Amiloride Hydrochloride 5 MG Oral Tablet

WARNINGS

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.

DRUG INTERACTIONS

Drug Interactions When amiloride HCl is administered concomitantly with an angiotensin-converting enzyme inhibitor, an angiotensin II receptor antagonist, cyclosporine or tacrolimus, 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.

(See WARNINGS ).

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 amiloride HCl 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 HCl, 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.

OVERDOSAGE

No data are available in regard to overdosage in humans.

The oral LD 50 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.

DESCRIPTION

Amiloride HCl, an antikaliuretic-diuretic agent, is a pyrazine-carbonyl-guanidine that is unrelated chemically to other known antikaliuretic or diuretic agents.

It is the salt of a moderately strong base (pKa 8.7).

It is designated chemically as 3,5-diamino-6-chloro-N-(diaminomethylene) pyrazinecarboxamide monohydrochloride, dihydrate and has a molecular weight of 302.12.

Its empirical formula is C 6 H 8 CIN 7 O•HCl•2H 2 O and its structural formula is: Each tablet for oral administration contains 5 mg of Amiloride HCI, calculated on the anhydrous basis.

Each tablet contains the following inactive ingredients: corn starch, crospovidone, lactose, magnesium stearate, microcrystalline cellulose and povidone.

amiloride structure

HOW SUPPLIED

Each yellow round compressed tablet contains 5 mg of anhydrous Amiloride HCl and is debossed “ Σ ” on one side and “5” on the other.

They are available as follows: NDC 50268-071-15 (10 tablets per card, 5 cards per carton).

Dispensed in Unit Dose Package.

For Institutional Use Only.

Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature].

Manufactured for: AvKARE, Inc.

Pulaski, TN 38478 Mfg.

Rev.

02/09 AV Rev.

09/16 (P) AvPAK

GERIATRIC USE

Geriatric Use Clinical studies of amiloride HCI did not include sufficient numbers of subjects aged 65 and over to determine whether they respond 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.

(See CONTRAINDICATIONS , Impaired Renal Function.

)

INDICATIONS AND USAGE

Amiloride HCl tablets are indicated as adjunctive treatment with thiazide diuretics or other kaliureticdiuretic agents in congestive heart failure or hypertension to: a.

help restore normal serum potassium levels in patients who develop hypokalemia on the kaliuretic diuretic b.

prevent development of hypokalemia in patients who would be exposed to particular risk if hypokalemia were to develop, e.g., digitalized patients or patients with significant cardiac arrhythmias.

The use of potassium-conserving agents is often unnecessary in patients receiving diuretics for uncomplicated essential hypertension when such patients have a normal diet.

Amiloride HCl tablets have little additive diuretic or antihypertensive effect when added to a thiazide diuretic.

Amiloride HCl tablets should rarely be used alone.

It has weak (compared with thiazides) diuretic and antihypertensive effects.

Used as single agents, potassium sparing diuretics, including amiloride HCl tablets, result in an increased risk of hyperkalemia (approximately 10% with amiloride).

Amiloride HCl tablets should be used alone only when persistent hypokalemia has been documented and only with careful titration of the dose and close monitoring of serum electrolytes.

PEDIATRIC USE

Pediatric Use Safety and effectiveness in pediatric patients have not been established.

PREGNANCY

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 in pregnant women.

Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

NUSRING MOTHERS

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 HCl, 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.

BOXED WARNING

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.

DOSAGE AND ADMINISTRATION

Amiloride HCl tablets should be administered with food.

Amiloride HCl tablets, one 5 mg tablet daily, should be added to the usual antihypertensive or diuretic dosage of a kaliuretic diuretic.

The dosage may be increased to 10 mg per day, if necessary.

More than two 5 mg tablets of amiloride HCl daily usually are not needed, and there is little controlled experience with such doses.

If persistent hypokalemia is documented with 10 mg, the dose can be increased to 15 mg, then 20 mg, with careful monitoring of electrolytes.

In treating patients with congestive heart failure after an initial diuresis has been achieved, potassium loss may also decrease and the need for amiloride HCl tablets should be re-evaluated.

Dosage adjustment may be necessary.

Maintenance therapy may be on an intermittent basis.

If it is necessary to use amiloride HCl tablets alone (see INDICATIONS ), the starting dosage should be one 5 mg tablet daily.

This dosage may be increased to 10 mg per day, if necessary.

More than two 5 mg tablets usually are not needed, and there is little controlled experience with such doses.

If persistent hypokalemia is documented with 10 mg, the dose can be increased to 15 mg, then 20 mg, with careful monitoring of electrolytes.