Amiloride Hydrochloride

Name: Amiloride Hydrochloride

Warnings

Hyperkalemia

Like other potassium-conserving agents, amiloride may cause hyperkalemia (serum potassium levels greater than 5.5 mEq per liter) which, if uncorrected, is potentially fatal. Hyperkalemia occurs commonly (about 10%) when amiloride is used without a kaliuretic diuretic. This incidence is greater in patients with renal impairment, diabetes mellitus (with or without recognized renal insufficiency), and in the elderly. When amiloride is used concomitantly with a thiazide diuretic in patients without these complications, the risk of hyperkalemia is reduced to about 1-2%. It is thus essential to monitor serum potassium levels carefully in any patient receiving amiloride, particularly when it is first introduced, at the time of diuretic dosage adjustments, and during any illness that could affect renal function.

The risk of hyperkalemia may be increased when potassium-conserving agents, including amiloride HCl, are administered concomitantly with an angiotensin-converting enzyme inhibitor, an angiotensin II receptor antagonist, cyclosporine or tacrolimus. (See PRECAUTIONS: DRUG INTERACTIONS.) Warning signs or symptoms of hyperkalemia include paresthesias, muscular weakness, fatigue, flaccid paralysis of the extremities, bradycardia, shock, and ECG abnormalities. Monitoring of the serum potassium level is essential because mild hyperkalemia is not usually associated with an abnormal ECG.

When abnormal, the ECG in hyperkalemia is characterized primarily by tall, peaked T waves or elevations from previous tracings. There may also be lowering of the R wave and increased depth of the S wave, widening and even disappearance of the P wave, progressive widening of the QRS complex, prolongation of the PR interval, and ST depression.

Treatment of hyperkalemia: If hyperkalemia occurs in patients taking amiloride HCl, the drug should be discontinued immediately. If the serum potassium level exceeds 6.5 mEq per liter, active measures should be taken to reduce it. Such measures include the intravenous administration of sodium bicarbonate solution or oral or parenteral glucose with a rapid-acting insulin preparation. If needed, a cation exchange resin such as sodium polystyrene sulfonate may be given orally or by enema. Patients with persistent hyperkalemia may require dialysis.

Diabetes Mellitus

In diabetic patients, hyperkalemia has been reported with the use of all potassium-conserving diuretics, including amiloride HCl, even in patients without evidence of diabetic nephropathy. Therefore, amiloride HCl should be avoided, if possible, in diabetic patients and, if it is used, serum electrolytes and renal function must be monitored frequently.

Amiloride HCl should be discontinued at least 3 days before glucose tolerance testing.

Metabolic or Respiratory Acidosis

Antikaliuretic therapy should be instituted only with caution in severely ill patients in whom respiratory or metabolic acidosis may occur, such as patients with cardiopulmonary disease or poorly controlled diabetes. If amiloride HCl is given to these patients, frequent monitoring of acid-base balance is necessary. Shifts in acid-base balance alter the ratio of extracellular/intracellular potassium, and the development of acidosis may be associated with rapid increases in serum potassium levels.

Overdose

No data are available in regard to overdosage in humans.

The oral LD50 of amiloride HCl (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 HCl 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 the serum potassium levels.

Clinical pharmacology

Amiloride HCl is a potassium-conserving (antikaliuretic) drug that possesses weak (compared with thiazide diuretics) natriuretic, diuretic, and antihypertensive activity. These effects have been partially additive to the effects of thiazide diuretics in some clinical studies. When administered with a thiazide or loop diuretic, amiloride has been shown to decrease the enhanced urinary excretion of magnesium which occurs when a thiazide or loop diuretic is used alone. Amiloride has potassium-conserving activity in patients receiving kaliureticdiuretic agents.

Amiloride HCl is not an aldosterone antagonist and its effects are seen even in the absence of aldosterone.

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. This mechanism accounts in large part for the potassium sparing action of amiloride.

Amiloride usually begins to act within 2 hours after an oral dose. Its effect on electrolyte excretion reaches a peak between 6 and 10 hours and lasts about 24 hours. Peak plasma levels are obtained in 3 to 4 hours and the plasma half-life varies from 6 to 9 hours. Effects on electrolytes increase with single doses of amiloride HCl up to approximately 15 mg.

Amiloride HCl is not metabolized by the liver but is excreted unchanged by the kidneys. About 50 percent of a 20 mg dose of amiloride HCl is excreted in the urine and 40 percent in the stool within 72 hours. Amiloride has little effect on glomerular filtration rate or renal blood flow. Because amiloride HCl is not metabolized by the liver, drug accumulation is not anticipated in patients with hepatic dysfunction, but accumulation can occur if the hepatorenal syndrome develops.

Uses for Amiloride Hydrochloride

Amiloride should rarely be used alone, because such use may result in increased risk of hyperkalemia.a b Use alone only when persistent hypokalemia has been documented.b

Hypokalemia Induced by Kaliuretic Diuretics

Treatment or prevention of hypokalemia induced by thiazide or other kaliuretic diuretics in patients with heart failure or hypertension.a b c

May be particularly useful for preventing diuretic-induced hypokalemia in patients in whom the clinical consequences of hypokalemia represent an important risk, such as patients receiving cardiac glycosides or those with cardiac arrhythmias.a b c

Also useful in patients with hypokalemia who do not respond to potassium supplements or those who cannot tolerate potassium supplements.a

Potassium-sparing effect of amiloride generally persists during prolonged therapy with the drug, but may diminish with time in some patients.a

Potassium-sparing effect of amiloride is additive with that of spironolactone.a May be effective in some patients unresponsive to spironolactone; unlike spironolactone, diuretic effect of amiloride is independent of aldosterone concentrations.a

Edema

Management of edema associated with heart failure, cirrhosis of the liver, or secondary hyperaldosteronism.a

Generally, use in combination with other more effective, rapidly acting diuretics, such as thiazides, chlorthalidone, or loop diuretics (e.g., furosemide), to decrease potassium excretion caused by kaliuretic diuretics.a b

Used in fixed combination with hydrochlorothiazide for treatment of edema in patients who require a thiazide diuretic and in whom the development of hypokalemia cannot be risked.c

Heart Failure

Management of edema associated with heart failure, generally used in conjunction with other more effective, rapidly acting diuretics (e.g., thiazides, chlorthalidone, loop diuretics).a

Most experts state that loop diuretics (e.g., bumetanide, ethacrynic acid, furosemide, torsemide) are the diuretics of choice for most patients with heart failure.524

Most experts state that all patients with symptomatic heart failure who have evidence for, or a history of, fluid retention generally should receive diuretic therapy in conjunction with moderate sodium restriction, an agent to inhibit the renin-angiotensin-aldosterone (RAA) system (e.g., ACE inhibitor, angiotensin II receptor antagonist, angiotensin receptor-neprilysin inhibitor [ARNI]), a β-adrenergic blocking agent (β-blocker), and in selected patients, an aldosterone antagonist.524 700 713

Hypertension

Management of hypertension;500 502 504 however, other agents (i.e., ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, thiazide diuretics) are preferred for initial management.501 502 503 504

Amiloride alone has mild hypotensive activity.a b

Used concomitantly with a thiazide diuretic mainly to prevent or treat diuretic-induced hypokalemia.a b (See Hypokalemia Induced by Kaliuretic Diuretics under Uses.) The manufacturers state that amiloride produces little additive hypotensive activity when used concurrently with a thiazide diuretic.a b

Some experts state that inclusion in combination drug regimens may be considered in patients with resistant hypertension.502

Used in fixed combination with hydrochlorothiazide for treatment of hypertension in patients who require a thiazide diuretic and in whom the development of hypokalemia cannot be risked and in patients who develop hypokalemia during hydrochlorothiazide monotherapy.c

Use the amiloride/hydrochlorothiazide fixed combination alone or as an adjunct to other antihypertensive agents (e.g., methyldopa, β-blocker).c

Hyperaldosteronism

Has been used to control hypertension and correct electrolyte abnormalities associated with primary hyperaldosteronism†.a

Also has been used for the management of secondary hyperaldosteronism† (Bartter’s syndrome) to correct hypokalemia.a

Diuretic-induced Metabolic Alkalosis

Has been used to correct the metabolic alkalosis† produced by thiazides and other kaliuretic diuretics.a

Calcium Nephrolithiasis

Has been used in combination with hydrochlorothiazide in patients with recurrent calcium nephrolithiasis†.a

Lithium-induced Polyuria

Has been used for the management of lithium-induced polyuria† (secondary to lithium-induced nephrogenic diabetes insipidus).100 a (See Specific Drugs, Foods, and Laboratory Tests under Interactions.)

Stability

Storage

Oral

Tablets

<40°C (preferably 15–30°C);a protect from moisture, freezing, and excessive heat.a b

Fixed Combination Tablets with Hydrochlorothiazide

15–30°C; protect from light, moisture, and freezing.c

  • Diuretics
  • High Blood Pressure (Hypertension) Medications

© Amiloride hydrochloride Patient Information is supplied by Cerner Multum, Inc. and Amiloride hydrochloride Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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