CONTRAINDICATIONS
Digitalis glycosides are contraindicated in patients with ventricular fibrillation or in patients with a
known hypersensitivity to digoxin. A hypersensitivity reaction to other digitalis preparations usually
constitutes a contraindication to digoxin.
WARNINGS
Sinus Node Disease and AV Block: Because digoxin slows sinoatrial and AV conduction, the
drug commonly prolongs the PR interval. The drug may cause severe sinus bradycardia or sinoatrial
block in patients with pre-existing sinus node disease and may cause advanced or complete heart
block in patients with pre-existing incomplete AV block. In such patients consideration should be
given to the insertion of a pacemaker before treatment with digoxin.
Accessory AV Pathway (Wolff-Parkinson-White Syndrome): After intravenous digoxin therapy,
some patients with paroxysmal atrial fibrillation or flutter and a coexisting accessory AV pathway
have developed increased antegrade conduction across the accessory pathway bypassing the AV
node, leading to a very rapid ventricular response or ventricular fibrillation. Unless conduction down
the accessory pathway has been blocked (either pharmacologically or by surgery), digoxin should
not be used in such patients. The treatment of paroxysmal supraventricular tachycardia in such
patients is usually direct-current cardioversion.
Use in Patients with Preserved Left Ventricular Systolic Function: Patients with certain
disorders involving heart failure associated with preserved left ventricular ejection fraction may be
particularly susceptible to toxicity of the drug. Such disorders include restrictive cardiomyopathy,
constrictive pericarditis, amyloid heart disease, and acute cor pulmonale. Patients with idiopathic
hypertrophic subaortic stenosis may have worsening of the outflow obstruction due to the inotropic
effects of digoxin.
PRECAUTIONS
Use in Patients with Impaired Renal Function: Digoxin is primarily excreted by the kidneys;
therefore, patients with impaired renal function require smaller than usual maintenance doses of
digoxin (see DOSAGE AND ADMINISTRATION). Because of the prolonged elimination
half-life, a longer period of time is required to achieve an initial or new steady-state serum
concentration in patients with renal impairment than in patients with normal renal function. If
appropriate care is not taken to reduce the dose of digoxin, such patients are at high risk for toxicity,
and toxic effects will last longer in such patients than in patients with normal renal function.
Use in Patients with Electrolyte Disorders: In patients with hypokalemia or hypomagnesemia,
toxicity may occur despite serum digoxin concentrations below 2.0 ng/ml, because potassium or
magnesium depletion sensitizes the myocardium to digoxin. Therefore, it is desirable to maintain
normal serum potassium and magnesium concentrations in patients being treated with digoxin.
Deficiencies of these electrolytes may result from malnutrition, diarrhea, or prolonged vomiting, as
well as the use of the following drugs or procedures: diuretics, amphotericin B, corticosteroids,
antacids, dialysis, and mechanical suction of gastrointestinal secretions.
Hypercalcemia from any cause predisposes the patient to digitalis toxicity. Calcium, particularly
when administered rapidly by the intravenous route, may produce serious arrhythmias in digitalized
patients. On the other hand, hypocalcemia can nullify the effects of digoxin in humans; thus, digoxin
may be ineffective until serum calcium is restored to normal. These interactions are related to the
fact that digoxin affects contractility and excitability of the heart in a manner similar to that of
calcium.
Use in Thyroid Disorders and Hypermetabolic States: Hypothyroidism may reduce the
requirements for digoxin. Heart failure and/or atrial arrhythmias resulting from hypermetabolic or
hyperdynamic states (e.g., hyperthyroidism, hypoxia, or arteriovenous shunt) are best treated by
addressing the underlying condition. Atrial arrhythmias associated with hypermetabolic states are
particularly resistant to digoxin treatment. Care must be taken to avoid toxicity if digoxin is used.
Use in Patients with Acute Myocardial Infarction: Digoxin should be used with caution in
patients with acute myocardial infarction. The use of inotropic drugs in some patients in this setting
may result in undesirable increases in myocardial oxygen demand and ischemia.
Use During Electrical Cardioversion: It may be desirable to reduce the dose of digoxin for 1 to 2
days prior to electrical cardioversion of atrial fibrillation to avoid the induction of ventricular
arrhythmias, but physicians must consider the consequences of increasing the ventricular response
if digoxin is withdrawn. If digitalis toxicity is suspected, elective cardioversion should be delayed. If
it is not prudent to delay cardioversion, the lowest possible energy level should be selected to avoid
provoking ventricular arrhythmias.
Laboratory Test Monitoring: Patients receiving digoxin should have their serum electrolytes and
renal function (serum creatinine concentrations) assessed periodically; the frequency of
assessments will depend on the clinical setting. For discussion of serum digoxin concentrations, see
DOSAGE AND ADMINISTRATION.
Drug/Laboratory Test Interactions: The use of therapeutic doses of digoxin may cause
prolongation of the PR interval and depression of the ST segment on the electrocardiogram. Digoxin
may produce false positive ST-T changes on the electrocardiogram during exercise testing. These
electrophysiologic effects reflect an expected effect of the drug and are not indicative of toxicity.
Carcinogenesis, Mutagenesis, and Impairment of Fertility: There have been no long-term
studies performed in animals to evaluate carcinogenic potential, nor have studies been conducted to
assess the mutagenic potential of digoxin or its potential to affect fertility.
Pregnancy, Teratogenic Effects, Pregnancy Category C: Animal reproduction studies have not
been conducted with digoxin. It is also not known whether digoxin can cause fetal harm when
administered to a pregnant woman or can affect reproductive capacity. Digoxin should be given to a
pregnant woman only if clearly needed.
Nursing Mothers: Studies have shown that digoxin concentrations in the mother's serum and milk
are similar. However, the estimated exposure of a nursing infant to digoxin via breast feeding will
be far below the usual infant maintenance dose. Therefore, this amount should have no
pharmacologic effect upon the infant. Nevertheless, caution should be exercised when digoxin is
administered to a nursing woman.
Pediatric Use: Newborn infants display considerable variability in their tolerance to digoxin.
Premature and immature infants are particularly sensitive to the effects of digoxin, and the dosage
of the drug must not only be reduced but must be individualized according to their degree of
maturity. Digitalis glycosides can cause poisoning in children due to accidental ingestion.
Geriatric Use: The majority of clinical experience gained with digoxin has been in the elderly
population. This experience has not identified differences in response or adverse effects between
the elderly and younger patients. However, 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, which should be based on renal function, and it may be useful to monitor
renal function (see DOSAGE AND ADMINISTRATION).