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Moduret (Hydrochlorothiazide Amiloride HCl)
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Pharmacology
Moduret is a diuretic/antihypertensive combining the potent natriuretic action of hydrochlorothiazide with the potassium-conserving property of amiloride. The mild diuretic and antihypertensive actions of amiloride are additive to the natriuretic, diuretic and antihypertensive activity of the thiazide while minimizing the loss of potassium and bicarbonate and lessening the likelihood of acid base imbalance. The onset of the diuretic action is within 1to 2hours and this action appears to be sustained for approximately 24hours.
Hydrochlorothiazide: Hydrochlorothiazide is a diuretic and antihypertensive agent. It affects the 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. While this compound is predominantly a saluretic agent, in vitro studies have shown that it has a carbonic anhydrase inhibitory action which seems to be relatively specific for the renal tubular mechanism. It does not appear to be concentrated in erythrocytes or the brain in sufficient amounts to influence the activity of carbonic anhydrase in those tissues.
Hydrochlorothiazide is useful in the treatment of hypertension. It may be used alone or as an adjunct to other antihypertensive drugs.
Hydrochlorothiazide does not decrease normal blood pressure.
The onset of the diuretic action of hydrochlorothiazide occurs in 2hours and the peak action in about 4hours. Diuretic activity lasts about 6to 12hours.
Amiloride: Amiloride is an antikaliuretic drug with mild natriuretic diuretic and antihypertensive activity. These activities may be additive to the effects of thiazides or other saluretic-diuretic agents. The principal use of amiloride is to conserve potassium in selected patients receiving kaliuretic-diuretic agents. The action is not related to the level of aldosterone excretion. Amiloride is not an aldosterone antagonist. The drug acts directly on the distal portion of the nephron. Amiloride causes an increase in sodium excretion and a decrease in potassium and hydrogen ion excretion. Chloride excretion may remain unchanged or increase slowly with continued therapy.
Approximately 50% of an oral dose is absorbed. Amiloride usually begins to act within 2hours after an oral dose. Its effect on electrolyte excretion reaches a peak between 6and 10hours and lasts about 24hours.
Pharmacokinetics: Amiloride: Peak plasma levels are obtained in 3to 4hours and plasma half-life varies from 6to 9hours.
Amiloride is not metabolized by the liver. About 50% of a 20mg dose of amiloride is excreted unchanged in the urine and 40% is excreted in the stool within 72hours. In clinical studies amiloride was found to have little effect on glomerular filtration rate or renal blood flow.
Hydrochlorothiazide: Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney. The plasma half-life is 5.6 to 14.8 hours when the plasma levels can be followed for at least 24hours. At least 61% of the oral dose is eliminated unchanged within 24hours. Hydrochlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.
Moduret is a diuretic/antihypertensive combining the potent natriuretic action of hydrochlorothiazide with the potassium-conserving property of amiloride. The mild diuretic and antihypertensive actions of amiloride are additive to the natriuretic, diuretic and antihypertensive activity of the thiazide while minimizing the loss of potassium and bicarbonate and lessening the likelihood of acid base imbalance. The onset of the diuretic action is within 1to 2hours and this action appears to be sustained for approximately 24hours.
Hydrochlorothiazide: Hydrochlorothiazide is a diuretic and antihypertensive agent. It affects the 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. While this compound is predominantly a saluretic agent, in vitro studies have shown that it has a carbonic anhydrase inhibitory action which seems to be relatively specific for the renal tubular mechanism. It does not appear to be concentrated in erythrocytes or the brain in sufficient amounts to influence the activity of carbonic anhydrase in those tissues.
Hydrochlorothiazide is useful in the treatment of hypertension. It may be used alone or as an adjunct to other antihypertensive drugs.
Hydrochlorothiazide does not decrease normal blood pressure.
The onset of the diuretic action of hydrochlorothiazide occurs in 2hours and the peak action in about 4hours. Diuretic activity lasts about 6to 12hours.
Amiloride: Amiloride is an antikaliuretic drug with mild natriuretic diuretic and antihypertensive activity. These activities may be additive to the effects of thiazides or other saluretic-diuretic agents. The principal use of amiloride is to conserve potassium in selected patients receiving kaliuretic-diuretic agents. The action is not related to the level of aldosterone excretion. Amiloride is not an aldosterone antagonist. The drug acts directly on the distal portion of the nephron. Amiloride causes an increase in sodium excretion and a decrease in potassium and hydrogen ion excretion. Chloride excretion may remain unchanged or increase slowly with continued therapy.
Approximately 50% of an oral dose is absorbed. Amiloride usually begins to act within 2hours after an oral dose. Its effect on electrolyte excretion reaches a peak between 6and 10hours and lasts about 24hours.
Pharmacokinetics: Amiloride: Peak plasma levels are obtained in 3to 4hours and plasma half-life varies from 6to 9hours.
Amiloride is not metabolized by the liver. About 50% of a 20mg dose of amiloride is excreted unchanged in the urine and 40% is excreted in the stool within 72hours. In clinical studies amiloride was found to have little effect on glomerular filtration rate or renal blood flow.
Hydrochlorothiazide: Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney. The plasma half-life is 5.6 to 14.8 hours when the plasma levels can be followed for at least 24hours. At least 61% of the oral dose is eliminated unchanged within 24hours. Hydrochlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.
Indications
Moduret Is A Diuretic/antihypertensive Combining The Potent Natriuretic Action Of Hydrochlorothiazide With The Potassium-conserving Property Of Amiloride. The Mild Diuretic And Antihypertensive Actions Of Amiloride Are Additive To The Natriuretic, Diuretic And Antihypertensive Activity Of The Thiazide While Minimizing The Loss Of Potassium And Bicarbonate And Lessening The Likelihood Of Acid Base Imbalance. The Onset Of The Diuretic Action Is Within 1to 2hours And This Action Appears To Be Sustained For Approximately 24hours.
Hydrochlorothiazide: Hydrochlorothiazide Is A Diuretic And Antihypertensive Agent. It Affects The 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. While This Compound Is Predominantly A Saluretic Agent, In Vitro Studies Have Shown That It Has A Carbonic Anhydrase Inhibitory Action Which Seems To Be Relatively Specific For The Renal Tubular Mechanism. It Does Not Appear To Be Concentrated In Erythrocytes Or The Brain In Sufficient Amounts To Influence The Activity Of Carbonic Anhydrase In Those Tissues.
Hydrochlorothiazide Is Useful In The Treatment Of Hypertension. It May Be Used Alone Or As An Adjunct To Other Antihypertensive Drugs.
Hydrochlorothiazide Does Not Decrease Normal Blood Pressure.
The Onset Of The Diuretic Action Of Hydrochlorothiazide Occurs In 2hours And The Peak Action In About 4hours. Diuretic Activity Lasts About 6to 12hours.
Amiloride: Amiloride Is An Antikaliuretic Drug With Mild Natriuretic Diuretic And Antihypertensive Activity. These Activities May Be Additive To The Effects Of Thiazides Or Other Saluretic-diuretic Agents. The Principal Use Of Amiloride Is To Conserve Potassium In Selected Patients Receiving Kaliuretic-diuretic Agents. The Action Is Not Related To The Level Of Aldosterone Excretion. Amiloride Is Not An Aldosterone Antagonist. The Drug Acts Directly On The Distal Portion Of The Nephron. Amiloride Causes An Increase In Sodium Excretion And A Decrease In Potassium And Hydrogen Ion Excretion. Chloride Excretion May Remain Unchanged Or Increase Slowly With Continued Therapy.
Approximately 50% Of An Oral Dose Is Absorbed. Amiloride Usually Begins To Act Within 2hours After An Oral Dose. Its Effect On Electrolyte Excretion Reaches A Peak Between 6and 10hours And Lasts About 24hours.
Pharmacokinetics: Amiloride: Peak Plasma Levels Are Obtained In 3to 4hours And Plasma Half-life Varies From 6to 9hours.
Amiloride Is Not Metabolized By The Liver. About 50% Of A 20mg Dose Of Amiloride Is Excreted Unchanged In The Urine And 40% Is Excreted In The Stool Within 72hours. In Clinical Studies Amiloride Was Found To Have Little Effect On Glomerular Filtration Rate Or Renal Blood Flow.
Hydrochlorothiazide: Hydrochlorothiazide Is Not Metabolized But Is Eliminated Rapidly By The Kidney. The Plasma Half-life Is 5.6 To 14.8 Hours When The Plasma Levels Can Be Followed For At Least 24hours. At Least 61% Of The Oral Dose Is Eliminated Unchanged Within 24hours. Hydrochlorothiazide Crosses The Placental But Not The Blood-brain Barrier And Is Excreted In Breast Milk.
Moduret Is A Diuretic/antihypertensive Combining The Potent Natriuretic Action Of Hydrochlorothiazide With The Potassium-conserving Property Of Amiloride. The Mild Diuretic And Antihypertensive Actions Of Amiloride Are Additive To The Natriuretic, Diuretic And Antihypertensive Activity Of The Thiazide While Minimizing The Loss Of Potassium And Bicarbonate And Lessening The Likelihood Of Acid Base Imbalance. The Onset Of The Diuretic Action Is Within 1to 2hours And This Action Appears To Be Sustained For Approximately 24hours.
Hydrochlorothiazide: Hydrochlorothiazide Is A Diuretic And Antihypertensive Agent. It Affects The 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. While This Compound Is Predominantly A Saluretic Agent, In Vitro Studies Have Shown That It Has A Carbonic Anhydrase Inhibitory Action Which Seems To Be Relatively Specific For The Renal Tubular Mechanism. It Does Not Appear To Be Concentrated In Erythrocytes Or The Brain In Sufficient Amounts To Influence The Activity Of Carbonic Anhydrase In Those Tissues.
Hydrochlorothiazide Is Useful In The Treatment Of Hypertension. It May Be Used Alone Or As An Adjunct To Other Antihypertensive Drugs.
Hydrochlorothiazide Does Not Decrease Normal Blood Pressure.
The Onset Of The Diuretic Action Of Hydrochlorothiazide Occurs In 2hours And The Peak Action In About 4hours. Diuretic Activity Lasts About 6to 12hours.
Amiloride: Amiloride Is An Antikaliuretic Drug With Mild Natriuretic Diuretic And Antihypertensive Activity. These Activities May Be Additive To The Effects Of Thiazides Or Other Saluretic-diuretic Agents. The Principal Use Of Amiloride Is To Conserve Potassium In Selected Patients Receiving Kaliuretic-diuretic Agents. The Action Is Not Related To The Level Of Aldosterone Excretion. Amiloride Is Not An Aldosterone Antagonist. The Drug Acts Directly On The Distal Portion Of The Nephron. Amiloride Causes An Increase In Sodium Excretion And A Decrease In Potassium And Hydrogen Ion Excretion. Chloride Excretion May Remain Unchanged Or Increase Slowly With Continued Therapy.
Approximately 50% Of An Oral Dose Is Absorbed. Amiloride Usually Begins To Act Within 2hours After An Oral Dose. Its Effect On Electrolyte Excretion Reaches A Peak Between 6and 10hours And Lasts About 24hours.
Pharmacokinetics: Amiloride: Peak Plasma Levels Are Obtained In 3to 4hours And Plasma Half-life Varies From 6to 9hours.
Amiloride Is Not Metabolized By The Liver. About 50% Of A 20mg Dose Of Amiloride Is Excreted Unchanged In The Urine And 40% Is Excreted In The Stool Within 72hours. In Clinical Studies Amiloride Was Found To Have Little Effect On Glomerular Filtration Rate Or Renal Blood Flow.
Hydrochlorothiazide: Hydrochlorothiazide Is Not Metabolized But Is Eliminated Rapidly By The Kidney. The Plasma Half-life Is 5.6 To 14.8 Hours When The Plasma Levels Can Be Followed For At Least 24hours. At Least 61% Of The Oral Dose Is Eliminated Unchanged Within 24hours. Hydrochlorothiazide Crosses The Placental But Not The Blood-brain Barrier And Is Excreted In Breast Milk.
Contraindications
Hyperkalemia: Moduret should not be used in the presence of elevated serum potassium levels.
Antikaliuretic Therapy or Potassium Salts: Other antikaliuretic agents and potassium supplements are contraindicated in patients receiving Moduret (such combination therapy is commonly associated with rapid increases in plasma potassium levels).
Impaired Renal Function: Anuria, acute renal failure, severe or progressive renal disease, and diabetic nephropathy are contraindications to the use of Moduret.
Safety Information / Warning
Hyperkalemia: Hyperkalemia, i.e., serum potassium levels over 5.5mEq/L, has been observed in some patients who received amiloride either alone or with diuretics. This has been noted particularly in elderly patients, in diabetic patients, and in hospitalized patients with hepatic cirrhosis or cardiac edema who had known renal impairment, were seriously ill, or were receiving vigorous diuretic therapy. Since fatalities have occurred in such patients, they should be monitored carefully for clinical, laboratory, and electrocardiographic (ECG) evidence of hyperkalemia and for acidosis. Monitoring of the serum potassium level is important because hyperkalemia is not always associated with an abnormal ECG.
Warning signs and symptoms of hyperkalemia include paresthesias, muscular weakness, fatigue, flaccid paralysis of the extremities, bradycardia, shock and ECG abnormalities.
When abnormal, the ECG in hyperkalemia is characterized primarily by tall, peaked Twaves or elevations from previous tracings. There may also be lowering of the Rwave and increased depth of the Swave, widening and even disappearance of the Pwave, progressive widening of the QRS complex, prolongation of the PR interval, and ST depression.
Potassium supplementation in the form of medication or a potassium-rich diet should not be used with Moduret except in severe and/or refractory cases of hypokalemia. If potassium supplementation is used, careful monitoring of the serum potassium level is recommended.
Treatment of Hyperkalemia: If hyperkalemia occurs in patients taking Moduret the drug should be discontinued immediately. If the serum potassium level exceeds 6.5mEq/L, active measures should be taken to reduce it. Such measures include the i.v. 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 commonly reported with the use of amiloride, particularly if they have chronic renal disease or prerenal azotemia. Some deaths occurred in this last group of patients. Therefore, if therapy with amiloride is considered essential, the drug should be used with caution in diabetic or suspected diabetic patients and only after first determining the status of renal function.
Careful monitoring of serum potassium levels is required throughout the therapy.
One patient with poorly controlled diabetes mellitus who became severely hyperkalemic while on amiloride died following 2repeated i.v. glucose tolerance tests. Therefore, amiloride should be discontinued at least 3days before glucose tolerance testing.
In diabetic patients, insulin requirements may be increased, decreased, or unchanged due to the hydrochlorothiazide component. Diabetes mellitus which has been latent may become manifest during administration of thiazide diuretics.
Metabolic or Respiratory Acidosis: Antikaliuretic therapy should be instituted only with caution in patients in whom respiratory or metabolic acidosis may occur, such as patients with cardiopulmonary disease or diabetes. If Moduret is given to the 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.
Impaired Renal Function and/or Azotemia: When creatinine clearance falls below 30 mL/min thiazide diuretics are ineffective.
In patients with impaired renal function azotemia may be precipitated or increased by hydrochlorothiazide. Cumulative effects of the drug may develop in patients with impaired renal function. Careful monitoring of such patients is therefore necessary. If increasing azotemia and oliguria occur during treatment Moduret should be discontinued.
Patients with impaired renal function other than those listed under Contraindications and who have BUN levels over 30mg/100mL, serum creatinine levels over 1.5mg/100mL, or blood urea values over 60mg/100mL should not receive the drug without careful, frequent monitoring of serum electrolytes, creatinine, and BUN levels. Potassium retention associated with the use of Moduret is accentuated in the presence of renal impairment and may result in the rapid development of hyperkalemia. Prolongation of amiloride excretion was observed in patients with renal impairment.
Hepatic Disease: Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
Hypersensitivity Reactions: Sensitivity reactions to thiazides may occur in patients 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 thiazides.
Hyperkalemia: Hyperkalemia, i.e., serum potassium levels over 5.5mEq/L, has been observed in some patients who received amiloride either alone or with diuretics. This has been noted particularly in elderly patients, in diabetic patients, and in hospitalized patients with hepatic cirrhosis or cardiac edema who had known renal impairment, were seriously ill, or were receiving vigorous diuretic therapy. Since fatalities have occurred in such patients, they should be monitored carefully for clinical, laboratory, and electrocardiographic (ECG) evidence of hyperkalemia and for acidosis. Monitoring of the serum potassium level is important because hyperkalemia is not always associated with an abnormal ECG.
Warning signs and symptoms of hyperkalemia include paresthesias, muscular weakness, fatigue, flaccid paralysis of the extremities, bradycardia, shock and ECG abnormalities.
When abnormal, the ECG in hyperkalemia is characterized primarily by tall, peaked Twaves or elevations from previous tracings. There may also be lowering of the Rwave and increased depth of the Swave, widening and even disappearance of the Pwave, progressive widening of the QRS complex, prolongation of the PR interval, and ST depression.
Potassium supplementation in the form of medication or a potassium-rich diet should not be used with Moduret except in severe and/or refractory cases of hypokalemia. If potassium supplementation is used, careful monitoring of the serum potassium level is recommended.
Treatment of Hyperkalemia: If hyperkalemia occurs in patients taking Moduret the drug should be discontinued immediately. If the serum potassium level exceeds 6.5mEq/L, active measures should be taken to reduce it. Such measures include the i.v. 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 commonly reported with the use of amiloride, particularly if they have chronic renal disease or prerenal azotemia. Some deaths occurred in this last group of patients. Therefore, if therapy with amiloride is considered essential, the drug should be used with caution in diabetic or suspected diabetic patients and only after first determining the status of renal function.
Careful monitoring of serum potassium levels is required throughout the therapy.
One patient with poorly controlled diabetes mellitus who became severely hyperkalemic while on amiloride died following 2repeated i.v. glucose tolerance tests. Therefore, amiloride should be discontinued at least 3days before glucose tolerance testing.
In diabetic patients, insulin requirements may be increased, decreased, or unchanged due to the hydrochlorothiazide component. Diabetes mellitus which has been latent may become manifest during administration of thiazide diuretics.
Metabolic or Respiratory Acidosis: Antikaliuretic therapy should be instituted only with caution in patients in whom respiratory or metabolic acidosis may occur, such as patients with cardiopulmonary disease or diabetes. If Moduret is given to the 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.
Impaired Renal Function and/or Azotemia: When creatinine clearance falls below 30 mL/min thiazide diuretics are ineffective.
In patients with impaired renal function azotemia may be precipitated or increased by hydrochlorothiazide. Cumulative effects of the drug may develop in patients with impaired renal function. Careful monitoring of such patients is therefore necessary. If increasing azotemia and oliguria occur during treatment Moduret should be discontinued.
Patients with impaired renal function other than those listed under Contraindications and who have BUN levels over 30mg/100mL, serum creatinine levels over 1.5mg/100mL, or blood urea values over 60mg/100mL should not receive the drug without careful, frequent monitoring of serum electrolytes, creatinine, and BUN levels. Potassium retention associated with the use of Moduret is accentuated in the presence of renal impairment and may result in the rapid development of hyperkalemia. Prolongation of amiloride excretion was observed in patients with renal impairment.
Hepatic Disease: Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
Hypersensitivity Reactions: Sensitivity reactions to thiazides may occur in patients 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 thiazides.
Precautions
Electrolyte Imbalance and BUN Increases: Although the likelihood of electrolyte imbalance is lessened with Moduret, careful check should be kept for signs of fluid and electrolyte imbalance: namely, hyponatremia, hypochloremic alkalosis, hypokalemia and hypomagnesemia. It is particularly important to make serum and urine electrolyte determinations when the patient is vomiting excessively or receiving parenteral fluids. Warning signs or symptoms of fluid and electrolyte imbalance include: dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, seizures, confusion, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.
Hypokalemia may develop with hydrochlorothiazide as with any other potent diuretic, especially with brisk diuresis, after prolonged therapy or when severe cirrhosis is present. Hypokalemia can sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability).
Diuretic induced hyponatremia is usually mild and asymptomatic. In a few patients hyponatremia may become severe and symptomatic. Such patients require immediate attention and appropriate treatment.
Hypochloremia may occur during the use of Moduret. Any chloride deficit is usually mild and may be corrected by the use of ammonium chloride (except in patients with hepatic disease) and largely prevented by a near normal salt intake. Increases in BUN levels have been reported and have usually accompanied vigorous fluid elimination, especially when diuretic combinations were used in seriously ill patients, such as those who have hepatic cirrhosis with ascites and metabolic alkalosis, or those with resistant edema. Therefore, careful monitoring of serum electrolytes and BUN levels is important when using Moduret.
Effects Related to Diuresis in Cirrhotic Patients: Patients with hepatic cirrhosis and ascites are intolerant of acute shifts in electrolyte balance and often have pre-existing hypokalemia as a result of associated secondary hyperaldosteronism. When oral diuretic therapy is used, these patients should be carefully monitored and diuresis should be gradual.
Hepatic encephalopathy, manifested by tremors, confusion, and coma, has been reported in association with amiloride therapy.
In cirrhotic patients receiving amiloride alone, jaundice associated with the underlying disease process has deepened in a few instances, but the relationship to the drug is uncertain.
Metabolism: Hyperuricemia may occur or gout may be precipitated in certain patients receiving thiazide therapy.
Thiazides may decrease serum PBI levels without signs of thyroid disturbance.
Magnesium excretion is increased. This may result in hypomagnesemia.
Thiazide may decrease urinary calcium excretion. Thiazides may cause intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Marked hypercalcemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued before carrying out test for parathyroid function.
Increases in cholesterol and triglycerides levels may be associated with thiazide diuretic therapy.
Other: Patients should be observed regularly for the possible occurrence of liver dysfunction, idiosyncratic reactions, or blood dyscrasias.
Pregnancy : Because clinical experience is limited, Moduret is not recommended for use during pregnancy.
The routine use of diuretics in otherwise healthy pregnant women with or without mild edema is not recommended and exposes mother and fetus to unnecessary hazard. Diuretics do not prevent development of toxemia of pregnancy and there is no satisfactory evidence that they are useful in the treatment of toxemia.
Teratologic studies with amiloride in rabbits and mice revealed no evidence of harm to the fetus. Reproduction studies in rats showed no evidence of impaired fertility. At approximately 5or 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.
In rats a trace of drug crossed the placental barrier.
Thiazides cross the placental barrier and appear in the cord blood. Therefore, the use of Moduret when pregnancy is present or suspected requires that the benefits of the drug be weighed against possible hazards to the fetus. These hazards include fetal or neonatal jaundice, thrombocytopenia and possibly other side effects that have occurred in the adult.
Lactation: It is not known whether amiloride is excreted in human milk. In rats secretion of amiloride in milk has been demonstrated. Thiazides appear in breast milk. Because of the potential for serious adverse reactions in nursing infants, if the use of Moduret is deemed essential, the patient should stop nursing.
Children: The safety for use of amiloride in children has not been established; therefore, Moduret is not recommended in the pediatric age group.
Drug Interactions : Lithium: Lithium should generally not be given to patients receiving diuretics. Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity; concomitant use is not recommended. Refer to the Product Monograph for lithium preparations before use of such preparations.
NSAIDs: In some patients, the administration of an NSAID can reduce the diuretic, natriuretic and hypertensive effects of diuretics. Concomitant administration of NSAIDs and potassium-sparing agents, including amiloride, may cause hyperkalemia and renal failure, particularly in elderly patients. Therefore, when amiloride is used concomitantly with NSAIDs, renal function and serum potassium levels should be carefully monitored.
Others: When amiloride hydrochloride is administered concomitantly with an angiotensin-converting enzyme inhibitor, cyclosporine, 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.
When given concurrently the following drugs may interact with thiazide diuretics.
Other Antihypertensive Drugs: Hydrochlorothiazide potentiates the action of other antihypertensive drugs. Therefore, the dosage of these agents, especially the ganglion blockers, may need to be reduced when Moduret is added to the regimen.
Skeletal Muscle Relaxants, Nondepolarizing: Thiazide-containing drugs may increase the responsiveness to tubocurarine.
Pressor Amines: Hydrochlorothiazide may decrease arterial responsiveness to norepinephrine. This diminution is not sufficient to preclude the effectiveness of the pressor agent for therapeutic use.
Alcohol, Barbiturates, or Narcotics: In the presence of thiazide diuretics, potentiation of orthostatic hypotension may occur.
Antidiabetic Drugs (Oral Agents and Insulin): Dosage adjustment of the antidiabetic drug may be required. Insulin requirements in diabetic patients treated with thiazide diuretics may be increased. Diabetes mellitus which has been latent may become manifest during thiazide administration.
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% respectively.
Corticosteroids, ACTH: Intensified electrolyte depletion, particularly hypokalemia may occur when given concomitantly with thiazide diuretics.
Drug/Laboratory Test Interactions : Because of their effects on calcium metabolism, thiazides may interfere with tests for parathyroid function.
Electrolyte Imbalance and BUN Increases: Although the likelihood of electrolyte imbalance is lessened with Moduret, careful check should be kept for signs of fluid and electrolyte imbalance: namely, hyponatremia, hypochloremic alkalosis, hypokalemia and hypomagnesemia. It is particularly important to make serum and urine electrolyte determinations when the patient is vomiting excessively or receiving parenteral fluids. Warning signs or symptoms of fluid and electrolyte imbalance include: dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, seizures, confusion, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.
Hypokalemia may develop with hydrochlorothiazide as with any other potent diuretic, especially with brisk diuresis, after prolonged therapy or when severe cirrhosis is present. Hypokalemia can sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability).
Diuretic induced hyponatremia is usually mild and asymptomatic. In a few patients hyponatremia may become severe and symptomatic. Such patients require immediate attention and appropriate treatment.
Hypochloremia may occur during the use of Moduret. Any chloride deficit is usually mild and may be corrected by the use of ammonium chloride (except in patients with hepatic disease) and largely prevented by a near normal salt intake. Increases in BUN levels have been reported and have usually accompanied vigorous fluid elimination, especially when diuretic combinations were used in seriously ill patients, such as those who have hepatic cirrhosis with ascites and metabolic alkalosis, or those with resistant edema. Therefore, careful monitoring of serum electrolytes and BUN levels is important when using Moduret.
Effects Related to Diuresis in Cirrhotic Patients: Patients with hepatic cirrhosis and ascites are intolerant of acute shifts in electrolyte balance and often have pre-existing hypokalemia as a result of associated secondary hyperaldosteronism. When oral diuretic therapy is used, these patients should be carefully monitored and diuresis should be gradual.
Hepatic encephalopathy, manifested by tremors, confusion, and coma, has been reported in association with amiloride therapy.
In cirrhotic patients receiving amiloride alone, jaundice associated with the underlying disease process has deepened in a few instances, but the relationship to the drug is uncertain.
Metabolism: Hyperuricemia may occur or gout may be precipitated in certain patients receiving thiazide therapy.
Thiazides may decrease serum PBI levels without signs of thyroid disturbance.
Magnesium excretion is increased. This may result in hypomagnesemia.
Thiazide may decrease urinary calcium excretion. Thiazides may cause intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Marked hypercalcemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued before carrying out test for parathyroid function.
Increases in cholesterol and triglycerides levels may be associated with thiazide diuretic therapy.
Other: Patients should be observed regularly for the possible occurrence of liver dysfunction, idiosyncratic reactions, or blood dyscrasias.
Pregnancy : Because clinical experience is limited, Moduret is not recommended for use during pregnancy.
The routine use of diuretics in otherwise healthy pregnant women with or without mild edema is not recommended and exposes mother and fetus to unnecessary hazard. Diuretics do not prevent development of toxemia of pregnancy and there is no satisfactory evidence that they are useful in the treatment of toxemia.
Teratologic studies with amiloride in rabbits and mice revealed no evidence of harm to the fetus. Reproduction studies in rats showed no evidence of impaired fertility. At approximately 5or 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.
In rats a trace of drug crossed the placental barrier.
Thiazides cross the placental barrier and appear in the cord blood. Therefore, the use of Moduret when pregnancy is present or suspected requires that the benefits of the drug be weighed against possible hazards to the fetus. These hazards include fetal or neonatal jaundice, thrombocytopenia and possibly other side effects that have occurred in the adult.
Lactation: It is not known whether amiloride is excreted in human milk. In rats secretion of amiloride in milk has been demonstrated. Thiazides appear in breast milk. Because of the potential for serious adverse reactions in nursing infants, if the use of Moduret is deemed essential, the patient should stop nursing.
Children: The safety for use of amiloride in children has not been established; therefore, Moduret is not recommended in the pediatric age group.
Drug Interactions : Lithium: Lithium should generally not be given to patients receiving diuretics. Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity; concomitant use is not recommended. Refer to the Product Monograph for lithium preparations before use of such preparations.
NSAIDs: In some patients, the administration of an NSAID can reduce the diuretic, natriuretic and hypertensive effects of diuretics. Concomitant administration of NSAIDs and potassium-sparing agents, including amiloride, may cause hyperkalemia and renal failure, particularly in elderly patients. Therefore, when amiloride is used concomitantly with NSAIDs, renal function and serum potassium levels should be carefully monitored.
Others: When amiloride hydrochloride is administered concomitantly with an angiotensin-converting enzyme inhibitor, cyclosporine, 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.
When given concurrently the following drugs may interact with thiazide diuretics.
Other Antihypertensive Drugs: Hydrochlorothiazide potentiates the action of other antihypertensive drugs. Therefore, the dosage of these agents, especially the ganglion blockers, may need to be reduced when Moduret is added to the regimen.
Skeletal Muscle Relaxants, Nondepolarizing: Thiazide-containing drugs may increase the responsiveness to tubocurarine.
Pressor Amines: Hydrochlorothiazide may decrease arterial responsiveness to norepinephrine. This diminution is not sufficient to preclude the effectiveness of the pressor agent for therapeutic use.
Alcohol, Barbiturates, or Narcotics: In the presence of thiazide diuretics, potentiation of orthostatic hypotension may occur.
Antidiabetic Drugs (Oral Agents and Insulin): Dosage adjustment of the antidiabetic drug may be required. Insulin requirements in diabetic patients treated with thiazide diuretics may be increased. Diabetes mellitus which has been latent may become manifest during thiazide administration.
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% respectively.
Corticosteroids, ACTH: Intensified electrolyte depletion, particularly hypokalemia may occur when given concomitantly with thiazide diuretics.
Drug/Laboratory Test Interactions : Because of their effects on calcium metabolism, thiazides may interfere with tests for parathyroid function.
Side Effects / Adverse Effects
While rare, the most serious adverse effect is symptomatic hyperkalemia. Other metabolic changes that occur are asymptomatic hyperkalemia, hypokalemia and hypochloremia.
Other adverse reactions reported with Moduret are listed below:
Body as a Whole: syncope.
Metabolic: elevated serum potassium levels (>5.5 mEq/L), electrolyte imbalance, hyponatremia (see Precautions), symptomatic hyponatremia.
Integumentary: diaphoresis.
Urogenital: Renal dysfunction including renal failure.
Other adverse reactions that have been reported with the individual components are listed below:
Amiloride: Body as a Whole: neck/shoulder ache, pain in extremities.
Digestive: abnormal liver function, activation of pre-existing peptic ulcer, dyspepsia, jaundice.
Integumentary: dry mouth, alopecia.
Nervous: tremors, encephalopathy.
Hematologic: neutropenia, aplastic anemia.
Cardiovascular: One patient with a partial heart-block developed complete heart-block, palpitation.
Psychiatric: decreased libido, somnolence.
Respiratory: cough.
Special Senses: tinnitus, increased intraocular pressure.
Urogenital: polyuria, urinary frequency, bladder spasm.
Hydrochlorothiazide: Body as a Whole: anaphylactic reactions, fever.
Cardiovascular: necrotizing angiitis (vasculitis, cutaneous vasculitis).
Digestive: jaundice (intrahepatic cholestatic jaundice), pancreatitis, cramping, gastric irritation.
Endocrine/Metabolic: glycosuria, hyperglycemia, hyperuricemia, hypokalemia.
Hematologic: agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, purpura, thrombocytopenia.
Integumentary: photosensitivity, sialadenitis, urticaria, toxic-epidermal necrolysis.
Psychiatric: restlessness.
Renal: interstitial nephritis.
Respiratory: respiratory distress including pneumonitis and pulmonary edema.
Special Senses: transient blurred vision, xanthopsia.
While rare, the most serious adverse effect is symptomatic hyperkalemia. Other metabolic changes that occur are asymptomatic hyperkalemia, hypokalemia and hypochloremia.
Other adverse reactions reported with Moduret are listed below:
Body as a Whole: syncope.
Metabolic: elevated serum potassium levels (>5.5 mEq/L), electrolyte imbalance, hyponatremia (see Precautions), symptomatic hyponatremia.
Integumentary: diaphoresis.
Urogenital: Renal dysfunction including renal failure.
Other adverse reactions that have been reported with the individual components are listed below:
Amiloride: Body as a Whole: neck/shoulder ache, pain in extremities.
Digestive: abnormal liver function, activation of pre-existing peptic ulcer, dyspepsia, jaundice.
Integumentary: dry mouth, alopecia.
Nervous: tremors, encephalopathy.
Hematologic: neutropenia, aplastic anemia.
Cardiovascular: One patient with a partial heart-block developed complete heart-block, palpitation.
Psychiatric: decreased libido, somnolence.
Respiratory: cough.
Special Senses: tinnitus, increased intraocular pressure.
Urogenital: polyuria, urinary frequency, bladder spasm.
Hydrochlorothiazide: Body as a Whole: anaphylactic reactions, fever.
Cardiovascular: necrotizing angiitis (vasculitis, cutaneous vasculitis).
Digestive: jaundice (intrahepatic cholestatic jaundice), pancreatitis, cramping, gastric irritation.
Endocrine/Metabolic: glycosuria, hyperglycemia, hyperuricemia, hypokalemia.
Hematologic: agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, purpura, thrombocytopenia.
Integumentary: photosensitivity, sialadenitis, urticaria, toxic-epidermal necrolysis.
Psychiatric: restlessness.
Renal: interstitial nephritis.
Respiratory: respiratory distress including pneumonitis and pulmonary edema.
Special Senses: transient blurred vision, xanthopsia.
Overdose
Symptoms: No data are available in regard to overdosage in humans with Moduret or with the amiloride component.
The most common signs and symptoms to be expected from overdosage are dehydration and electrolyte imbalance. Serum electrolytes should be carefully monitored with special attention to potassium levels. If hyperkalemia occurs, active measures should be taken to reduce the serum potassium levels.
Cardiac arrhythmias may be caused by abnormal potassium levels. Digitalized patients are especially prone to arrhythmias.
Treatment: No specific information is available on the treatment of overdosage and no specific antidote is available. Treatment is symptomatic and supportive. Therapy with Moduret should be discontinued and the patient observed closely. Suggested measures include induction of emesis and/or gastric lavage.
It is not known whether the drug is dialyzable.
Symptoms: No data are available in regard to overdosage in humans with Moduret or with the amiloride component.
The most common signs and symptoms to be expected from overdosage are dehydration and electrolyte imbalance. Serum electrolytes should be carefully monitored with special attention to potassium levels. If hyperkalemia occurs, active measures should be taken to reduce the serum potassium levels.
Cardiac arrhythmias may be caused by abnormal potassium levels. Digitalized patients are especially prone to arrhythmias.
Treatment: No specific information is available on the treatment of overdosage and no specific antidote is available. Treatment is symptomatic and supportive. Therapy with Moduret should be discontinued and the patient observed closely. Suggested measures include induction of emesis and/or gastric lavage.
It is not known whether the drug is dialyzable.
Recommended Dosage
Optimal dosage should be established by the individual titration of the components.
Maintenance doses may be lower than those required to initiate diuresis; therefore, reduction in the daily dosage should be attempted when the patient's weight is stabilized. In cirrhotic patients, gradual weight reduction is especially desirable to reduce the likelihood of untoward reactions associated with diuretic therapy.
Hepatic Cirrhosis with Ascites and Edema: Maintenance: 1tablet once daily. The dosage should not exceed 4tablets a day in single or divided doses.
Edema of Cardiac Origin: Maintenance: 1or 2tablets given once daily or in divided doses. The dosage should not exceed 4tablets a day. Therapy may be on an intermittent basis.
Hypertension: Maintenance: 1or 2tablets once daily or in divided doses. The dosage should not exceed 4tablets a day.
Optimal dosage should be established by the individual titration of the components.
Maintenance doses may be lower than those required to initiate diuresis; therefore, reduction in the daily dosage should be attempted when the patient's weight is stabilized. In cirrhotic patients, gradual weight reduction is especially desirable to reduce the likelihood of untoward reactions associated with diuretic therapy.
Hepatic Cirrhosis with Ascites and Edema: Maintenance: 1tablet once daily. The dosage should not exceed 4tablets a day in single or divided doses.
Edema of Cardiac Origin: Maintenance: 1or 2tablets given once daily or in divided doses. The dosage should not exceed 4tablets a day. Therapy may be on an intermittent basis.
Hypertension: Maintenance: 1or 2tablets once daily or in divided doses. The dosage should not exceed 4tablets a day.
Supplied / Packaging
Each peach colored, diamond-shaped, compressed tablet, scored on one side with MSD917 and tradename MODURET on other, contains: hydrochlorothiazide 50mg and amiloride HCl 5mg. Nonmedicinal ingredients: dibasic calcium phosphate, guar gum, lactose, magnesium stearate, starch and sunset yellow FCF. Gluten- and tartrazine-free. Bottles of 100. Store between 15 and 30°C in a tightly closed container.
Each peach colored, diamond-shaped, compressed tablet, scored on one side with MSD917 and tradename MODURET on other, contains: hydrochlorothiazide 50mg and amiloride HCl 5mg. Nonmedicinal ingredients: dibasic calcium phosphate, guar gum, lactose, magnesium stearate, starch and sunset yellow FCF. Gluten- and tartrazine-free. Bottles of 100. Store between 15 and 30°C in a tightly closed container.
Search for a drug
Brand Name
Moduret
Moduret
Generic Name
Hydrochlorothiazide Amiloride HCl
Hydrochlorothiazide Amiloride HCl
General Indications
Diuretic Antihypertensive
Diuretic Antihypertensive
