Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/2233
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LANOXICAPS (Capsule, Liquid Filled)
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dailymed-instance:dosage |
General: Recommended dosages of digoxin may require considerable
modification because of individual sensitivity of the patient to the drug,
the presence of associated conditions, or the use of concurrent medications.
Due to the more complete absorption of digoxin from soft capsules, recommended
oral doses are only 80 percent of those for Tablets and Elixir. Because
the significance of the higher peak serum concentrations associated with once
daily capsules is not established, divided daily dosing is presently recommended
for: Where compliance is considered a problem, single daily
dosing may be appropriate. In selecting a dose of digoxin,
the following factors must be considered:<br/>Serum Digoxin Concentrations: In general, the dose of digoxin used should be determined
on clinical grounds. However, measurement of serum digoxin concentrations
can be helpful to the clinician in determining the adequacy of digoxin therapy
and in assigning certain probabilities to the likelihood of digoxin intoxication.
About two thirds of adults considered adequately digitalized (without evidence
of toxicity) have serum digoxin concentrations ranging from 0.8 to 2.0 ng/mL.
However, digoxin may produce clinical benefits even at serum concentrations
below this range. About two thirds of adult patients with clinical toxicity
have serum digoxin concentrations greater than 2.0 ng/mL. However, since
one third of patients with clinical toxicity have concentrations less than
2.0 ng/mL, values below 2.0 ng/mL do not rule out the possibility
that a certain sign or symptom is related to digoxin therapy. Rarely, there
are patients who are unable to tolerate digoxin at serum concentrations below
0.8 ng/mL. Consequently, the serum concentration of digoxin should always
be interpreted in the overall clinical context, and an isolated measurement
should not be used alone as the basis for increasing or decreasing the dose
of the drug. To allow adequate time for equilibration
of digoxin between serum and tissue, sampling of serum concentrations should
be done just before the next scheduled dose of the drug. If this is not possible,
sampling should be done at least 6 to 8 hours after the last dose, regardless
of the route of administration or the formulation used. On a once-daily dosing
schedule, the concentration of digoxin will be 10% to 25% lower when sampled
at 24 versus 8 hours, depending upon the patient's renal
function. On a twice-daily dosing schedule, there will be only minor differences
in serum digoxin concentrations whether sampling is done at 8 or 12 hours
after a dose. If a discrepancy exists between the reported
serum concentration and the observed clinical response, the clinician should
consider the following possibilities:<br/>Heart Failure:<br/>Adults: Digitalization may be accomplished by either of two general
approaches that vary in dosage and frequency of administration, but reach
the same endpoint in terms of total amount of digoxin accumulated in the body.<br/>Infants and Children: In general, divided daily dosing is recommended for infants
and young children (under age 10). In these patients, where dosage adjustment
is frequent and outside the fixed dosages available, LANOXICAPS may not be
the formulation of choice. In the newborn period, renal clearance of digoxin
is diminished and suitable dosage adjustments must be observed. This is especially
pronounced in the premature infant. Beyond the immediate newborn period, children
generally require proportionally larger doses than adults on the basis of
body weight or body surface area. Children over 10 years of age require
adult dosages in proportion to their body weight. Some researchers have suggested
that infants and young children tolerate slightly higher serum concentrations
than do adults. Daily maintenance doses for each age
group are given in Table 6 and should provide therapeutic effects with
minimum risk of toxicity in most patients with heart failure and normal sinus
rhythm. These recommendations assume the presence of normal renal function: IV digitalizing doses
are the same as digitalizing doses of LANOXICAPS. Divided
daily dosing is recommended for children under 10 years of age. Projected or actual digitalizing dose
providing desired clinical response. In children with
renal disease, digoxin must be carefully titrated based upon clinical response. It cannot be overemphasized that both the adult and pediatric
dosage guidelines provided are based upon average patient response and substantial
individual variation can be expected. Accordingly, ultimate dosage selection
must be based upon clinical assessment of the patient.<br/>Atrial Fibrillation: Peak digoxin body stores larger than the 8 to 12 mcg/kg
required for most patients with heart failure and normal sinus rhythm have
been used for control of ventricular rate in patients with atrial fibrillation.
Doses of digoxin used for the treatment of chronic atrial fibrillation should
be titrated to the minimum dose that achieves the desired ventricular rate
control without causing undesirable side effects. Data are not available to
establish the appropriate resting or exercise target rates that should be
achieved.<br/>Dosage Adjustment When Changing Preparations: The absolute bioavailability of the capsule formulation
is greater than that of the standard tablets and very near that of the intravenous
dosage form. As a result, the doses recommended for LANOXICAPS Capsules are
the same as those for LANOXIN Injection (see Table 1 in CLINICAL PHARMACOLOGY:
Pharmacokinetics). Adjustments in dosage will seldom be necessary when converting
a patient from the intravenous formulation to LANOXICAPS. The difference in
bioavailability between LANOXIN Injection or LANOXICAPS and LANOXIN Elixir
Pediatric or LANOXIN Tablets must be considered when changing patients from
one dosage form to another. Doses of 100 mcg
(0.1 mg) and 200 mcg (0.2 mg) of LANOXICAPS are approximately
equivalent to 125-mcg (0.125-mg) and 250-mcg (0.25-mg) doses of LANOXIN Tablets
and Elixir Pediatric, respectively (see Table 1 in CLINICAL PHARMACOLOGY:
Pharmacokinetics).
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dailymed-instance:descripti... |
LANOXIN (digoxin) is one of the cardiac (or digitalis) glycosides,
a closely related group of drugs having in common specific effects on the
myocardium. These drugs are found in a number of plants. Digoxin is extracted
from the leaves of Digitalis lanata. The
term���digitalis���is used to designate the whole group of glycosides.
The glycosides are composed of two portions: a sugar and a cardenolide (hence���glycosides���). Digoxin is described chemically
as (3��,5��,12��)-3-[(O-2,6-dideoxy-��-D-ribo-hexopyranosyl-(1���4)-O-2,6-dideoxy-��-D-ribo-hexopyranosyl-(1���4)-2,6-dideoxy-��-D-ribo-hexopyranosyl)oxy]-12,14-dihydroxy-card-20(22)-enolide.
Its molecular formula is CHO, its molecular
weight is 780.95, and its structural formula is: Digoxin
exists as odorless white crystals that melt with decomposition above 230��C.
The drug is practically insoluble in water and in ether; slightly soluble
in diluted (50%) alcohol and in chloroform; and freely soluble in pyridine. LANOXICAPS
is a stable solution of digoxin enclosed within a soft gelatin capsule for
oral use. Each capsule contains the labeled amount of digoxin USP dissolved
in a solvent comprised of polyethylene glycol 400 USP, 8 percent ethyl alcohol,
propylene glycol USP, and purified water USP. Inactive ingredients in the
capsule shell include D&C Yellow No. 10 (0.1-mg and 0.2-mg Capsules),
FD&C Blue No. 1 (0.2-mg Capsule), gelatin, glycerin, methylparaben and
propylparaben (added as preservatives), purified water, and sorbitol. Capsules
are printed with edible ink.
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dailymed-instance:clinicalP... |
Mechanism of Action: Digoxin inhibits sodium-potassium ATPase, an enzyme that
regulates the quantity of sodium and potassium inside cells. Inhibition of
the enzyme leads to an increase in the intracellular concentration of sodium
and thus (by stimulation of sodium-calcium exchange) an increase in the intracellular
concentration of calcium. The beneficial effects of digoxin result from direct
actions on cardiac muscle, as well as indirect actions on the cardiovascular
system mediated by effects on the autonomic nervous system. The autonomic
effects include: (1) a vagomimetic action, which is responsible for the
effects of digoxin on the sinoatrial and atrioventricular(AV) nodes; and
(2) baroreceptor sensitization, which results in increased afferent inhibitory
activity and reduced activity of the sympathetic nervous system and renin-angiotensin
system for any given increment in mean arterial pressure. The pharmacologic
consequences of these direct and indirect effects are: (1) an increase
in the force and velocity of myocardial systolic contraction (positive inotropic
action); (2) a decrease in the degree of activation of the sympathetic
nervous system and renin-angiotensin system (neurohormonal deactivating effect);
and (3) slowing of the heart rate and decreased conduction velocity through
the AV node (vagomimetic effect). The effects of digoxin in heart failure
are mediated by its positive inotropic and neurohormonal deactivating effects,
whereas the effects of the drug in atrial arrhythmias are related to its vagomimetic
actions. In high doses, digoxin increases sympathetic outflow from the central
nervous system (CNS). This increase in sympathetic activity may be animportant
factor in digitalis toxicity.<br/>Pharmacokinetics:<br/>Absorption: Absorption of digoxin from LANOXICAPS Capsules has been
demonstrated to be 90% to 100% complete compared to an identical intravenous
dose of digoxin (absolute bioavailability). In comparison, the absolute bioavailability
of conventional digoxin tablets has been demonstrated to be 60% to 80%. The
enhanced absorption from LANOXICAPS compared to digoxin tablets and elixir
is associated with reduced between-patient and within-patient variability
in steady-state serum concentrations. The peak serum concentrations are higher
than those observed after tablets. Whendigoxin tablets or capsules are taken
after meals, the rate of absorption is slowed, but the total amount of digoxin
absorbed is usually unchanged. When taken with meals high in bran fiber, however,
the amount absorbed from an oral dose may be reduced. Comparisons of the systemic
availability and equivalent doses for preparations of LANOXIN are shown in
Table 1. For example, 125 mcg LANOXIN
Tablets equivalent to 125 mcg LANOXIN Elixir Pediatric equivalent to
100 mcg LANOXICAPS equivalent to 100 mcg LANOXIN Injection/IV. In
some patients, orally administered digoxin is converted to inactive reduction
products (e.g., dihydrodigoxin) by colonic bacteria in the gut. Data suggest
that 1 in 10 patients treated with digoxin tablets will degrade 40% or more
of the ingested dose. As a result, certain antibiotics may increase the absorption
of digoxin in such patients. Although inactivation of these bacteria by antibiotics
is rapid, the serum digoxin concentration will rise at a rate consistent with
the elimination half-life of digoxin. The magnitude of rise in serum digoxin
concentration relates to the extent of bacterial inactivation, and may be
as much as 2-fold in some cases. This phenomenon is minimized with LANOXICAPS
because they are rapidly absorbed in the upper gastrointestinal tract.<br/>Distribution: Following drug administration, a 6- to 8-hour tissue distribution
phase is observed. This is followed by a much more gradual decline in the
serum concentration of the drug, which is dependent on the elimination of
digoxin from the body. The peak height and slope of the early portion (absorption/distribution
phases) of the serum concentration-time curve are dependent upon the route
of administration and the absorption characteristics of the formulation. Clinical
evidence indicates that the early high serum concentrations (particularly
high for digoxin capsules) do not reflect the concentration of digoxin at
its site of action, but that with chronic use, the steady-state post-distribution
serum levels are in equilibrium with tissue concentrations and correlate with
pharmacologic effects. In individual patients, these post-distribution serum
concentrations may be useful in evaluating therapeutic and toxic effects (see
DOSAGE AND ADMINISTRATION: Serum Digoxin Concentrations). Digoxin
is concentrated in tissues and therefore has a large apparent volume of distribution.
Digoxin crosses both the blood-brain barrier and the placenta. At delivery,
the serum digoxin concentration in the newborn is similar to the serum concentration
in the mother. Approximately 25% of digoxin in the plasma is bound to protein.
Serum digoxin concentrations are not significantly altered by large changes
in fat tissue weight, so that its distribution space correlates best with
lean (i.e., ideal) body weight, not total body weight.<br/>Metabolism: Only a small percentage (16%) of a dose of digoxin is metabolized.
The end metabolites, which include 3��-digoxigenin, 3-keto-digoxigenin,
and their glucuronide and sulfate conjugates, are polar in nature and are
postulated to be formed via hydrolysis, oxidation, and conjugation. The metabolism
of digoxin is not dependent upon the cytochrome P-450 system, and digoxin
is not known to induce or inhibit the cytochrome P-450 system.<br/>Excretion: Elimination of digoxin follows first-order kinetics (that
is, the quantity of digoxin eliminated at any time is proportional to the
total body content). Following intravenous administration to healthy volunteers,
50% to 70% of a digoxin dose is excreted unchanged in the urine. Renal excretion
of digoxin is proportional to glomerular filtration rate and is largely independent
of urine flow. In healthy volunteers with normal renal function,digoxin has
a half-life of 1.5 to 2.0 days. The half-life in anuric patients is prolonged
to 3.5 to 5 days. Digoxin is not effectively removed from the body by
dialysis, exchange transfusion, or during cardiopulmonary bypass because most
of the drug is bound to tissue and does not circulate in the blood.<br/>Special Populations: Race differences in digoxin pharmacokinetics have not been
formally studied. Because digoxin is primarily eliminated as unchanged drug
via the kidney and because there are no important differences in creatinine
clearance among races, pharmacokinetic differences due to race are not expected. The
clearance of digoxin can be primarily correlated with renal function as indicated
by creatinine clearance. The Cockcroft and Gault formula for estimation of
creatinine clearance includes age, body weight, and gender. A table that provides
the usual daily maintenance dose requirements of LANOXICAPS Capsules based
on creatinine clearance (per 70 kg) is presented in the DOSAGE AND ADMINISTRATION
section. Plasma digoxin concentration profiles in patients
with acute hepatitis generally fell within the range of profiles in a group
of healthy subjects.<br/>Pharmacodynamic and Clinical Effects: The times to onset of pharmacologic effect and to peak effect
of preparations of LANOXIN are shown in Table 2. Documented for ventricular
response rate in atrial fibrillation, inotropic effects and electrocardiographic
changes. Depending
upon rate of infusion.<br/>Hemodynamic Effects: Digoxin produces hemodynamic improvement in patients with
heart failure. Short- and long-term therapy with the drug increases cardiac
output and lowers pulmonary artery pressure, pulmonary capillary wedge pressure,
and systemic vascular resistance. These hemodynamic effects are accompanied
by an increase in the left ventricular ejection fraction and a decrease in
end-systolic and end-diastolic dimensions.<br/>Chronic Heart Failure: Two 12-week, double-blind, placebo-controlled studies enrolled
178 (RADIANCE trial) and 88 (PROVED trial) patients with NYHA class II or
III heart failure previously treated with digoxin, a diuretic, and an ACE
inhibitor (RADIANCE only) and randomized them to placebo or treatment with
LANOXIN Tablets. Both trials demonstrated better preservation of exercise
capacity in patients randomized to LANOXIN. Continued treatment with LANOXIN
reduced the risk of developing worsening heart failure, as evidenced by heart
failure-related hospitalizations and emergency care and the need for concomitant
heart failure therapy. The larger study also showed treatment-related benefits
in NYHA class and patients' global assessment. In the smaller trial,
these trended in favor of a treatment benefit. The
Digitalis Investigation Group (DIG) main trial was a multicenter, randomized,
double-blind, placebo-controlled mortality study of 6,801 patients with
heart failure and left ventricular ejection fraction���0.45. At randomization,
67% were NYHA class I or II, 71% had heart failure of ischemic etiology, 44%
had been receiving digoxin, and most were receiving concomitant ACE inhibitor
(94%) and diuretic (82%). Patients were randomized to placebo or LANOXIN Tablets,
the dose of which was adjusted for the patient's age, sex, lean body
weight, and serum creatinine (see DOSAGE AND ADMINISTRATION), and followed
for up to 58 months (median 37 months). The median daily dose prescribed
was 0.25 mg. Overall all-cause mortality was 35% with no difference between
groups (95% confidence limits for relative risk of 0.91 to 1.07). LANOXIN
was associated with a 25% reduction in the number of hospitalizations for
heart failure, a 28% reduction in the risk of a patient having at least one
hospitalization for heart failure, and a 6.5% reduction in total hospitalizations
(for any cause). Use of LANOXIN was associated with
a trend to increase time to all-cause death or hospitalization. The trend
was evident in subgroups of patients with mild heart failure as well as more
severe disease, as shown in Table 3. Although the effect on all-cause
death or hospitalization was not statistically significant, much of the apparent
benefit derived from effects on mortality and hospitalization attributed to
heart failure. Number of patients with
an event during the first 2 years per 1,000 randomized patients. Relative risk (95% confidence interval). DIG Ancillary Study In situations where there is no statistically
significant benefit of treatment evident from a trial's primary endpoint,
results pertaining to a secondary endpoint should be interpreted cautiously.<br/>Chronic Atrial Fibrillation: In patients with chronic atrial fibrillation, digoxin slows
rapid ventricular response rate in a linear dose-response fashion from 0.25
to 0.75 mg/day. Digoxin should not be used for the treatment of multifocal
atrial tachycardia.
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dailymed-instance:activeIng... | |
dailymed-instance:contraind... |
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.
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dailymed-instance:supply |
LANOXICAPS (digoxin solution in capsules), 100 mcg
(0.1 mg): Bottle of 100 (NDC 0173-0272-55). Imprint B2C (yellow). LANOXICAPS
(digoxin solution in capsules), 200 mcg (0.2 mg): Bottle of 100
(NDC 0173-0274-55). Imprint C2C (green). Store
at 25��C (77��F); excursions permitted to 15 to 30��C (59 to 86��F)
[see USP Controlled Room Temperature] in a dry place and protect from light. Manufactured by Cardinal
Health St. Petersburg, FL 33702 for
GlaxoSmithKline Research Triangle Park, NC 27709 ��2005,
GlaxoSmithKline. All rights reserved. June 2005 RL-2173
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dailymed-instance:genericDr... | |
dailymed-instance:activeMoi... | |
dailymed-instance:inactiveI... |
dailymed-ingredient:D&C_Yellow_No._10,
dailymed-ingredient:edible_black_ink,
dailymed-ingredient:ethyl_alcohol,
dailymed-ingredient:gelatin,
dailymed-ingredient:glycerin,
dailymed-ingredient:methylparaben,
dailymed-ingredient:polyethylene_glycol_400,
dailymed-ingredient:propylene_glycol,
dailymed-ingredient:propylparaben,
dailymed-ingredient:sorbitol,
dailymed-ingredient:water
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dailymed-instance:precautio... |
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.<br/>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.<br/>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.<br/>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.<br/>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.<br/>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.<br/>Drug Interactions: Potassium-depleting diuretics are a major contributing factor to digitalis toxicity. Calcium, particularly if administered rapidly
by the intravenous route, may produce serious arrhythmias in digitalized patients. Quinidine, verapamil, amiodarone, propafenone, indomethacin, itraconazole , alprazolam,and spironolactone raise the serum digoxin concentration due to a reduction in clearance
and/or in volume of distribution of the drug, with the implication that digitalis
intoxication may result. Erythromycin and clarithromycin (and possibly other macrolide antibiotics) and tetracycline may increase digoxin absorption in patients who inactivate digoxin
by bacterial metabolism in the lower intestine, so that digitalis intoxication
may result. The risk of this interaction may be reduced if digoxin is given
as LANOXICAPS (see CLINICAL PHARMACOLOGY: Absorption). Propantheline and diphenoxylate, by decreasing
gut motility, may increase digoxin absorption. Antacids, kaolin-pectin, sulfasalazine, neomycin, cholestyramine, certain anticancer drugs, and metoclopramide may interfere with intestinal digoxin absorption, resulting in
unexpectedly low serum concentrations. Rifampin may decrease serum digoxin concentration, especially in patients
with renal dysfunction, by increasing the non-renal clearance of digoxin.
There have been inconsistent reports regarding the effects of other drugs
[e.g., quinine, penicillamine] on serum digoxin concentration. Thyroid administration to a digitalized, hypothyroid patient may increase
the dose requirement of digoxin. Concomitant use of digoxin and sympathomimetics increases the risk of cardiac arrhythmias. Succinylcholine may cause a sudden extrusion of potassium from muscle cells, and
may thereby cause arrhythmias in digitalized patients. Although beta-adrenergic
blockers or calcium channel blockers and digoxin may be useful in combination
to control atrial fibrillation, their additive effects on AV node conduction
can result in advanced or complete heart block. Due
to the considerable variability of these interactions, the dosage of digoxin
should be individualized when patients receive these medications concurrently.
Furthermore, caution should be exercised when combining digoxin with any drug
that may cause a significant deterioration in renal function, since a decline
in glomerular filtration or tubular secretion may impair the excretion ofdigoxin.<br/>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.<br/>Carcinogenesis, Mutagenesis, 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.<br/>Pregnancy:<br/>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 reproduction
capacity. Digoxin should be given to a pregnant woman only if clearly needed.<br/>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.<br/>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.<br/>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).
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dailymed-instance:overdosag... |
Treatment of Adverse Reactions Produced by Overdosage: Digoxin should be temporarily discontinued until the adverse
reaction resolves. Every effort should also be made to correct factors that
may contribute to the adverse reaction (such as electrolyte disturbances or
concurrent medications). Once the adverse reaction has resolved, therapy with
digoxin may be reinstituted, following a careful reassessment of dose. Withdrawal
of digoxin may be all that is required to treat the adverse reaction. However,
when the primary manifestation of digoxin overdosage is a cardiac arrhythmia,
additional therapy may be needed. If the rhythm disturbance
is a symptomatic bradyarrhythmia or heart block, consideration should be given
to the reversal of toxicity with DIGIBIND' [Digoxin Immune Fab (Ovine)]
(see below), the use of atropine, or the insertion of a temporary cardiac
pacemaker. However, asymptomatic bradycardia or heart block related to digoxin
may require only temporary withdrawal of the drug and cardiac monitoring of
the patient. If the rhythm disturbance is a ventricular
arrhythmia, consideration should be given to the correction of electrolyte
disorders, particularly if hypokalemia (see below) or hypomagnesemia is present.
DIGIBIND is a specific antidote for digoxin and may be used to reverse potentially
life-threatening ventricular arrhythmias due to digoxin overdosage.<br/>Administration of Potassium: Every effort should be made to maintain the serum potassium
concentration between 4.0 and 5.5 mmol/L. Potassium is usually administered
orally, but when correction of the arrhythmia is urgent and the serum potassium
concentration is low, potassium may be administered cautiously by the intravenous
route. The electrocardiogram should be monitored for any evidence of potassium
toxicity (e.g., peaking of T waves) and to observe the effect on the arrhythmia.
Potassium salts may be dangerous in patients who manifest bradycardia or heart
block due to digoxin (unless primarily related to supraventricular tachycardia)
and in the setting of massive digitalis overdosage (see Massive Digitalis
Overdosage subsection).<br/>Massive Digitalis Overdosage: Manifestations of life-threatening toxicity include ventricular
tachycardia or ventricular fibrillation, or progressive bradyarrhythmias,
or heart block. The administration of more than 10 mg of digoxin in a
previously healthy adult, or more than 4 mg in a previously healthy child,
or a steady-state serum concentration greater than 10 ng/mL, often results
in cardiac arrest. DIGIBIND should be used to reverse
the toxic effects of ingestion of a massive overdose. The decision to administer
DIGIBIND to a patient who has ingested a massive dose of digoxin but who has
not yet manifested life-threatening toxicity should depend on the likelihood
that life-threatening toxicity will occur (see above). Patients
with massive digitalis ingestion should receive large doses of activated charcoal
to prevent absorption and bind digoxin in the gut during enteroenteric recirculation.
Emesis or gastric lavage may be indicated especially if ingestion has occurred
within 30 minutes of the patient's presentation at the hospital.
Emesis should not be induced in patients who are obtunded. If a patient presents
more than 2 hours after ingestion or already has toxic manifestations,
it may be unsafe to induce vomiting or attempt passage of a gastric tube,
because such maneuvers may induce an acute vagal episode that can worsen digitalis-related
arrhythmias. Severe digitalis intoxication can cause
a massive shift of potassium from inside to outside the cell, leading to life-threatening
hyperkalemia. The administration of potassium supplements in the setting of
massive intoxication may be hazardous and should be avoided. Hyperkalemia
caused by massive digitalis toxicity is best treated with DIGIBIND; initial
treatment with glucose and insulin may also be required if hyperkalemia itself
is acutely life-threatening.
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dailymed-instance:genericMe... |
digoxin
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dailymed-instance:fullName |
LANOXICAPS (Capsule, Liquid Filled)
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dailymed-instance:adverseRe... |
In general, the adverse reactions of digoxin are dose-dependent
and occur at doses higher than those needed to achieve a therapeutic effect.
Hence, adverse reactions are less common when digoxin is used within the recommended
dose range or therapeutic serum concentration range and when there is careful
attention to concurrent medications and conditions. Because
some patients may be particularly susceptible to side effects with digoxin,
the dosage of the drug should always be selected carefully and adjusted as
the clinical condition of the patient warrants. In the past, when high doses
of digoxin were used and little attention was paid to clinical status or concurrent
medications, adverse reactions to digoxin were more frequent and severe. Cardiac
adverse reactions accounted for about one half, gastrointestinal disturbances
for about one fourth, and CNS and other toxicity for about one fourth of these
adverse reactions. However, available evidence suggests that the incidence
and severity of digoxin toxicity has decreased substantially in recent years.
In recent controlled clinical trials, in patients with predominantly mild
to moderate heart failure, the incidence of adverse experiences was comparable
in patients taking digoxin and in those taking placebo. In a large mortality
trial, the incidence of hospitalization for suspected digoxin toxicity was
2% in patients taking LANOXIN Tablets compared to 0.9% in patients taking
placebo. In this trial, the most common manifestations of digoxin toxicity
included gastrointestinal and cardiac disturbances; CNS manifestations were
less common.<br/>Adults:<br/>Cardiac: Therapeutic doses of digoxin may cause heart block in patients
with pre-existing sinoatrial or AV conduction disorders; heart block can be
avoided by adjusting the dose of digoxin. Prophylactic use of a cardiac pacemaker
may be considered if the risk of heart block is considered unacceptable. High
doses of digoxin may produce a variety of rhythm disturbances, such as first-degree,
second-degree (Wenckebach), or third-degree heart block (including asystole);
atrial tachycardia with block; AV dissociation; accelerated junctional (nodal)
rhythm; unifocal or multiform ventricular premature contractions (especially
bigeminy or trigeminy); ventricular tachycardia; and ventricular fibrillation.
Digoxin produces PR prolongation and ST segment depression which should not
by themselves be considered digoxin toxicity. Cardiac toxicity can also occur
at therapeutic doses in patients who have conditions which may alter their
sensitivity to digoxin (see WARNINGS and PRECAUTIONS).<br/>Gastrointestinal: Digoxin may cause anorexia, nausea, vomiting, and diarrhea.
Rarely, the use of digoxin has been associated with abdominal pain, intestinal
ischemia, and hemorrhagic necrosis of the intestines.<br/>CNS: Digoxin can produce visual disturbances (blurred or yellow
vision), headache, weakness, dizziness, apathy, confusion, and mental disturbances
(such as anxiety, depression, delirium, and hallucination).<br/>Other: Gynecomastia has been occasionally observed following the
prolonged use of digoxin. Thrombocytopenia and maculopapular rash and other
skin reactions have been rarely observed. The following
table summarizes the incidence of those adverse experiences listed above for
patients treated with LANOXIN Tablets or placebo from two randomized, double-blind,
placebo-controlled withdrawal trials. Patients in these trials were also receiving
diuretics with or without angiotensin-converting enzyme inhibitors. These
patients had been stable on digoxin, and were randomized to digoxin or placebo.
The results shown in Table 4 reflect the experience in patients following
dosage titration with the use of serum digoxin concentrations and careful
follow-up. These adverse experiences are consistent with results from a large,
placebo-controlled mortality trial (DIG trial) wherein over half the patients
were not receiving digoxin prior to enrollment.<br/>Infants and Children: The side effects of digoxin in infants and children differ
from those seen in adults in several respects. Although digoxin may produce
anorexia, nausea, vomiting, diarrhea, and CNS disturbances in young patients,
these are rarely the initial symptoms of overdosage. Rather, the earliest
and most frequent manifestation of excessive dosing with digoxin in infants
and children is the appearance of cardiac arrhythmias, including sinus bradycardia.
In children, the use of digoxin may produce any arrhythmia. The most common
are conduction disturbances or supraventricular tachyarrhythmias, such as
atrial tachycardia (with or without block) and junctional (nodal) tachycardia.
Ventricular arrhythmias are less common. Sinus bradycardia may be a sign of
impending digoxin intoxication, especially in infants, even in the absence
of first-degree heart block. Any arrhythmia or alteration in cardiac conductionthat develops in a child taking digoxin should be assumed to be caused by
digoxin, until further evaluation proves otherwise.
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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.<br/>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.<br/>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.
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Heart Failure: LANOXIN is indicated for the treatment of mild to moderate
heart failure. LANOXIN increases left ventricular ejection fraction and improves
heart failure symptoms as evidenced by exercise capacity and heart failure-related
hospitalizations and emergency care, while having no effect on mortality.
Where possible, LANOXIN should be used with a diuretic and an angiotensin-converting
enzyme inhibitor, but an optimal order for starting these 3 drugs cannot
be specified.<br/>Atrial Fibrillation: LANOXIN is indicated for the control of ventricular response
rate in patients with chronic atrial fibrillation.
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LANOXICAPS
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