Hypokalemia and other electrolyte abnormalities, including hyponatremia and
hypochloremic alkalosis, are common in patients receiving chlorthalidone. These
abnormalities are dose-related but may occur even at the lowest marketed doses
of chlorthalidone. Serum electrolytes should be determined before initiating
therapy and at periodic intervals during therapy.Serum and urine electrolyte
determinations are particularly important when the patient is vomiting excessively
or receiving parenteral fluids. All patients taking chlorthalidone should be
observed for clinical signs of electrolyte imbalance, including dryness of mouth,
thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps,
muscular fatigue, hypotension, oliguria, tachycardia, palpitations and gastrointestinal
disturbances, such as nausea and vomiting. Digitalis therapy may exaggerate
metabolic effects of hypokalemia especially with reference to myocardial activity.
Any chloride deficit is generally mild and 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 cases
of actual salt depletion, appropriate replacement is the therapy of choice.
Thiazide-like diuretics have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia.
Calcium excretion is decreased by thiazide-like drugs. Pathological changes
in the parathyroid gland with hypercalcemia and hypophos-phatemia have been
observed in a few patients on thiazide therapy. The common complications of
hyperparathyroidism such as renal lithiasis, bone resorption and peptic ulceration
have not been seen.
Hyperuricemia may occur or frank gout may be precipitated in certain patients
Increases in serum glucose may occur and latent diabetes melli-tus may become
manifest during chlorthalidone therapy (see PRECAUTIONS: DRUG
INTERACTIONS). Chlorthalidone and related drugs may decrease serum PBI
levels without signs of thyroid disturbance.
Periodic determination of serum electrolytes to detect possible electrolyte
imbalance should be performed at appropriate intervals.
All patients receiving chlorthalidone should be observed for clinical signs 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.
Carcinogenesis, Mutagenesis, Impairment of Fertility
No information is available.
PREGNANCY CATEGORY B: Reproduction studies have been performed in the rat
and the rabbit at doses up to 420 times the human dose and have revealed no
evidence of harm to the fetus due to chlorthalidone. There are, however, no
adequate and well-controlled studies in pregnant women. Because animal reproduction
studies are not always predictive of human response, this drug should be used
during pregnancy only if clearly needed.
Thiazides cross the placental barrier and appear in cord blood.The use of
chlorthalidone and related drugs in pregnant women requires that the anticipated
benefits of the drug be weighed against possible hazards to the fetus.These
hazards include fetal or neonatal jaundice,thrombocytopenia,and possibly other
adverse reactions that have occurred in the adult.
Thiazides are excreted in human milk.Because of the potential for serious adverse
reactions in nursing infants from chlorthalidone,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.
Safety and effectiveness in children have not been established.
Clinical studies of Thalitone® (chlorthalidone) 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.