Brands, Medical Use, Clinical Data
Brands / Synonyms
Amilorida [INN-Spanish]; Amiloride HCL; Amiloride hydrochloride; Amiloride hydrochloride hydrate
; Amiloridum [INN-Latin]; Amipramidin; Amipramizid; Amipramizide; Amiprazidine; AMR; Guanamprazin; Guanamprazine; Midamor; Moduretic
For use as adjunctive treatment with thiazide diuretics or other kaliuretic-diuretic agents in congestive heart failure or hypertension.
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 concurrent use of ACE inhibitors or spironolactone. Patients are also advised not to use potassium-containing salt replacements.
Mechanism of Action
Amiloride works by inhibiting sodium reabsorption in the distal convoluted tubules and collecting ducts in the kidneys by binding to the amiloride-sensitive sodium channels. This promotes the loss of sodium and water from the body, but without depleting potassium. Amiloride exerts its potassium sparing effect through the inhibition of sodium reabsorption at the distal convoluted tubule, cortical collecting tubule and collecting duct; this decreases the net negative potential of the tubular lumen and reduces both potassium and hydrogen secretion and their subsequent excretion. Amiloride is not an aldosterone antagonist and its effects are seen even in the absence of aldosterone.
Readily absorbed following oral administration.
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. The most likely signs and symptoms to be expected with overdosage are dehydration and electrolyte imbalance.
Biotrnasformation / Drug Metabolism
Amiloride is not metabolized by the liver but is excreted unchanged by the kidneys.
MIDAMOR should not be used in the presence of elevated serum potassium levels (greater than 5.5 mEq per
Antikaliuretic Therapy or Potassium Supplementation
MIDAMOR 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 MIDAMOR 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 MIDAMOR. 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 antikaliuretic agent is accentuated in the presence of renal impairment and
may result in the rapid development of hyperkalemia.
MIDAMOR is contraindicated in patients who are hypersensitive to this product.
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 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.
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 MIDAMOR
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 MIDAMOR, 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.