MODURETIC (Amiloride HCl-Hydrochlorothiazide) combines the potassium-conserving action of amiloride HCl with the natriuretic action of hydrochlorothiazide.

Amiloride HCl 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 C₆H₈C_lN₇OH₀₂H₂O and its structural formula is:

Hydrochlorothiazide is designated chemically as 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is C₇H₈C_lN₃O₄S₂ and its structural formula is:

It is a white, or practically white, crystalline powder with a molecular weight of 297.74, which is slightly soluble in water, but freely soluble in sodium hydroxide solution.

MODURETIC is available for oral use as tablets containing 5 mg of anhydrous amiloride HCl and 50 mg of hydrochlorothiazide. Each tablet contains the following inactive ingredients: calcium phosphate, FD&C Yellow 6, guar gum, lactose, magnesium stearate and starch.

Last updated on RxList: 4/24/2009

MODURETIC is indicated in those patients with hypertension or with 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.

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

MODURETIC may be used alone or as an adjunct to other antihypertensive drugs, such as methyldopa or beta blockers. Since MODURETIC enhances the action of these agents, dosage adjustments may be necessary to avoid an excessive fall in blood pressure and other unwanted side effects.

This fixed combination drug is not indicated for the initial therapy of edema or hypertension except in individuals in whom the development of hypokalemia cannot be risked.

MODURETIC 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 MODURETIC 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.

No. 3385 — Tablets MODURETIC are peach-colored, diamond-shaped, scored, compressed tablets, coded MSD 917 on one side and M on the other. Each tablet contains 5 mg of anhydrous amiloride HCl and 50 mg of hydrochlorothiazide. They are supplied as follows:

NDC 0006-0917-68 in bottles of 100.

Storage

Keep container tightly closed. Protect from light, moisture, freezing, -20°C (-4°F) and store at room temperature, 15-30°C (59-86°F).

MERCK & CO., INC., Whitehouse Station, NJ 08889, USA. Issued November 2002

Last updated on RxList: 4/24/2009

MODURETIC is usually well tolerated and significant clinical adverse effects have been reported infrequently. The risk of hyperkalemia (serum potassium levels greater than 5.5 mEq per liter) with MODURETIC is about 1-2 percent in patients without renal impairment or diabetes mellitus (see WARNINGS). Minor adverse reactions to amiloride HCl have been 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 MODURETIC are generally those known to be associated with diuresis, thiazide therapy, or with the underlying disease being treated. Clinical trials have not demonstrated that combining amiloride and hydrochlorothiazide increases the risk of adverse reactions over those seen with the individual components.

The adverse reactions for MODURETIC 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 (607 patients treated with MODURETIC). 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 MODURETIC and these adverse reactions, some of which have been reported only rarely.

Incidence > 1%	Incidence ≤ 1%
Body as a Whole    Headache**    Weakness**    Fatigue/tiredness	Malaise Chest pain Back pain Syncope
Cardiovascular Arrhythmia	Tachycardia Digitalis toxicity Orthostatic hypotension Angina pectoris
Digestive    Nausea/anorexia**    Diarrhea    Gastrointestinal pain    Abdominal pain	Constipation GI bleeding GI disturbance Appetite changes Abdominal fullness Hiccups Thirst Vomiting Anorexia Flatulence
Metabolic    Elevated serum potassium levels ( > 5.5 mEq per liter)***	Gout Dehydration Symptomatic hyponatremiat
Musculoskeletal    Leg ache	Muscle cramps/spasm Joint pain
Nervous    Dizziness**	Paresthesia/numbness Stupor Vertigo
Psychiatric    None	Insomnia Nervousness Depression Sleepiness Mental confusion
Respiratory    Dyspnea	None
Skin    Rash**    Pruritus	Flushing Diaphoresis Erythema multiforme including Stevens-Johnson syndrome Exfoliative dermatitis including toxic epidermal necrolysis Alopecia
Special Senses    None	Bad taste Visual disturbance Nasal congestion
Urogenital    None	Impotence Nocturia Dysuria Incontinence Renal dysfunction including renal failure Gynecomastia
** Reactions occurring in 3% to 8% of patients treated with MODURETIC. (Those reactions occurring in less than 3% of the patients are unmarked.) ***See WARNINGS. †See PRECAUTIONS.

Other adverse reactions that have been reported with the individual components and within each category are listed in order of decreasing severity:

Amiloride

Body as a Whole: Painful extremities, neck/shoulder ache, fatigability; Cardiovascular: Palpitation; Digestive: Activation of probable pre-existing peptic ulcer, abnormal liver function, jaundice, dyspepsia, heartburn; Hematologic: Aplastic anemia, neutropenia; Integumentary: Alopecia, itching, dry mouth; Nervous System/Psychiatric: Encephalopathy, tremors, decreased libido; Respiratory: Shortness of breath, cough; Special Senses: Increased intraocular pressure, tinnitus; Urogenital: Bladder spasms, polyuria, urinary frequency.

Hydrochlorothiazide

Digestive: Pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, gastric irritation; Hematologic: Aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia; Hypersensitivity: Anaphylactic reactions, necrotizing angiitis (vasculitis, cutaneous vasculitis), respiratory distress including pneumonitis and pulmonary edema, photosensitivity, fever, urticaria, purpura; Metabolic: Electrolyte imbalance (see PRECAUTIONS), hyperglycemia, glycosuria, hyperuricemia; Nervous System/Psychiatric: Restlessness; Special Senses: Transient blurred vision, xanthopsia; Urogenital: Interstitial nephritis (see WARNINGS).

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 MODURETIC 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 MODURETIC, 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.

Amiloride HCl

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.)

Hydrochlorothiazide

When given concurrently the following drugs may interact with thiazide diuretics. Alcohol, barbiturates, or narcotics — potentiation of orthostatic hypotension may occur. Antidiabetic drugs (oral agents and insulin) — dosage adjustment of the antidiabetic drug may be required.

Other antihypertensive drugs — additive effect or potentiation.

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

Corticosteroids, ACTH — intensified electrolyte depletion, particularly hypokalemia.

Pressor amines (e.g., norepinephrine) — possible decreased response to pressor amines but not sufficient to preclude their use.

Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine) — possible increased responsiveness to the muscle relaxant.

Lithium — 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 MODURETIC.

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, MODURETIC 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.

Last updated on RxList: 4/24/2009

Hyperkalemia

The risk of hyperkalemia may be increased when potassium-conserving agents, including MODURETIC, 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 MODURETIC, 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, MODURETIC should be avoided, if possible, in diabetic patients and, if it is used, serum electrolytes and renal function must be monitored frequently.

MODURETIC should be discontinued at least three 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 MODURETIC 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

Electrolyte Imbalance and BUN Increases

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 electrolyte 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 MODURETIC. 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 HCl component of MODURETIC.

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 HCl, a component of MODURETIC, 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 HCl 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 MODURETIC 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 MODURETIC may develop in patients with impaired renal function. If renal impairment becomes evident, MODURETIC should be discontinued (see CONTRAINDICATIONS and WARNINGS).

Carcinogenicity, Mutagenicity, Impairment of Fertility

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

Amiloride HCl

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).

Hydrochlorothiazide

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 of 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 ug/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

Pregnancy Category B

Teratogenicity studies have been performed with combinations of amiloride HCl 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.

Amiloride HCl

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.

Hydrochlorothiazide

Teratogenic Effects: 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.

Nonteratogenic Effects: 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 MODURETIC 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.)

Last updated on RxList: 4/24/2009

No data are available in regard to overdosage in humans. The oral LD₅₀ of the combination drug is 189 and 422 mg/kg for female mice and female rats, respectively. It is not known whether the drug is dialyzable.

No specific information is available on the treatment of overdosage with MODURETIC, and no specific antidote is available. Treatment is symptomatic and supportive. Therapy with MODURETIC should be discontinued and the patient observed closely. Suggested measures include induction of emesis and/or gastric lavage.

Amiloride HCl: 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.

The most common signs and symptoms to be expected with overdosage are dehydration and electrolyte imbalance. If hyperkalemia occurs, active measures should be taken to reduce the serum potassium levels.

Hydrochlorothiazide: The oral LD₅₀ of hydrochlorothiazide is greater than 10.0 g/kg in both mice and rats.

The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias.

Hyperkalemia

MODURETIC should not be used in the presence of elevated serum potassium levels (greater than 5.5 mEq per liter).

Antikaliuretic Therapy or Potassium Supplementation

MODURETIC 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 MODURETIC 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 MODURETIC. 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.

Hypersensitivity

MODURETIC is contraindicated in patients who are hypersensitive to this product, or to other sulfonamide-derived drugs.

Last updated on RxList: 4/24/2009

MODURETIC provides 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 MODURETIC than with a thiazide or loop diuretic used alone (see PRECAUTIONS). The onset of the diuretic action of MODURETIC is within 1 to 2 hours and this action appears to be sustained for approximately 24 hours.

Amiloride HCl

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. 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 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 to9 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 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 use 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.

Last updated on RxList: 4/24/2009

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Last updated on RxList: 4/24/2009

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

AMILORIDE/HYDROCHLOROTHIAZIDE - ORAL

(a-MIL-oh-ride/HYE-droe-KLOR-oh-THYE-a-zide)

COMMON BRAND NAME(S): Moduretic

WARNING: Amiloride may infrequently cause high blood potassium levels (hyperkalemia). If left untreated, hyperkalemia may rarely be fatal. Hyperkalemia is more likely to occur when amiloride is used alone, in the elderly, or in people with kidney problems or diabetes. It is very important to have your blood potassium levels checked from time to time while taking this medication, especially at first. If your doctor changes your dose of any of the other medications that may be used with amiloride, or if you develop new medical problems that affect your kidneys, you may need to have your blood potassium level checked more frequently. Keep all medical and laboratory appointments. Seek immediate medical attention if you notice any of the following unlikely but serious side effects: muscle weakness, slow heartbeat, tingling of the hands/feet, unusual tiredness.

This product contains two medications and generally, this product should not be used when treating your condition for the first time. Each of the two different drugs in this product should first be given separately so that the best dose of each drug can be determined. This combination product should only be used if your doctor determines that the doses of each drug in this product are right for your condition. Depending on your condition, your medications may need to be adjusted by your doctor on an ongoing basis.

USES: Amiloride is used with hydrochlorothiazide to treat high blood pressure (hypertension), certain heart problems (congestive heart failure) or swelling (edema) that may be caused by severe liver problems.

Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. Controlling congestive heart failure helps prevent a worsening of the disease and its symptoms, such as tiredness, difficulty breathing, and swelling (edema).

This medication contains two drugs, amiloride and hydrochlorothiazide. Each medication is a water pill (diuretic) that works by increasing the amount of urine you make, allowing your body to get rid of extra salt and water. Amiloride also prevents the kidneys from getting rid of too much potassium.

HOW TO USE: See also the Warning section.

Take this medication by mouth, usually once daily on an empty stomach or as directed by your doctor. If stomach upset occurs, take it with food, but consistently take it either with or without food.

If you take this drug too close to bedtime, you may need to wake up to urinate. Therefore, it is best to take this medication at least 4 hours before your bedtime.

The dosage is based on your age, medical condition and response to therapy. If you have severe liver or kidney problems, your dosage may need to be adjusted.

Use this medication regularly in order to get the most benefit from it. To help you remember, take it at the same time each day. It is important to continue taking this medication even if you feel well. Most people with high blood pressure do not feel sick. It may take up to several weeks before the full benefit of this drug takes effect.

Do not stop taking this medication without first consulting your doctor. Some conditions may become worse when the drug is abruptly stopped. Your dose may need to be gradually decreased.

Inform your doctor if your condition worsens (e.g., your routine blood pressure readings increase).

SIDE EFFECTS: See also the Warning section.

Headache, weakness, increased tiredness, dizziness, nausea, decreased appetite, vomiting, diarrhea, or intestinal gas may occur as your body adjusts to the medication. You may also be more sensitive to sunburn (see Precautions section). If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

This medication may cause too much body water and salts to be lost (dehydration). Tell your doctor immediately if you have any of these unlikely but serious symptoms of dehydration: very dry mouth, thirst, muscle cramps, weakness, fast heartbeat, vomiting, severe dizziness, confusion, unusual decrease in the amount of urine, fainting, seizures.

Tell your doctor immediately if any of these unlikely but serious side effects occur: joint/muscle pain, worsening of gout, flushing, unusual tiredness, mental/mood changes (e.g., depression), rapid breathing, decreased sexual ability, vision changes (yellow vision), tingling of the hands/feet, ringing in the ears.

Tell your doctor immediately if any of these rare but very serious side effects occur: easy bruising/bleeding, signs of infection (e.g., fever, persistent sore throat), yellowing eyes/skin, persistent nausea/vomiting, severe stomach/abdominal pain, dark urine, black stools.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking this product, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medication, consult your doctor or pharmacist if you have: inability to make urine (anuria), severe kidney problems (e.g., acute or chronic renal failure, diabetic nephropathy), high blood potassium levels (hyperkalemia).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: diabetes, severe liver problems (e.g., cirrhosis, hepatic encephalopathy), heart disease, untreated blood salt problems (e.g., low sodium), other kidney problems, high cholesterol or blood fats (triglycerides), lupus, gout, recent nerve surgery, asthma.

Before having surgery, tell your doctor or dentist that you are taking this medication.

This drug may make you dizzy; use caution while engaging in activities requiring alertness such as driving or using machinery. Limit alcoholic beverages.

To reduce dizziness and lightheadedness, get up slowly when rising from a sitting or lying position, and drink plenty of fluids unless your doctor directs you otherwise. Too much sweating, diarrhea or vomiting may cause you to lose large amounts of water and salts, causing lightheadedness. Avoid heavy exercise. Report prolonged diarrhea or vomiting to your doctor.

Caution is advised when using this drug in the elderly because they may be more sensitive to its effects, especially dizziness and lightheadedness. The elderly are also more likely to have kidney problems and be at risk for high potassium levels.

This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths, and sunlamps. Use a sunscreen and wear protective clothing when outdoors.

If you have diabetes, this product may make it harder to control your blood sugar levels. Check your blood sugar levels regularly as directed by your doctor. Tell your doctor immediately if you have symptoms of high blood sugar such as increased thirst and urination. Your anti-diabetic medication or diet may need to be adjusted.

This product should be used only when clearly needed during pregnancy. Babies born to mothers who have taken this medication during pregnancy may be at risk for liver problems and bleeding problems. Discuss the risks and benefits with your doctor.

The hydrochlorothiazide in this product passes into breast milk. It is not known if the amiloride in this product passes into breast milk. Breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medication because very serious interactions may occur: dofetilide.

If you are currently using this medication listed above, tell your doctor or pharmacist before starting this product.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: alcohol, cisapride, drugs that may lower your blood pressure (e.g., barbiturates such as phenobarbital, guanethidine, methyldopa, narcotic pain relievers such as codeine), drugs for diabetes (e.g., glyburide, insulin), diazoxide, digoxin, drugs that may be harmful to your kidneys (e.g., cyclosporine), lithium, probenecid, tacrolimus, tubocurarine, drugs whose removal from the body is affected by acid levels of urine (e.g., amphetamine, methenamine, quinidine), other products that may decrease potassium levels (e.g., amphotericin B, corticotropin, corticosteroids including prednisone), other products that may increase potassium levels (e.g., eplerenone, spironolactone, triamterene, potassium supplements, salt substitutes containing potassium, ACE inhibitors including benazepril and captopril, angiotensin receptor antagonists including losartan and valsartan).

Cholestyramine and colestipol may decrease the absorption of this medication. If you are taking either of these drugs, separate them from this medication by at least 4 hours.

Check the labels on all your medicines (e.g., cough-and-cold products, diet aids, nonsteroidal anti-inflammatory drugs-NSAIDs for pain/fever reduction) because they may contain ingredients that could increase your blood pressure (e.g., pseudoephedrine, phenylephrine, chlorpheniramine, diphenhydramine, clemastine, ibuprofen, naproxen). Ask your pharmacist about using those products safely.

This product can affect the results of certain lab tests (glucose tolerance testing, parathyroid test). Make sure laboratory personnel and all your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly.

NOTES: Do not share this medication with others.

If you have high blood pressure, lifestyle changes such as stress reduction programs, exercise, and dietary changes may increase the effectiveness of this medicine. Talk to your doctor or pharmacist about lifestyle changes that might benefit you.

Laboratory and/or medical tests (e.g., kidney and liver function, blood salt levels, complete blood counts, cholesterol) should be performed regularly to monitor your progress or check for side effects. Consult your doctor for more details.

Have your blood pressure and heart rate checked regularly while taking this medication. Learn how to monitor your own blood pressure and heart rate at home, and share the readings with your doctor.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For enrollment information call MedicAlert at 1-800-854- 1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.