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Chlorothiazide
Overview
What is Chlorothiazide?
Chlorothiazide is a diuretic and antihypertensive. It is 6-chloro-2-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is CHCINOS and its structural formula is:
It is a white, or practically white crystalline compound with a molecular weight of 295.72, which is very slightly soluble in water, but readily soluble in dilute aqueous sodium hydroxide. It is soluble in urine to the extent of about 150 mg per 100 mL at pH 7.
Chlorothiazide is supplied as 250 mg and 500 mg tablets, for oral use. Each tablet contains the following inactive ingredients: Anhydrous Lactose, Colloidal Silicon Dioxide, Magnesium Stearate, Microcrystalline Cellulose, Pregelatinized Starch, Polysorbate 80, and Sodium Starch Glycolate.
What does Chlorothiazide look like?
What are the available doses of Chlorothiazide?
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What should I talk to my health care provider before I take Chlorothiazide?
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How should I use Chlorothiazide?
Chlorothiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy.
Chlorothiazide has also been found useful in edema due to various forms of renal dysfunction such as nephrotic syndrome, acute glomerulonephritis, and chronic renal failure.
Chlorothiazide is indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension.
Therapy should be individualized according to patient response. Use the smallest dosage necessary to achieve the required response.
What interacts with Chlorothiazide?
Anuria.
Hypersensitivity to this product or to other sulfonamide-derived drugs.
What are the warnings of Chlorothiazide?
Prolonged use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to fungi or viruses.
Use with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.
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.
Thiazides may add to or potentiate the action of other antihypertensive drugs.
Sensitivity reactions 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.
Lithium generally should not be given with diuretics (see ).
What are the precautions of Chlorothiazide?
General
All patients receiving diuretic therapy should be observed for evidence of fluid or electrolyte imbalance: namely, 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.
Hypokalemia may develop, especially with brisk diuresis, when severe cirrhosis is present or after prolonged therapy.
Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Hypokalemia may cause cardiac arrhythmias and may also sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability). Hypokalemia may be avoided or treated by use of potassium sparing diuretics or potassium supplements such as foods with a high potassium content.
Although any chloride deficit is generally mild and usually does not require specific treatment except under extraordinary circumstances (as in liver disease or renal disease), chloride replacement may be required in the treatment of metabolic alkalosis.
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.
Hyperuricemia may occur or acute gout may be precipitated in certain patients receiving thiazides.
In diabetic patients dosage adjustments of insulin or oral hypoglycemic agents may be required. Hyperglycemia may occur with thiazide diuretics. Thus latent diabetes mellitus may become manifest during thiazide therapy.
The antihypertensive effects of the drug may be enhanced in the post-sympathectomy patient.
If progressive renal impairment becomes evident, consider withholding or discontinuing diuretic therapy.
Thiazides have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia.
Thiazides 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 tests for parathyroid function.
Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy.
Laboratory Tests
Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be done at appropriate intervals.
Drug Interactions
When given concurrently the following drugs may interact with thiazide diuretics.
Alcohol, barbiturates, or narcotics -
Antidiabetic drugs (oral agents and insulin) -
Other antihypertensive drugs -
Cholestyramine and colestipol resins -
Corticosteroids, ACTH -
Pressor amines (e.g., norepinephrine) -
Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine) -
Lithium -
Non-steroidal Anti-inflammatory Drugs -
Drug/Laboratory Test Interactions
Thiazides should be discontinued before carrying out tests for parathyroid function (see ).
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity and mutagenicity studies have not been conducted with chlorothiazide.
Chlorothiazide was not mutagenic in the Ames microbial mutagen test (using a maximum concentration of 5 mg/plate and strains TA98 and TA100) and was not mutagenic and did not induce mitotic non-disjunction in diploid-strains of .
Chlorothiazide had no adverse effects on fertility in female rats at doses up to 60 mg/kg/day and no adverse effects on fertility in male rats at doses up to 40 mg/kg/day. These doses are 1.5 and 1.0 times** the recommended maximum human dose, respectively, when compared on a body weight basis.
**Calculations based on a human body weight of 50 kg.
Pregnancy
Although reproduction studies performed with chlorothiazide doses of 50 mg/kg/day in rabbits, 60 mg/kg/day in rats and 500 mg/kg/day in mice revealed no external abnormalities of the fetus or impairment of growth and survival of the fetus due to chlorothiazide, such studies did not include complete examinations for visceral and skeletal abnormalities. It is not known whether chlorothiazide can cause fetal harm when administered to a pregnant woman; however, thiazides cross the placental barrier and appear in cord blood. Chlorothiazide should be used during pregnancy only if clearly needed (see ).
Chlorothiazide may cause fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions which have occurred in the adult.
Nursing Mothers
Because of the potential for serious adverse reactions in nursing infants from Chlorothiazide, 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
There are no well-controlled clinical trials in pediatric patients. Information on dosing in this age group is supported by evidence from empiric use in pediatric patients and published literature regarding the treatment of hypertension in such patients. (See .)
Geriatric Use
Clinical studies of chlorothiazide 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 of 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 ).
What are the side effects of Chlorothiazide?
The following adverse reactions have been reported and, within each category, are listed in order of decreasing severity.
Body as a whole:
Cardiovascular:
Digestive:
Hematologic:
Hypersensitivity:
Metabolic:
Musculoskeletal:
Nervous System/Psychiatric:
Renal:
Skin:
Special Senses:
Urogenital:
Whenever adverse reactions are moderate or severe, thiazide dosage should be reduced or therapy withdrawn.
What should I look out for while using Chlorothiazide?
Anuria.
Hypersensitivity to this product or to other sulfonamide-derived drugs.
Use with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.
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.
Thiazides may add to or potentiate the action of other antihypertensive drugs.
Sensitivity reactions 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.
Lithium generally should not be given with diuretics (see ).
What might happen if I take too much Chlorothiazide?
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.
In the event of overdosage, symptomatic and supportive measures should be employed. Emesis should be induced or gastric lavage performed. Correct dehydration, electrolyte imbalance, hepatic coma and hypotension by established procedures. If required, give oxygen or artificial respiration for respiratory impairment.
The degree to which chlorothiazide sodium is removed by hemodialysis has not been established.
The oral LD of chlorothiazide is 8.5 g/kg, greater than 10 g/kg, and greater than 1 g/kg, in the mouse, rat and dog respectively.
How should I store and handle Chlorothiazide?
Store at controlled room temperature 20° to 25°C (68° to 77°F) [see USP] .Chlorothiazide Tablets USP 250 mg: White, round, scored, compressed tablets imprinted "West-ward 209".Bottles of 100 tablets.Bottles of 1000 tablets.Chlorothiazide Tablets USP 500 mg: White, round, scored, compressed tablets imprinted "West-ward 210".Bottles of 100 tablets.Bottles of 1000 tablets.Store at 20-25°C (68-77°F) [See USP Controlled Room Temperature]. Protect from light and moisture.Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.Chlorothiazide Tablets USP 250 mg: White, round, scored, compressed tablets imprinted "West-ward 209".Bottles of 100 tablets.Bottles of 1000 tablets.Chlorothiazide Tablets USP 500 mg: White, round, scored, compressed tablets imprinted "West-ward 210".Bottles of 100 tablets.Bottles of 1000 tablets.Store at 20-25°C (68-77°F) [See USP Controlled Room Temperature]. Protect from light and moisture.Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.Chlorothiazide Tablets USP 250 mg: White, round, scored, compressed tablets imprinted "West-ward 209".Bottles of 100 tablets.Bottles of 1000 tablets.Chlorothiazide Tablets USP 500 mg: White, round, scored, compressed tablets imprinted "West-ward 210".Bottles of 100 tablets.Bottles of 1000 tablets.Store at 20-25°C (68-77°F) [See USP Controlled Room Temperature]. Protect from light and moisture.Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.Chlorothiazide Tablets USP 250 mg: White, round, scored, compressed tablets imprinted "West-ward 209".Bottles of 100 tablets.Bottles of 1000 tablets.Chlorothiazide Tablets USP 500 mg: White, round, scored, compressed tablets imprinted "West-ward 210".Bottles of 100 tablets.Bottles of 1000 tablets.Store at 20-25°C (68-77°F) [See USP Controlled Room Temperature]. Protect from light and moisture.Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.Chlorothiazide Tablets USP 250 mg: White, round, scored, compressed tablets imprinted "West-ward 209".Bottles of 100 tablets.Bottles of 1000 tablets.Chlorothiazide Tablets USP 500 mg: White, round, scored, compressed tablets imprinted "West-ward 210".Bottles of 100 tablets.Bottles of 1000 tablets.Store at 20-25°C (68-77°F) [See USP Controlled Room Temperature]. Protect from light and moisture.Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.Chlorothiazide Tablets USP 250 mg: White, round, scored, compressed tablets imprinted "West-ward 209".Bottles of 100 tablets.Bottles of 1000 tablets.Chlorothiazide Tablets USP 500 mg: White, round, scored, compressed tablets imprinted "West-ward 210".Bottles of 100 tablets.Bottles of 1000 tablets.Store at 20-25°C (68-77°F) [See USP Controlled Room Temperature]. Protect from light and moisture.Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.Chlorothiazide Tablets USP 250 mg: White, round, scored, compressed tablets imprinted "West-ward 209".Bottles of 100 tablets.Bottles of 1000 tablets.Chlorothiazide Tablets USP 500 mg: White, round, scored, compressed tablets imprinted "West-ward 210".Bottles of 100 tablets.Bottles of 1000 tablets.Store at 20-25°C (68-77°F) [See USP Controlled Room Temperature]. Protect from light and moisture.Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.Chlorothiazide Tablets USP 250 mg: White, round, scored, compressed tablets imprinted "West-ward 209".Bottles of 100 tablets.Bottles of 1000 tablets.Chlorothiazide Tablets USP 500 mg: White, round, scored, compressed tablets imprinted "West-ward 210".Bottles of 100 tablets.Bottles of 1000 tablets.Store at 20-25°C (68-77°F) [See USP Controlled Room Temperature]. Protect from light and moisture.Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
Clinical Information
Chemical Structure
No Image foundClinical Pharmacology
The mechanism of the antihypertensive effect of thiazides is unknown. Chlorothiazide does not usually effect normal blood pressure.
Chlorothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosage all thiazides are approximately equal in their diuretic efficacy.
Chlorothiazide 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 2 hours, peaks in about 4 hours, and lasts about 6 to 12 hours.
Non-Clinical Toxicology
Anuria.Hypersensitivity to this product or to other sulfonamide-derived drugs.
Use with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.
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.
Thiazides may add to or potentiate the action of other antihypertensive drugs.
Sensitivity reactions 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.
Lithium generally should not be given with diuretics (see ).
When given concurrently the following drugs may interact with thiazide diuretics.
Alcohol, barbiturates, or narcotics -
Antidiabetic drugs (oral agents and insulin) -
Other antihypertensive drugs -
Cholestyramine and colestipol resins -
Corticosteroids, ACTH -
Pressor amines (e.g., norepinephrine) -
Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine) -
Lithium -
Non-steroidal Anti-inflammatory Drugs -
All patients receiving diuretic therapy should be observed for evidence of fluid or electrolyte imbalance: namely, 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.
Hypokalemia may develop, especially with brisk diuresis, when severe cirrhosis is present or after prolonged therapy.
Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Hypokalemia may cause cardiac arrhythmias and may also sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability). Hypokalemia may be avoided or treated by use of potassium sparing diuretics or potassium supplements such as foods with a high potassium content.
Although any chloride deficit is generally mild and usually does not require specific treatment except under extraordinary circumstances (as in liver disease or renal disease), chloride replacement may be required in the treatment of metabolic alkalosis.
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.
Hyperuricemia may occur or acute gout may be precipitated in certain patients receiving thiazides.
In diabetic patients dosage adjustments of insulin or oral hypoglycemic agents may be required. Hyperglycemia may occur with thiazide diuretics. Thus latent diabetes mellitus may become manifest during thiazide therapy.
The antihypertensive effects of the drug may be enhanced in the post-sympathectomy patient.
If progressive renal impairment becomes evident, consider withholding or discontinuing diuretic therapy.
Thiazides have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia.
Thiazides 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 tests for parathyroid function.
Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy.
The following adverse reactions have been reported and, within each category, are listed in order of decreasing severity.
Body as a whole:
Cardiovascular:
Digestive:
Hematologic:
Hypersensitivity:
Metabolic:
Musculoskeletal:
Nervous System/Psychiatric:
Renal:
Skin:
Special Senses:
Urogenital:
Whenever adverse reactions are moderate or severe, thiazide dosage should be reduced or therapy withdrawn.
Reference
This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"
While we update our database periodically, we cannot guarantee it is always updated to the latest version.
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