Nadolol should be used with caution in patients with impaired renal function (see DOSAGE AND ADMINISTRATION).
Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be
performed at appropriate intervals.
All patients receiving thiazide therapy 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. Warning signs or symptoms of fluid and electrolyte imbalance may include:
dryness of the mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps,
muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances, such as nausea
Hypokalemia may develop, especially with brisk diuresis or when severe cirrhosis is present.
Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Hypokalemia can
sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased
ventricular irritability). Concurrent administration of a potassium-sparing diuretic or potassium
supplements may be indicated in these patients.
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 thiazide
Latent diabetes mellitus may become manifest during thiazide administration.
The antihypertensive effect of thiazide diuretics may be enhanced in the postsympathectomy patient.
If progressive renal impairment becomes evident, as indicated by a rising nonprotein nitrogen or blood
urea nitrogen (BUN), a careful reappraisal of therapy is necessary with consideration given to
withholding or discontinuing diuretic therapy.
Thiazides may decrease serum PBI levels without signs of thyroid disturbance.
Calcium excretion is decreased by thiazides. Pathological changes in the parathyroid gland with
hypercalcemia and hypophosphatemia have been observed in a few patients on prolonged thiazide
therapy. The common complications of hyperparathyroidism such as renal lithiasis, bone resorption, and
peptic ulceration have not been seen. Thiazides should be discontinued before carrying out tests for
Thiazides have been shown to increase the urinary excretion of magnesium; this may result in
Serum electrolyte levels should be regularly monitored (see WARNINGS, Bendroflumethiazide, also
PRECAUTIONS, General, Bendroflumethiazide).
Carcinogenesis, Mutagenesis, Impairment Of Fertility
In chronic oral toxicologic studies (one to two years) in mice, rats, and dogs, nadolol did not produce
any significant toxic effects. In two-year oral carcinogenicity studies in rats and mice, nadolol did not
produce any neoplastic, preneoplastic, or nonneoplastic pathologic lesions. In fertility and general
reproductive performance studies in rats, nadolol caused no adverse effect.
Studies have not been performed to evaluate carcinogenic potential, mutagenesis, or whether this drug
adversely affects fertility in males or females.
Pregnancy - Teratogenic Effects
In animal reproduction studies with nadolol, evidence of embryo-and fetotoxicity was found in rabbits,
but not in rats or hamsters, at doses 5 to 10 times greater (on a mg/kg basis) than the maximum indicated
human dose. No teratogenic potential was observed in any of these species.
There are no adequate and well-controlled studies in pregnant women. Nadolol should be used during
pregnancy only if the potential benefit justifies the potential risk to the fetus. Neonates whose mothers
are receiving nadolol at parturition have exhibited bradycardia, hypoglycemia, and associated
Animal reproduction studies have not been conducted with bendroflumethiazide. It is also not known
whether this drug can cause fetal harm when administered to a pregnant woman or can affect
reproduction capacity. Bendroflumethiazide should be given to a pregnant woman only if clearly
Pregnancy - Nonteratogenic Effects
Thiazides cross the placental barrier and appear in cord blood. The use of thiazides in pregnant women
requires that the anticipated benefit be weighed against possible hazards to the fetus. These hazards
include fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions which have
occurred in the adult.
Both nadolol and bendroflumethiazide are excreted in human milk. Because of the potential for serious
adverse reactions in nursing infants from both drugs, a decision should be made whether to discontinue
nursing or to discontinue therapy taking into account the importance of CORZIDE (Nadolol and
Bendroflumethiazide Tablets) to the mother.
Safety and effectiveness in pediatric patients have not been established.
Clinical studies of Corzide 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
reaction to this drug may be greater in patients with impaired 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.