NDC 42794-005 Amiloride Hydrochloride

Amiloride Hydrochloride

NDC Product Code 42794-005

NDC CODE: 42794-005

Proprietary Name: Amiloride Hydrochloride What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Amiloride Hydrochloride What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Product Characteristics

Color(s):
YELLOW (C48330)
Shape: ROUND (C48348)
Size(s):
8 MM
Imprint(s):
5
Score: 1

NDC Code Structure

  • 42794 - Sigmapharm Laboratories, Llc

NDC 42794-005-02

Package Description: 100 TABLET in 1 BOTTLE

NDC Product Information

Amiloride Hydrochloride with NDC 42794-005 is a a human prescription drug product labeled by Sigmapharm Laboratories, Llc. The generic name of Amiloride Hydrochloride is amiloride hydrochloride. The product's dosage form is tablet and is administered via oral form. The RxNorm Crosswalk for this NDC code indicates a single RxCUI concept is associated to this product: 977880.

Dosage Form: Tablet - A solid dosage form containing medicinal substances with or without suitable diluents.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Amiloride Hydrochloride Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.


Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • STARCH, CORN (UNII: O8232NY3SJ)
  • CROSPOVIDONE (UNII: 2S7830E561)
  • LACTOSE (UNII: J2B2A4N98G)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)
  • POVIDONE (UNII: FZ989GH94E)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Decreased Renal K+ Excretion - [PE] (Physiologic Effect)
  • Increased Diuresis - [PE] (Physiologic Effect)
  • Potassium-sparing Diuretic - [EPC] (Established Pharmacologic Class)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Sigmapharm Laboratories, Llc
Labeler Code: 42794
FDA Application Number: ANDA079133 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 06-14-2021 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2022 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

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Amiloride Hydrochloride Product Label Images

Amiloride Hydrochloride Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

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


6H


8CIN


7O•HCl•2H


2O 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.

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.

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.

Contraindications

Hyperkalemia Amiloride HCl tablets should not be used in the presence of elevated serum
potassium levels (greater than 5.5 mEq per liter).Antikaliuretic Therapy or Potassium
SupplementationAmiloride HCl tablets 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 HCl tablets 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 FunctionAnuria, acute or chronic renal insufficiency, and evidence of diabetic
nephropathy are contraindications to the use of amiloride HCl tablets. 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.HypersensitivityAmiloride HCl tablets are contraindicated in patients who are hypersensitive
to this product.WARNINGS

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.

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 MellitusIn 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 AcidosisAntikaliuretic 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.

General Precautions

Electrolyte Imbalance and BUN Increases
Hyponatremia and hypochloremia may occur when amiloride HCl is used with
other diuretics and increases in BUN levels have been reported. These increases
usually have accompanied vigorous fluid elimination, especially when diuretic
therapy was used in seriously ill patients, such as those who had hepatic
cirrhosis with ascites and metabolic alkalosis, or those with resistant edema.
Therefore, when amiloride HCl is given with other diuretics to such patients,
careful monitoring of serum electrolytes and BUN levels is important. In
patients with pre-existing severe liver disease, hepatic encephalopathy,
manifested by tremors, confusion, and coma, and increased jaundice, have been
reported in association with diuretics, including amiloride HCl.

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.

Carcinogenesis And Mutagenesis And Impairment Of Fertility

There was no evidence of a tumorigenic effect when amiloride HCl
was administered for 92 weeks to mice at doses up to 10 mg/kg/day (25 times the
maximum daily human dose). Amiloride HCl has also been administered for 104
weeks to male and female rats at doses up to 6 and 8 mg/kg/day (15 and 20 times
the maximum daily dose for humans, respectively) and showed no evidence of
carcinogenicity.Amiloride HCl was devoid of mutagenic activity in various strains of
Salmonella typhimurium with or without a mammalian liver microsomal activation
system (Ames test).

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.

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.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

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.)

Adverse Reactions

Amiloride HCl is usually well tolerated and, except for hyperkalemia (serum potassium levels greater than 5.5 mEq liter - see


WARNINGS), significant adverse effects have been reported infrequently. Minor adverse reactions were reported relatively frequently (about 20%) but the relationship of many of the reports to amiloride HCl is uncertain and the overall frequency was similar in hydrochlorothiazide treated groups. Nausea/anorexia, abdominal pain, flatulence, and mild skin rash have been reported and probably are related to amiloride. Other adverse experiences that have been reported with amiloride are generally those known to be associated with diuresis, or with the underlying disease being treated.


The adverse reactions for amiloride HCl listed in the following table have been arranged into two groups: (1) incidence greater than one percent; and (2) incidence one percent or less. The incidence for group (1) was determined from clinical studies conducted in the United States (837 patients treated with amiloride HCl). The adverse effects listed in group (2) include reports from the same clinical studies and voluntary reports since marketing. The probability of a causal relationship exists between amiloride HCl and these adverse reactions, some of which have been reported only rarely.Incidence > 1%Incidence ≤ 1%Body as a WholeHeadache*Back painWeaknessChest painFatigabilityNeck/shoulder achePain, extremitiesCardiovascularNoneAngina pectorisOrthostatic hypotension


Arrhythmia


Palpitation


DigestiveNausea/anorexia*JaundiceDiarrhea*GI bleedingVomiting*Abdominal fullnessAbdominal painGI disturbanceGas painThirstAppetite changesHeartburnConstipationFlatulenceDyspepsiaMetabolic Elevated serum potassium levels


(>5.5 mEq per liter)**


  NoneSkinNoneSkin rashItching


Dryness of mouth


Pruritus


Alopecia


MusculoskeletalMuscle crampsJoint painLeg acheNervousDizzinessParesthesiaEncephalopathyTremorsVertigoPsychiatricNoneNervousnessMental confusion


Insomnia


Decreased libido


Depression


Somnolence


RespiratoryCoughShortness of BreathDyspneaSpecial SensesNoneVisual disturbancesNasal congestion


Tinnitus


Increased intraocular pressure


UrogenitalImpotencePolyuriaDysuria


Urinary frequency


Bladder spasms


Gynecomastia


*Reactions occurring in 3% to 8% of patients treated with amiloride HCl.  (Those reactions occurring in less than 3% of the patients are unmarked.) **See


WARNINGSCausal Relationship Unknown Other reactions have been reported but occurred under circumstances where a causal relationship could not be established. However, in these rarely reported events, that possibility cannot be excluded. Therefore, these observations are listed to serve as alerting information to physicians.Activation of probable pre-existing peptic ulcerAplastic anemiaNeutropeniaAbnormal liver functionTo report 


SUSPECTED ADVERSE REACTIONS, contact Sigmapharm Laboratories, LLC, Pharmacovigilance at 1-855-332-0731 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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.

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.

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 in bottles of 100’s (NDC #42794-005-02).Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature].Dispense in a tight, light-resistant container as defined in the USP.Sigmapharm Laboratories, LLCBensalem, PA 19020OS005A-01 REV.0321

Package Label Principal Display

Sigmapharm Laboratories, LLCNDC 42794-005-02


Amiloride Hydrochloride Tablets USP5 mg


Rx Only100 Tablets

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