Usage in Pregnancy
The routine use of diuretics in an otherwise healthy woman is
inappropriate 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 developed toxemia. Edema
during pregnancy may arise from pathologic causes or from the physiologic and
mechanical consequences of pregnancy. Chlorthalidone is indicated in pregnancy
when edema is due to pathologic causes, just as it is in the absence of
pregnancy (however, see PRECAUTIONS, below). Dependent
edema in pregnancy, resulting from restriction of venous return by the expanded
uterus, is properly treated through elevation of the lower extremities and use
of support hose; use of diuretics to lower intravascular volume in this case is
illogical and unnecessary. There is hypervolemia during normal pregnancy that is
harmful to neither the fetus nor the mother (in the absence of cardiovascular
disease), but that is associated with edema, including generalized edema, in the
majority of pregnant women. If this edema produces discomfort, increased
recumbency will often provide relief. In rare instances, this edema may cause
extreme discomfort that is not relieved by rest. In these cases, a short course
of diuretics may provide relief and be appropriate.
Chlorthalidone should be used with caution in severe renal
disease. In patients with renal disease, chlorthalidone or related drugs may
precipitate azotemia. Cumulative effects of the drug may develop in patients
with impaired renal function.
Chlorthalidone 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.
Sensitivity reactions may occur in patients with a history of allergy or
bronchial asthma.
The possibility of exacerbation or activation of systemic lupus erythematosus
has been reported with thiazide diuretics, which are structurally related to
chlorthalidone. However, systemic lupus erythematosus has not been reported
following chlorthalidone administration.
Hypokalemia may develop with chlorthalidone as with any other
diuretic, especially with brisk diuresis when severe cirrhosis is present or
during concomitant use of corticosteroids or ACTH.
Interference with adequate oral electrolyte intake will also contribute to
hypokalemia. 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
actual salt depletion, appropriate replacement is the therapy of choice.
Hyperuricemia may occur or frank gout may be precipitated in certain patients
receiving chlorthalidone. Thiazide-like diuretics have been shown to increase
the urinary excretion of magnesium; this may result in hypomagnesemia.
The antihypertensive effects of the drug may be enhanced in the
post-sympathectomy patient.
If progressive renal impairment becomes evident, as indicated by a rising
nonprotein nitrogen or blood urea nitrogen, a careful reappraisal of therapy is
necessary with consideration given to withholding or discontinuing diuretic
therapy.
Calcium excretion is decreased by thiazide-like drugs. Pathological changes
in the parathyroid gland with hypercalcemia and hypophosphatemia have been
observed in few patients on thiazide therapy. The common complications of
hyperparathyroidism such as renal lithiasis, bone resorption and peptic
ulceration have not been seen.
Laboratory Tests
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.
Pregnancy
Teratogenic Effects. 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.
Nonteratogenic Effects
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.
Nursing Mothers
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.
Pediatric Use
Safety and effectiveness in children have not been established.
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