Usual Adult Dose for Edema

Oral or IV: 500 to 1000 mg once or twice a day.

Usual Adult Dose for Hypertension

Oral or IV: 500 to 1000 mg once or twice a day.

Usual Pediatric Dose for Edema

Note: IV use of chlorothiazide in infants and children has not been well established. If IV therapy is required, the lowest dosage should be used to achieve the desired response. Once the patient is able to take oral medications, chlorothiazide oral may be substituted for IV therapy, using the same dosage schedule as for the parenteral route. Due to the variable and often poor oral bioavailability of chlorothiazide, particularly at higher dosages, patient response should be closely monitored and the dosage adjusted accordingly.

Infants less than 6 months:
Oral: 10 to 30 mg/kg/day in 2 divided doses
Maximum dose: 375 mg/day orally
Anecdotal reports have used up to 40 mg/kg/day (unlabeled).
IV (unlabeled): 2 to 8 mg/kg/day in 2 divided doses
Anecdotal reports have used up to 20 mg/kg/day
Infants greater than 6 months and Children:
Oral: 10 to 20 mg/kg/day in 1 to 2 divided doses
Maximum dose: 375 mg/day orally in children less than 2 years or 1 g/day orally in children 2 to 12 years
IV (unlabeled route): 4 mg/kg/day in 1 to 2 divided doses
Anecdotal reports have used up to 20 mg/kg/day

Usual Pediatric Dose for Hypertension

Note: IV use of chlorothiazide in infants and children has not been well established. If IV therapy is required, the lowest dosage should be used to achieve the desired response. Once the patient is able to take oral medications, chlorothiazide oral may be substituted for IV therapy, using the same dosage schedule as for the parenteral route. Due to the variable and often poor oral bioavailability of chlorothiazide, particularly at higher dosages, patient response should be closely monitored and the dosage adjusted accordingly.

Infants less than 6 months:
Oral: 10 to 30 mg/kg/day in 2 divided doses
Maximum dose: 375 mg/day orally
Anecdotal reports have used up to 40 mg/kg/day (unlabeled).
IV (unlabeled): 2 to 8 mg/kg/day in 2 divided doses
Anecdotal reports have used up to 20 mg/kg/day
Infants greater than 6 months and Children:
Oral: 10 to 20 mg/kg/day in 1 to 2 divided doses
Maximum dose: 375 mg/day orally in children less than 2 years or 1 g/day orally in children 2 to 12 years
IV (unlabeled route): 4 mg/kg/day in 1 to 2 divided doses
Anecdotal reports have used up to 20 mg/kg/day

Renal Dose Adjustments

Chlorothiazide is not recommended in patients with severe renal insufficiency since it is not expected to be filtered into the renal tubule (its site of action) when the glomerular filtration rate is less than 25 mL/min.

Liver Dose Adjustments

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.

Dose Adjustments

Many patients with edema respond to intermittent therapy by giving doses on alternate days or 3 to 5 days/week.

Precautions

Chlorothiazide is contraindicated in patients with anuria. Like other diuretics, chlorothiazide, should be used with caution in patients with severe liver disease. The possible electrolyte and intravascular fluid shifts associated with chlorothiazide-induced diuresis has resulted in hepatic coma and death in some patients with hepatic cirrhosis and ascites.

Chlorothiazide should be used with caution in patients with severe renal disease. In individuals with renal disease, thiazides may precipitate azotemia. Cumulative effects of chlorothiazide may develop in patients with impaired renal function. If progressive renal impairment becomes evident, withholding or discontinuing diuretic therapy should be considered.

Thiazides should be used with caution in individuals with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

Sensitivity reactions may be observed in patients with or without a history of allergy or bronchial asthma.

Exacerbation or activation of systemic lupus erythematosus has been reported.

All patients receiving diuretic treatment 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 individual 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 treatment.

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 necessary in the treatment of metabolic alkalosis.

Dilutional hyponatremia may occur in edematous individual 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 treatment of choice.

Hyperuricemia may occur or acute gout may be precipitated in certain individuals receiving thiazides.

In diabetic patients, dosage adjustments of insulin or oral hypoglycemic agents may be required. Hyperglycemia may be observed with thiazide diuretics. Thus latent diabetes mellitus may become manifest during thiazide treatment.

Thiazides have been shown to increase the urinary excretion of magnesium, which 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 treatment.

Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be conducted at appropriate intervals.

Dialysis

Data regarding the disposition of chlorothiazide in patients undergoing hemodialysis is not available. Chlorothiazide is not efficacious in patients with end-stage renal disease as it is not secreted into the renal tubule (its site of action) in renal patients with failure.

Other Comments

Daily doses above 1 g twice a day are rarely required.

Periodic monitoring of electrolytes is recommended, particularly in elderly patients and in patients receiving a high dose.

Frequently asked questions

• Should you use a diuretic with diazoxide?