WARNINGS
Cardiac Failure
Sympathetic stimulation may be a vital component supporting
circulatory function in patients with congestive heart
failure, and its inhibition by beta-blockade may precipitate
more severe failure. Although beta-blockers should be
avoided in overt congestive heart failure, if necessary,
they can be used with caution in patients with a history
of failure who are well-compensated, usually with digitalis
and diuretics. Beta-adrenergic blocking agents do not
abolish the inotropic action of digitalis on heart muscle.
IN PATIENTS WITHOUT A HISTORY OF HEART FAILURE, continued
use of beta-blockers can, in some cases, lead to cardiac
failure. Therefore, at the first sign or symptom of heart
failure, the patient should be digitalized and/or treated
with diuretics, and the response observed closely, or nadolol
should be discontinued (gradually, if possible).
| Exacerbation
of Ischemic Heart Disease Following Abrupt Withdrawal
Hypersensitivity to catecholamines
has been observed in patients withdrawn from beta-blocker
therapy; exacerbation of angina and, in some cases,
myocardial infarction have occurred after abrupt
discontinuation of such therapy. When discontinuing
chronically administered nadolol, particularly in
patients with ischemic heart disease, the dosage
should be gradually reduced over a period of one
to two weeks and the patient should be carefully
monitored. If angina markedly worsens or acute coronary
insufficiency develops, nadolol administration should
be reinstituted promptly, at least temporarily,
and other measures appropriate for the management
of unstable angina should be taken. Patients should
be warned against interruption or discontinuation
of therapy without the physician's advice. Because
coronary artery disease is common and may be unrecognized,
it may be prudent not to discontinue nadolol therapy
abruptly even in patients treated only for hypertension.
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Nonallergic Bronchospasm (e.g., chronic
bronchitis, emphysema)
PATIENTS WITH BRONCHOSPASTIC DISEASES SHOULD IN GENERAL
NOT RECEIVE BETA-BLOCKERS. Nadolol should be administered
with caution since it may block bronchodilation produced
by endogenous or exogenous catecholamine stimulation of
beta2 receptors.
Major Surgery
Because beta-blockade impairs the ability of the heart
to respond to reflex stimuli and may increase the risks
of general anesthesia and surgical procedures, resulting
in protracted hypotension or low cardiac output, it has
generally been suggested that such therapy should be withdrawn
several days prior to surgery. Recognition of the increased
sensitivity to catecholamines of patients recently withdrawn
from beta-blocker therapy, however, has made this recommendation
controversial. If possible, beta-blockers should be withdrawn
well before surgery takes place. In the event of emergency
surgery, the anesthesiologist should be informed that
the patient is on beta-blocker therapy. The effects of
nadolol can be reversed by administration of beta-receptor
agonists such as isoproterenol, dopamine, dobutamine,
or levarterenol. Difficulty in restarting and maintaining
the heart beat has also been reported with beta-adrenergic
receptor blocking agents.
Diabetes and Hypoglycemia
Beta-adrenergic blockade may prevent the appearance of
premonitory signs and symptoms (e.g., tachycardia and
blood pressure changes) of acute hypoglycemia. This is
especially important with labile diabetics. Beta-blockade
also reduces the release of insulin in response to hyperglycemia;
therefore, it may be necessary to adjust the dose of antidiabetic
drugs.
Thyrotoxicosis
Beta-adrenergic blockade may mask certain clinical signs
(e.g., tachycardia) of hyperthyroidism. Patients suspected
of developing thyrotoxicosis should be managed carefully
to avoid abrupt withdrawal of beta-adrenergic blockade
which might precipitate a thyroid storm.
PRECAUTIONS
Impaired Renal Function
Nadolol should be used with caution in patients with
impaired renal function (see DOSAGE AND ADMINISTRATION).
Information for Patients
See PATIENT INFORMATION section.
Drug Interactions
See DRUG INTERACTIONS section.
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 carcinogenic 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 effects.
Pregnancy Category C
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 symptoms.
Nursing Mothers
Nadolol is excreted in human milk. Because of the potential
for adverse effects in nursing infants, a decision should
be made whether to discontinue nursing or to discontinue
therapy taking into account the importance of nadolol
to the mother.
Pediatric Use
Safety and effectiveness in children have not been established.
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