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.
Periodic determination of serum electrolytes to detect
possible electrolyte imbalance should be done at appropriate intervals.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity studies have not been conducted with
Chlorothiazide was not mutagenic in vitro in the Ames
microbial mutagen test (using a maximum concentration of 5 mg/plate and
Salmonella typhimurium strains TA98 and TA100) and was not mutagenic and did
not induce mitotic nondisjunction in diploid-strains of Aspergillus nidulans.
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 times** the
recommended maximum human dose, respectively, when compared on a body weight
Pregnancy Category C: 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. DIURIL (chlorothiazide) should be used during pregnancy only if clearly needed
(see INDICATIONS AND USAGE).
Chlorothiazide may cause fetal or neonatal jaundice,
thrombocytopenia, and possibly other adverse reactions which have occurred in
Because of the potential for serious adverse reactions in
nursing infants from DIURIL (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.
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 DOSAGE AND ADMINISTRATION,
Infants and Children.)
Clinical studies of DIURIL (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 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 WARNINGS).
** Calculations based on a human body weight of 50 kg