Amiloride

Amiloride is an antihypertensive agent belonging to Potassium Sparing Diuretics.

Amiloride is a potassium-sparing diuretic that is used to control high blood pressure and edema. Amiloride is also used in the treatment of congestive heart failure and liver cirrhosis with ascites.

Readily absorbed following oral administration. The bioavailability of Amiloride is about 30-90%. Amiloride usually begins to act within 2 hours. Time to peak plasma concentration and Duration of action of Amiloride was found to be approximately 3-4 hours and 24 hours respectively. The mean apparent volume of distribution ranges from 350 L to 380 L. Amiloride bound to plasma proteins is approximately 23%. Amiloride is not metabolized by the liver but is excreted unchanged by the kidneys. Plasma half-life varies from 6 to 9 hours. Amiloride is excreted in the urine about 50% and 40-50% from feces within 72 hours.

Amiloride shows common side effects Abdominal pain, confusion, difficulty with breathing, irregular heartbeat, nausea or vomiting, nervousness, numbness or tingling in the hands, feet, or lips, shortness of breath, weakness or heaviness of the legs, etc.

Amiloride is available in the form of Oral Tablets.

Amiloride is available in India, the US, the UK, Japan, Austria, Canada, China, and Italy.

Amiloride belonging to the Potassium Sparing Diuretics acts as an antihypertensive agent.

Amiloride 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.

The onset of action of Amiloride occurs within 2 hours.

The Duration of Action for Amiloride in the body is approximately 24 hours and Tmax was found within 3-4 hours.

• Amiloride is available in the form of Oral Tablets.

• Amiloride Tablets are taken orally, and it is usually taken once a day.

Amiloride is a potassium-sparing diuretic which is used to control high blood pressure and edema. Amiloride also used in the treatment of congestive heart failure and liver cirrhosis with ascites. This medicine is not recommended for use in the patients with hyperkalemia (elevated levels of potassium in the blood).

Amiloride is an antihypertensive agent belonging to Potassium Sparing Diuretics.

Amiloride is a weak diuretic that acts mainly on the distal renal tubules. It increases the excretion of Na and decreases the excretion of potassium. It diminishes the kaliuretic effects of other diuretics and may produce an additional natriuretic effect.

Amiloride is approved for use in the following clinical indications

• Amiloride is used in treatment of Hypertension.
• Amiloride is used in treatment of edema.
• Amiloride is used in treatment of Congestive heart failure.
• Amiloride also used in the treatment of liver cirrhosis with ascites. (off-label)

• Hypertension

Initial dose: 5 mg orally once a day.

Maintenance dose: 5-10 mg once a day.

• Edema

Initial dose: 5 mg orally once a day.

Maintenance dose: 5-10 mg once a day.

• Congestive Heart Failure

Initial dose: 5 mg orally once a day.

Maintenance dose: 5-10 mg once a day.

Although not approved, there have been certain off-label indications. These include

• Liver Cirrhosis Ascites

Initial dose: 5 mg orally once a day.

Maintenance dose: 5-10 mg once a day.

Amiloride is available in the form of an Oral Tablet.

Do not use potassium-containing salt substitutes such as Bananas, oranges, potatoes, peas, mushrooms, cantaloupe, honeydew, apricots, grapefruit, raisins, and dates.

Amiloride is contraindicated in patients with

• Hyperkalemia

Amiloride should not be used in the presence of elevated serum potassium levels (greater than 5.5 mEq per liter).

• Antikaliuretic Therapy or Potassium Supplementation

Amiloride should not be given to patients receiving other potassium-conserving agents, such as spironolactone or triamterene. Potassium supplementation in the form of medication, potassium-containing salt substitutes, or a potassium-rich diet should not be used with Amiloride except in severe and/or refractory cases of hypokalemia. Such concomitant therapy can be associated with rapid increases in serum potassium levels. If potassium supplementation is used, careful monitoring of the serum potassium level is necessary.

• Impaired Renal Function

Anuria, acute or chronic renal insufficiency, and evidence of diabetic nephropathy are contraindications to the use of Amiloride. Patients with evidence of renal functional impairment (blood urea nitrogen [BUN] levels over 30 mg per 100 mL or serum creatinine levels over 1.5 mg per 100 mL) or diabetes mellitus should not receive the drug without careful, frequent, and continuing monitoring of serum electrolytes, creatinine, and BUN levels. Potassium retention associated with the use of an antidiuretic agent is accentuated in the presence of renal impairment and may result in the rapid development of hyperkalemia.

• Hypersensitivity

Amiloride is contraindicated in patients who are hypersensitive to this product.

• 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 the 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.

The 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.

• Adrenal insufficiency

Avoid the use of diuretics for the treatment of elevated blood pressure in patients with primary adrenal insufficiency (Addison disease). Adjustment of glucocorticoid/mineralocorticoid therapy and/or the use of other antihypertensive agents is preferred to treat hypertension.

• 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 it 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.

Consumption of alcohol is not recommended while receiving Amiloride as it may increase the risk of hypotension and adverse effects such as dizziness, fainting, lightheadedness, etc.

Studies in rats have shown that Amiloride is excreted in milk in concentrations higher than those found in blood, but it is not known whether Amiloride is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Amiloride, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pregnancy category B.

Animal studies have revealed no evidence of teratogenicity or impaired fertility, although a decrease in rat pup growth and survival was observed at doses 5 or more times the expected maximum daily dose for humans. There are no controlled data on human pregnancy. Amiloride should only be given during pregnancy when the need has been clearly established.

Do not use potassium-containing salt substitutes such as Bananas, oranges, potatoes, peas, mushrooms, cantaloupe, honeydew, apricots, grapefruit, raisins, and dates.

• Common Adverse effects

Dizziness, fatigue, headache, hyperkalaemia, dehydration, gynecomastia, hyperchloremic metabolic acidosis, hyponatremia, Abdominal pain, change in appetite, constipation, diarrhoea, gas pain, nausea, vomiting, impotence, muscle cramps, weakness, cough, dyspnea.

• Rare Adverse effects

Alopecia, bladder spasm, cardiac arrhythmia, chest pain, dysuria, gastrointestinal hemorrhage, increased intraocular pressure, jaundice, orthostatic hypotension, palpitations, polyuria

• Angiotensin-converting enzyme inhibitor

When amiloride HCl is administered concomitantly with an angiotensin-converting enzyme inhibitor, the risk of hyperkalemia may be increased. Therefore, if concomitant use of these agents is indicated because of demonstrated hypokalemia, they should be used with caution and with frequent monitoring of serum potassium.

• Lithium

Lithium generally should not be given with diuretics because they reduce its renal clearance and add a high risk of lithium toxicity. Read circulars for lithium preparations before use of such concomitant therapy.

• Non-steroidal anti-inflammatory agent

In some patients, the administration of a non-steroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing, and thiazide diuretics. Therefore, when Amiloride and non-steroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained. Since indomethacin and potassium-sparing diuretics, including Amiloride, may each be associated with increased serum potassium levels, the potential effects on potassium kinetics and renal function should be considered when these agents are administered concurrently.

The common side effects of Amiloride include the following

• Common

Abdominal pain, confusion, difficulty with breathing, irregular heartbeat, nausea or vomiting, nervousness, numbness or tingling in the hands, feet, or lips, shortness of breath, weakness or heaviness of the legs.

• Less Common

Agitation, back pain, blurred vision, coma, dizziness, Drowsiness, fever, hallucinations (seeing things that aren't there), headache, irritability, labored breathing, mood or mental changes, seizures (convulsions), stiff neck, tightness in the chest, unusual tiredness or weakness, vomiting, wheezing

• Rare

Arm or jaw pain, bloody or black, tarry stools, burning while urinating, crawling, itching, numbness, prickling, pins, and needles or tingling feelings, change in vision, chest pain, discomfort or heaviness, Chills, clay-colored stools, constipation, dark urine, difficult or painful urination, dizziness, faintness or lightheadedness when getting up from a lying or sitting position suddenly, racing or slow heartbeat or pulse, itching, light-colored stools, loss of appetite, loss of vision, rash, shakiness in the legs, arms, hands, or feet, stomach pain, sweating, trembling or shaking of the hands or feet, unpleasant breath odor, vomiting of blood or material that looks like coffee grounds and yellow eyes or skin.

• Pregnancy

Pregnancy Category B: Teratogenicity studies with amiloride HCl in rabbits and mice given 20 and 25 times the maximum human dose, respectively, revealed no evidence of harm to the fetus, although studies showed that the drug crossed the placenta in modest amounts. Reproduction studies in rats at 20 times the expected maximum daily dose for humans showed no evidence of impaired fertility. At approximately 5 or more times the expected maximum daily dose for humans, some toxicity was seen in adult rats and rabbits and a decrease in rat pup growth and survival occurred.

There are, however, no adequate and well-controlled studies on pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

• Nursing Mothers

Studies in rats have shown that amiloride is excreted in milk in concentrations higher than those found in blood, but it is not known whether Amiloride is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Amiloride, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

• Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

• Geriatric Use

Clinical studies of Amiloride did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

• No data are available in regard to overdosage in humans. The oral LD₅₀ of amiloride hydrochloride (calculated as the base) is 56 mg/kg in mice and 36 to 85 mg/kg in rats, depending on the strain.
• It is not known whether the drug is dialyzable.
• The most likely signs and symptoms to be expected with overdosage are dehydration and electrolyte imbalance. These can be treated by established procedures. Therapy with Amiloride should be discontinued and the patient observed closely. There is no specific antidote. Emesis should be induced or gastric lavage performed. Treatment is symptomatic and supportive. If hyperkalemia occurs, active measures should be taken to reduce serum potassium levels.

Pharmacodynamic

Amiloride, an antikaliuretic-diuretic agent, is a pyrazine-carbonyl-guanidine that is unrelated chemically to other known antikaliuretic or diuretic agents. It is an antihypertensive, potassium-sparing diuretic that was first approved for use in 1967 and helps to treat hypertension and congestive heart failure. The drug is often used in conjunction with thiazide or loop diuretics. Due to its potassium-sparing capacities, hyperkalemia (high blood potassium levels) are occasionally observed in patients taking amiloride. The risk is high in the concurrent use of ACE inhibitors or spironolactone. Patients are also advised not to use potassium-containing salt replacements.

Pharmacokinetics

• Absorption

Readily absorbed following oral administration. The bioavailability of Amiloride is about 30-90%. Amiloride usually begins to act within 2 hours. Time to peak plasma concentration and Duration of action of Amiloride was found to be approximately 3-4 hours and 24 hours respectively.

• Distribution

Amiloride is widely distributed in the tissues. The mean apparent volume of distribution ranges from 350 L to 380 L. Amiloride bound to plasma proteins is approximately 23%.

• Metabolism and Excretion

Amiloride is not metabolized by the liver but is excreted unchanged by the kidneys. Plasma half-life varies from 6 to 9 hours. Amiloride is excreted in the urine about 50% and 40-50% from feces within 72 hours.

• https://www.rxlist.com/midamor-drug.htm#indications
• https://www.uptodate.com/contents/amiloride-drug-information#F133006
• https://www.mims.com/india/drug/info/amiloride?type=full&mtype=generic#mechanism-of-action
• https://reference.medscape.com/drug/midamor-amiloride-342406
• https://www.drugs.com/dosage/amiloride.html
•  https://www.practo.com/medicine-info/amiloride-766-api