic condition called Liddle's Syndrome. Your healthcare provider will determine if it is necessary for your specific electrolyte balance.
The most common side effects of amiloride include headache, nausea, loss of appetite, and mild stomach discomfort. Some patients also report feeling fatigued or dizzy, especially when first starting the medication or when standing up quickly. Because it changes how your kidneys handle fluids, you might also experience changes in bowel habits, such as diarrhea or constipation. While these are often mild, they should be discussed with your doctor if they persist. The most serious side effect is hyperkalemia (high potassium), which requires regular blood tests to detect before it becomes dangerous.
It is generally recommended to limit or avoid alcohol while taking amiloride. Alcohol can significantly increase the blood-pressure-lowering effects of the medication, which may lead to severe dizziness, lightheadedness, or even fainting (orthostatic hypotension). Furthermore, alcohol can contribute to dehydration, which puts extra strain on the kidneys while they are being affected by the diuretic. If you choose to drink, do so in moderation and only after discussing it with your healthcare provider. Always be aware of how you feel when standing up after consuming alcohol while on this medication.
Amiloride is classified as FDA Pregnancy Category B, meaning animal studies haven't shown a risk, but there aren't enough high-quality studies in humans to guarantee safety. It should only be used during pregnancy if your doctor decides the benefits clearly outweigh the potential risks to the fetus. Generally, diuretics are avoided during pregnancy because they can reduce the volume of blood flowing to the placenta. If you are pregnant or planning to become pregnant, you must discuss alternative ways to manage your blood pressure or edema with your obstetrician. Breastfeeding is also generally discouraged while taking amiloride as its excretion into human milk is not fully understood.
Amiloride begins to affect your electrolyte and fluid balance relatively quickly, usually within 2 hours of taking the first dose. However, its peak effect on potassium conservation and sodium excretion typically occurs between 6 and 10 hours after ingestion. If you are taking it for high blood pressure, it may take several weeks of consistent use before you see the full benefit in your blood pressure readings. Because it has a long duration of action (about 24 hours), it is usually only taken once per day. Your doctor will likely check your blood work within the first week to see how well the drug is working.
You should never stop taking amiloride suddenly without first consulting your healthcare provider. Abruptly discontinuing a diuretic can cause a rapid 'rebound' effect, where your body retains fluid quickly, potentially worsening heart failure or causing a sharp spike in blood pressure. If you are stopping amiloride because your potassium levels are too high, your doctor will provide a specific plan to safely transition you to a different medication. Always follow a medically supervised tapering or switching schedule to avoid putting unnecessary stress on your heart and kidneys.
If you miss a dose of amiloride, take it as soon as you remember that same day. However, if it is almost time for your next scheduled dose, you should skip the missed dose and simply take your next one at the regular time. Never take two doses at once to make up for a missed one, as this significantly increases your risk of developing dangerously high potassium levels (hyperkalemia). Consistency is key for managing blood pressure and electrolytes, so try to use a pillbox or phone alarm to help you remember your daily dose.
Amiloride is a diuretic (water pill), so it is more likely to cause weight loss rather than weight gain, as it helps your body shed excess fluid. If you notice a sudden, rapid increase in weight (such as 3 pounds in a day or 5 pounds in a week) while taking amiloride, this is usually a sign that your condition (like heart failure) is worsening and your body is retaining fluid despite the medication. In such cases, you should contact your doctor immediately. Amiloride does not cause the type of weight gain associated with increased body fat or metabolic changes.
Amiloride has several significant drug interactions that require careful management. It is often safely taken with thiazide or loop diuretics, but it should almost never be taken with potassium supplements, salt substitutes, or other potassium-sparing drugs like spironolactone. It also requires very close monitoring if taken with ACE inhibitors (like lisinopril) or ARBs (like losartan), as these combinations greatly increase the risk of high potassium. Additionally, NSAIDs like ibuprofen can reduce amiloride's effectiveness and harm your kidneys. Always provide your doctor with a complete list of all medications and supplements you use.
Yes, amiloride hydrochloride is widely available as a generic medication in 5 mg tablet form. Generic versions are bioequivalent to the original brand-name drug (Midamor), meaning they have the same active ingredient, strength, and effectiveness. Choosing the generic version is usually much more cost-effective for patients. It is also frequently found in generic combination tablets that include hydrochlorothiazide. Check with your pharmacist to ensure you are receiving the correct generic formulation prescribed by your doctor.