Amiloride and hydrochlorothiazide

Serious side effects have been reported with amiloride and hydrochlorothiazide or its ingredients including the following:

• abnormal heart rhythms (arrhythmia)
• increases in a substance in the blood called urea nitrogen (increases in BUN) and imbalances in the levels of salts and fluids in your body (electrolyte and fluid imbalance). Amiloride and hydrochlorothiazide is especially known to cause elevated potassium levels. Tell your healthcare provider right away if you have some or all of the following symptoms:
  • dry mouth
  • thirst
  • weakness
  • drowsiness
  • restlessness
  • muscle pains or cramps
  • low blood pressure
  • low output of urine
  • fast heart rate
  • nausea
  • vomiting
• acid-base imbalance. Use amiloride and hydrochlorothiazide with caution in patients who are severely ill and at risk for respiratory and metabolic acidosis. 

Amiloride and hydrochlorothiazide can cause dizziness and tiredness (fatigue). Do not drive or operate heavy machinery until you know how this medication affects you.

Do not take amiloride and hydrochlorothiazide if you:

• are allergic to amiloride and hydrochlorothiazide or any of its ingredients or to other sulfonamide-derived drugs
• have high levels of potassium in your blood
• have kidney problems
• you are taking potassium-conserving agents (i.e. spironolactone or triamterene) or potassium supplementation in the form of medication, potassium-containing salt substitutes or a potassium-rich diet. [Except in severe and/or refractory cases of low potassium levels (hypokalemia)]

If you take too much amiloride and hydrochlorothiazide, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away. 

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For amiloride and hydrochlorothiazide, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to amiloride and hydrochlorothiazide or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of amiloride and hydrochlorothiazide combination in the pediatric population. Safety and efficacy have not been established .

Geriatric

Appropriate studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of amiloride and hydrochlorothiazide combination in the elderly. However, elderly patients are more likely to have age-related liver, kidney or heart problems, which may require an adjustment in the dose for patients receiving amiloride and hydrochlorothiazide combination .

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking amiloride and hydrochlorothiazide, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using amiloride and hydrochlorothiazide with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Dofetilide
• Eplerenone
• Triamterene

Using amiloride and hydrochlorothiazide with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aceclofenac
• Acemetacin
• Acetyldigoxin
• Alacepril
• Amphetamine
• Amtolmetin Guacil
• Arginine
• Arsenic Trioxide
• Aspirin
• Benazepril
• Benzphetamine
• Bromfenac
• Bufexamac
• Bupropion
• Captopril
• Celecoxib
• Choline Salicylate
• Cilazapril
• Clonixin
• Cyclophosphamide
• Delapril
• Deslanoside
• Dexibuprofen
• Dexketoprofen
• Dextroamphetamine
• Diclofenac
• Diflunisal
• Digitalis
• Digitoxin
• Digoxin
• Dipyrone
• Dofetilide
• Droperidol
• Droxicam
• Enalaprilat
• Enalapril Maleate
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenoprofen
• Fepradinol
• Feprazone
• Flecainide
• Floctafenine
• Flufenamic Acid
• Flurbiprofen
• Fosinopril
• Ibuprofen
• Imidapril
• Indomethacin
• Ketanserin
• Ketoprofen
• Ketorolac
• Levomethadyl
• Lisdexamfetamine
• Lisinopril
• Lithium
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Meloxicam
• Methamphetamine
• Methotrexate
• Metildigoxin
• Moexipril
• Morniflumate
• Nabumetone
• Naproxen
• Nepafenac
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Ouabain
• Oxaprozin
• Oxyphenbutazone
• Parecoxib
• Pentopril
• Perindopril
• Phenylbutazone
• Piketoprofen
• Piroxicam
• Potassium
• Pranoprofen
• Proglumetacin
• Propyphenazone
• Proquazone
• Proscillaridin
• Quinapril
• Ramipril
• Rofecoxib
• Salicylic Acid
• Salsalate
• Sodium Salicylate
• Sotalol
• Spirapril
• Sulindac
• Temocapril
• Tenoxicam
• Tiaprofenic Acid
• Tolfenamic Acid
• Tolmetin
• Trandolapril
• Trimethoprim
• Valdecoxib
• Zofenopril

Using amiloride and hydrochlorothiazide with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aminolevulinic Acid
• Bepridil
• Carbamazepine
• Carbenoxolone
• Cholestyramine
• Ginkgo
• Gossypol
• Licorice
• Quinidine
• Topiramate

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using amiloride and hydrochlorothiazide with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use amiloride and hydrochlorothiazide, or give you special instructions about the use of food, alcohol, or tobacco.

• Potassium Containing Food

Other Medical Problems

The presence of other medical problems may affect the use of amiloride and hydrochlorothiazide. Make sure you tell your doctor if you have any other medical problems, especially:

• Diabetes or
• Hyperkalemia (high potassium in the blood) or
• Kidney disease (e.g., anuria or diabetic nephropathy)—Should not be used in patients with these conditions .

• Gout or
• Hyperuricemia (high uric acid in the blood) or
• Hypochloremia (low chloride in the blood) or
• Hypokalemia (low potassium in the blood) or
• Hypomagnesemia (low magnesium in the blood) or
• Hyponatremia (low sodium in the blood) or
• Parathyroid disease or
• Systemic lupus erythematosus—Use with caution. amiloride and hydrochlorothiazide may make these conditions worse .

• Heart disease or
• Liver disease, severe (e.g., cirrhosis or hepatic encephalopathy) or
• Lung disease—Use with caution. May increase the chance of side effects .

In addition to the use of amiloride and hydrochlorothiazide, treatment for your high blood pressure may include weight control and changes in the types of foods you eat, especially foods high in sodium. Your doctor will tell you which of these are most important for you. You should check with your doctor before changing your diet .

Many patients who have high blood pressure will not notice any signs of the problem. In fact, many may feel normal. It is very important that you take your medicine exactly as directed and that you keep your appointments with your doctor even if you feel well .

Remember that amiloride and hydrochlorothiazide will not cure your high blood pressure, but it does help control it. You must continue to take it as directed if you expect to lower your blood pressure and keep it down. You may have to take high blood pressure medicine for the rest of your life. If high blood pressure is not treated, it can cause serious problems such as heart failure, blood vessel disease, stroke, or kidney disease .

It is best to take amiloride and hydrochlorothiazide with food .

Dosing

The dose of amiloride and hydrochlorothiazide will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of amiloride and hydrochlorothiazide. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For hypertension or edema:
    • Adults—One tablet once a day. Your doctor may increase your dose if needed.
    • Children—Use and dose must be determined by your doctor .

Missed Dose

If you miss a dose of amiloride and hydrochlorothiazide, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

• It is used to treat high blood pressure.
• It is used to treat heart failure (weak heart).
• It is used to raise potassium stores in the body.
• It may be given to you for other reasons. Talk with the doctor.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Amiloride hydrochloride and hydrochlorothiazide tablets provide diuretic and antihypertensive activity (principally due to the hydrochlorothiazide component), while acting through the amiloride component to prevent the excessive potassium loss that may occur in patients receiving a thiazide diuretic. Due to its amiloride component, the urinary excretion of magnesium is less with Amiloride and Hydrochlorothiazide than with a thiazide or loop diuretic used alone (see PRECAUTIONS). The onset of the diuretic action of this product is within 1 to 2 hours and this action appears to be sustained for approximately 24 hours.

Amiloride Hydrochloride

Amiloride Hydrochloride 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. Amiloride HCl has potassium-conserving activity in patients receiving kaliuretic-diuretic agents.

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

Amiloride HCl 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 HCl usually begins to act within two hours after an oral dose. Its effect on electrolyte excretion reaches a peak between 6 to 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 hydrochloride 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 hydrochloride is excreted in the urine and 40 percent in the stool within 72 hours. Amiloride HCl 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.

Hydrochlorothiazide

The mechanism of the antihypertensive effect of thiazides is unknown. Thiazides do not usually affect normal blood pressure.

Hydrochlorothiazide is a diuretic and antihypertensive. It affects the distal renal tubular mechanism of electrolyte reabsorption. Hydrochlorothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate.

After oral administration diuresis begins within two hours, peaks in about four hours and lasts about 6 to 12 hours.

Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney. When plasma levels have been followed for at least 24 hours, the plasma half-life has been observed to vary between 5.6 and 14.8 hours. At least 61 percent of the oral dose is eliminated unchanged within 24 hours. Hydrochlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.

Hyperkalemia

Amiloride hydrochloride and hydrochlorothiazide tablets 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 hydrochloride and hydrochlorothiazide 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 this product 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 hydrochloride and hydrochlorothiazide. Patients with evidence of renal function 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.

Hypersensitivity

Amiloride hydrochloride and hydrochlorothiazide tablets is contraindicated in patients who are hypersensitive to this product, or to other sulfonamide-derived drugs.

General

Determination of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals.

Patients should be observed for clinical signs of fluid or electrolytes imbalance: i.e., hyponatremia, hypochloremic alkalosis, and hypokalemia. Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids. Warning signs or symptoms of fluid and electrolyte imbalance, irrespective of cause, include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, seizures, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.

Hyponatremia and hypochloremia may occur during the use of thiazides and other diuretics. Any chloride deficit during thiazide therapy is generally mild and may be lessened by the amiloride HCl component of this product. Hypochloremia usually does not require specific treatment except under extraordinary circumstances (as in liver disease or renal disease). Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction, rather than administration of salt, except in rare instances when the hyponatremia is life threatening. In actual salt depletion, appropriate replacement is the therapy of choice.

Hypokalemia may develop during thiazide therapy, especially with brisk diuresis, when severe cirrhosis is present, during concomitant use of corticosteroids or ACTH, or after prolonged therapy. However, this usually is prevented by the amiloride hydrochloride component of this combination drug product.

Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Hypokalemia may cause cardiac arrhythmia and may also sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability).

Thiazides have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia. Amiloride hydrochloride, a component of this combination product, has been shown to decrease the enhanced urinary excretion of magnesium which occurs when a thiazide or loop diuretic is used alone.

Increases in BUN levels have been reported with amiloride hydrochloride and with hydrochlorothiazide. 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 and Hydrochlorothiazide is given to such patients, careful monitoring of serum electrolyte 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 diuretic therapy including amiloride HCl and hydrochlorothiazide.

In patients with renal disease, diuretics may precipitate azotemia. Cumulative effects of the components of amiloride hydrochloride and hydrochlorothiazide may develop in patients with impaired renal function. If renal impairment becomes evident, Amiloride and Hydrochlorothiazide should be discontinued (see CONTRAINDICATIONS and WARNINGS).

Drug Interactions

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 Hydrochlorothiazide plus 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 this product, 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.

When amiloride HCl is administered concomitantly with an angiotensin-converting enzyme inhibitor, 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).

When given concurrently the following drugs may interact with thiazide diuretics.

Potentiation of orthostatic hypotension may occur.

Dosage adjustment of the antidiabetic drug may be required.

Additive effect or potentiation.

Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of cholestyramine and colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85 and 43 percent, respectively.

Intensified electrolyte depletion, particularly hypokalemia.

Possible decreased response to pressor amines but not sufficient to preclude their use.

Possible increased responsiveness to the muscle relaxant.

Generally should not be given with diuretics. Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity. Refer to the package insert for lithium preparations before use of such preparations with this combination product.

Metabolic and Endocrine Effects

In diabetic patients, insulin requirements may be increased, decreased, or unchanged due to the hydrochlorothiazide component. Diabetes mellitus that has been latent may become manifest during administration of thiazide diuretics.

Because calcium excretion is decreased by thiazides, Amiloride and Hydrochlorothiazide should be discontinued before carrying out tests for parathyroid function. Pathologic changes in the parathyroid glands, with hypercalcemia and hypophosphatemia have been observed in a few patients on prolonged thiazide therapy; however, the common complications of hyperparathyroidism such as renal lithiasis, bone resorption, and peptic ulceration have not been seen.

Hyperuricemia may occur or acute gout may be precipitated in certain patients receiving thiazide therapy.

Other Precautions

In patients receiving thiazides, sensitivity reactions may occur with or without a history of allergy or bronchial asthma. The possibility of exacerbation or activation of systemic lupus erythematosus has been reported with the use of thiazides.

Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy.

Carcinogenesis, Mutagenicity, Impairment of Fertility

Long-term studies in animals have not been performed to evaluate the effects upon fertility, mutagenicity or carcinogenic potential of amiloride hydrochloride and hydrochlorothiazide.

There was no evidence of a tumorigenic effect when amiloride hydrochloride was administered for 92 weeks to mice at doses up to 10 mg/kg/day (25 times the maximum daily human dose). Amiloride hydrochloride 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 hydrochloride was devoid of mutagenic activity in various strains of Salmonella typhimurium with or without a mammalian liver microsomal activation system (Ames test).

Two-year feeding studies in mice and rats conducted under the auspices of the National Toxicology Program (NTP) uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in female mice (at doses of up to approximately 600 mg/kg/day) or in male and female rats (at doses up to approximately 100 mg/kg/day). The NTP, however, found equivocal evidence for hepatocarcinogenicity in male mice.

Hydrochlorothiazide was not genotoxic in vitro in the Ames mutagenicity assay of Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations, or in vivo in assays using mouse germinal cell chromosomes, Chinese Hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Positive test results were obtained only in the in vitro CHO Sister Chromatid Exchange (clastogenicity) and in the Mouse Lymphoma Cell (mutagenicity) assays, using concentrations of hydrochlorothiazide from 43 to 1300 mcg/mL, and in the Aspergillus nidulans non-disjunction assay at an unspecified concentration.

Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diet, to doses of up to 100 and 4 mg/kg, respectively, prior to conception and throughout gestation.

Pregnancy

Teratogenic Effects

Teratogenicity studies have been performed with combinations of amiloride hydrochloride and hydrochlorothiazide in rabbits and mice at doses up to 25 times the expected maximum daily dose for humans and have revealed no evidence of harm to the fetus. No evidence of impaired fertility in rats was apparent at dosage levels up to 25 times the expected maximum human daily dose. A perinatal and postnatal study in rats showed a reduction in maternal body weight gain during and after gestation at a daily dose of 25 times the expected maximum daily dose for humans. The body weights of alive pups at birth and at weaning were also reduced at this dose level. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human responses, and because of the data listed below with the individual components, this drug should be used during pregnancy only if clearly needed.

Teratogenicity studies with amiloride hydrochloride 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.

Studies in which hydrochlorothiazide was orally administered to pregnant mice and rats during their respective periods of major organogenesis at doses up to 3000 and 1000 mg hydrochlorothiazide/kg, respectively, provided no evidence of harm to the fetus. There are, however, no adequate and well-controlled studies in pregnant women.

Thiazides cross the placental barrier and appear in cord blood. There is a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.

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 HCl is excreted in human milk. However, thiazides appear in breast milk. Because of the potential for serious adverse reactions in nursing infants, 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 hydrochloride and hydrochlorothiazide tablets 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 the comitant 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).

Amiloride hydrochloride and hydrochlorothiazide tablets should be administered with food.

The usual starting dosage is 1 tablet a day. The dosage may be increased to 2 tablets a day, if necessary. More than 2 tablets of amiloride hydrochloride and hydrochlorothiazide daily usually are not needed and there is no controlled experience with such doses.

Hydrochlorothiazide can be given at doses of 12.5 to 50 mg per day when used alone. Patients usually do not require doses of hydrochlorothiazide in excess of 50 mg daily when combined with other antihypertensive agents. The daily dose is usually given as a single dose but may be given in divided doses. Once an initial diuresis has been achieved, dosage adjustment may be necessary. Maintenance therapy may be on an intermittent basis.

Amiloride Hydrochloride and Hydrochlorothiazide Tablets USP 5 mg/50 mg 100s Label Text

NDC 0555-0483-02

Amiloride

Hydrochloride and

Hydrochlorothiazide

Tablets USP

5 mg/50 mg

Rx only

100 TABLETS

TEVA

(a MIL oh ride & hye droe klor oh THYE a zide)

Store at 20°C to 25°C (68°F to 77°F); protect from light.

Also see individual agents.

1% to 10%:

Cardiovascular: Cardiac arrhythmia (>1%)

Central nervous system: Dizziness (3% to 8%), headache (3% to 8%), fatigue (>1%)

Dermatologic: Skin rash (3% to 8%), pruritus (>1%)

Endocrine & metabolic: Hyperkalemia (1% to 2%), increased serum potassium (>1%; >5.5 mEq/L)

Gastrointestinal: Nausea (3% to 8%), abdominal pain (>1%), diarrhea (>1%), gastrointestinal pain (>1%)

Neuromuscular & skeletal: Leg pain (>1%), weakness (3% to 8%)

Respiratory: Dyspnea (>1%)

<1% (Limited to important or life-threatening): Anorexia, arthralgia, chest pain, confusion, dehydration, depression, digitalis intoxication, erythema multiforme, exfoliative dermatitis, gastrointestinal hemorrhage, gout, hyponatremia (symptomatic), impotence, orthostatic hypertension, renal failure, renal insufficiency, Stevens-Johnson syndrome, syncope, toxic epidermal necrolysis, urinary incontinence, visual disturbance

Initial dose: Amiloride 5 mg-Hydrochlorothiazide 50 mg orally once a day or in divided doses
Maintenance dose: Amiloride 5 to 10 mg-Hydrochlorothiazide 50 to 100 mg orally once a day or in divided doses

Comments:
-Doses greater than amiloride 10 mg-hydrochlorothiazide 100 mg per day are usually not needed and there is no controlled data with such doses.
-Hydrochlorothiazide can be given at doses of 12.5 to 50 mg per day when used alone.
-Patients usually do not require more than hydrochlorothiazide 50 mg per day when combined with other antihypertensive agents.

Use: Treatment of patients with hypertension or congestive heart failure who develop hypokalemia when thiazides or other kaliuretic diuretics are used alone, or in whom maintenance of normal serum potassium levels is considered to be clinically important (e.g., digitalized patients or patients with significant cardiac arrhythmias).

Use is not recommended and a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk: Unknown (amiloride); Yes (hydrochlorothiazide) Excreted into animal milk: Yes (amiloride)