digoxin 125 MCG Oral Tablet
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.
Digoxin should generally be avoided in these patients, although it has been used for ventricular rate control in the subgroup of patients with atrial fibrillation.
DRUG INTERACTIONS
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 (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 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.
Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate.
Concomitant use can increase the risk of bradycardia.
Digoxin concentrations are increased by about 15% when digoxin and carvedilol are administered concomitantly.
Therefore, increased monitoring of digoxin is recommended when initiating, adjusting, or discontinuing carvedilol.
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 of digoxin.
OVERDOSAGE
Signs and Symptoms The signs and symptoms of toxicity are generally similar to those described in the ADVERSE REACTIONS section but may be more frequent and can be more severe.
Signs and symptoms of digoxin toxicity become more frequent with levels above 2 ng/mL.
However, in deciding whether a patient’s symptoms are due to digoxin, the clinical state together with serum electrolyte levels and thyroid function are important factors (see DOSAGE AND ADMINISTRATION ).
Adults In adults without heart disease, clinical observation suggests that an overdose of digoxin of 10 to 15 mg was the dose resulting in death of half of the patients.
If more than 25 mg of digoxin was ingested by an adult without heart disease, death or progressive toxicity responsive only to digoxin-binding Fab antibody fragments resulted.
Cardiac manifestations are the most frequent and serious sign of both acute and chronic toxicity.
Peak cardiac effects generally occur 3 to 6 hours following overdosage and may persist for the ensuing 24 hours or longer.
Digoxin toxicity may result in almost any type of arrhythmia (see ADVERSE REACTIONS ).
Multiple rhythm disturbances in the same patient are common.
Cardiac arrest from asystole or ventricular fibrillation due to digoxin toxicity is usually fatal.
Among the extra-cardiac manifestations, gastrointestinal symptoms (e.g.
nausea, vomiting, anorexia) are very common (up to 80% incidence) and precede cardiac manifestations in approximately half of the patients in most literature reports.
Neurologic manifestations (e.g.
dizziness, various CNS disturbances), fatigue, and malaise are very common.
Visual manifestations may also occur with aberration in color vision (predominance of yellow green) the most frequent.
Neurological and visual symptoms may persist after other signs of toxicity have resolved.
In chronic toxicity, non-specific extra-cardiac symptoms, such as malaise and weakness, may predominate.
Children In children aged 1 to 3 years without heart disease, clinical observation suggests that an overdose of digoxin of 6 to 10 mg was the dose resulting in death in half of the patients.
If more than 10 mg of digoxin was ingested by a child aged 1 to 3 years without heart disease, the outcome was uniformly fatal when Fab fragment treatment was not given.
Most manifestations of toxicity in children occur during or shortly after the loading phase with digoxin.
The same arrhythmias or combination of arrhythmias that occur in adults can occur in pediatrics.
Sinus tachycardia, supraventricular tachycardia, and rapid atrial fibrillation are seen less frequently in the pediatric population.
Pediatric patients are more likely to present with an AV conduction disturbance or a sinus bradycardia.
Any arrhythmia or alteration in cardiac conduction that develops in a child taking digoxin should be assumed to be caused by digoxin, until further evaluation proves otherwise.
The frequent extracardiac manifestations similar to those seen in adults are gastrointestinal, CNS, and visual.
However, nausea and vomiting are not frequent in infants and small children.
In addition to the undesirable effects seen with recommended doses, weight loss in older age groups and failure to thrive in infants, abdominal pain due to mesenteric artery ischemia, drowsiness, and behavioral disturbances including psychotic manifestations have been reported in overdose.
Treatment In addition to cardiac monitoring, digoxin should be temporarily discontinued until the adverse reaction resolves and may be all that is required to treat the adverse reaction such as in asymptomatic bradycardia or digoxin-related heart block.
Every effort should also be made to correct factors that may contribute to the adverse reaction (such as electrolyte disturbances, thyroid function, or concurrent medications) (see WARNINGS and PRECAUTIONS: Drug Interactions ).
Once the adverse reaction has resolved, therapy with digoxin may be reinstituted, following a careful reassessment of dose.
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 Digoxin Immune Fab (Ovine) [Digibind or Digifab] (see Massive Digitalis Overdosage subsection), the use of atropine, or the insertion of a temporary cardiac pacemaker.
Digoxin Immune Fab (Ovine) is a specific antidote for digoxin and may be used to reverse potentially life-threatening ventricular arrhythmias due to digoxin overdosage.
If the rhythm disturbance is a ventricular arrhythmia, consideration should be given to the correction of electrolyte disorders, particularly if hypokalemia (see Administration of Potassium subsection) or hypomagnesemia is present.
Ventricular arrhythmias may respond to lidocaine or phenytoin.
Administration of Potassium Before administering potassium in digoxin overdose for hypokalemia, the serum potassium must be known and every effort should be made to maintain the serum potassium concentration between 4 and 5.5 mmol/L.
Potassium salts should be avoided as they 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.
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.
Massive Digitalis Overdosage Manifestations of life-threatening toxicity include ventricular tachycardia or ventricular fibrillation, or progressive bradyarrhythmias, or heart block.
Digoxin Immune Fab (Ovine) should be used to reverse the toxic effects of ingestion of a massive overdose.
The decision to administer Digoxin Immune Fab (Ovine) 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).
Digoxin is not effectively removed from the body by dialysis due to its large extravascular volume of distribution.
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 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 because such maneuvers may induce an acute vagal episode that can worsen digitalis-related arrhythmias.
In cases where a large amount of digoxin has been ingested, hyperkalemia may be present due to release of potassium from skeletal muscle.
Hyperkalemia caused by massive digitalis toxicity is best treated with Digoxin Immune Fab (Ovine); initial treatment with glucose and insulin may also be required if hyperkalemia itself is acutely life-threatening.
DESCRIPTION
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 2 portions: a sugar and a cardenolide (hence “glycosides”).
Digoxin is described chemically as (3β,5β,12β)-3-[(O-2,6-dideoxy-β-D-ribo-hexopyranosyl-(1→4)-O-2,6-dideoxy-β-D-ribo-hexopyranosyl-(1→4)-2,6-dideoxy-β-D-ribo-hexopyranosyl)oxy]-12,14-dihydroxy-card-20(22)-enolide.
Its molecular formula is C41H64O14, 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.
Digoxin is supplied as 125-mcg (0.125-mg) or 250-mcg (0.25-mg) tablets for oral administration.
Each tablet contains the labeled amount of digoxin, USP and the following inactive ingredients: lactose monohydrate, magnesium stearate, microcrystalline cellulose, corn starch.
The 125-mcg (0.125-mg) strength contains FD&C Yellow #5 (tartrazine).
Chemical Structure
HOW SUPPLIED
Digoxin tablets USP, 125 mcg (0.125 mg) are light yellow, round, flat-faced beveled edge tablets debossed with “981” on top of bisect on one side and plain on the other side.
Bottles of 100………………………………………………………………………..
NDC 0115-9811-01 Bottles of 500………………………………………………………………………..
NDC 0115-9811-02 Bottles of 1000………………………………………………………………………
NDC 0115-9811-03 Digoxin tablets USP, 250 mcg (0.25 mg) are off-white to light tan, round, convex tablets debossed with “982” on top of bisect on one side and plain on the other side.
Bottles of 100………………………………………………………………………..
NDC 0115-9822-01 Bottles of 500………………………………………………………………………..
NDC 0115-9822-02 Bottles of 1000………………………………………………………………………
NDC 0115-9822-03 Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature].
Dispense in tightly-closed, light-resistant container as defined in the USP, with child-resistant closure, as required.
GERIATRIC USE
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 ).
MECHANISM OF ACTION
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 an important factor in digitalis toxicity.
INDICATIONS AND USAGE
Heart Failure Digoxin is indicated for the treatment of mild to moderate heart failure.
Digoxin 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, digoxin should be used with a diuretic and an angiotensin converting enzyme inhibitor, but an optimal order for starting these 3 drugs cannot be specified.
Atrial Fibrillation Digoxin is indicated for the control of ventricular response rate in patients with chronic atrial fibrillation.
PEDIATRIC USE
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.
PREGNANCY
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.
NUSRING MOTHERS
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 breastfeeding 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.
DOSAGE AND ADMINISTRATION
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.
In selecting a dose of digoxin, the following factors must be considered: 1.The body weight of the patient.
Doses should be calculated based upon lean (i.e., ideal) body weight.
2.The patient’s renal function, preferably evaluated on the basis of estimated creatinine clearance.
3.The patient’s age.
Infants and children require different doses of digoxin than adults.
Also, advanced age may be indicative of diminished renal function even in patients with normal serum creatinine concentration (i.e., below 1.5 mg/dL).
4.Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharmacodynamic profile of digoxin (see PRECAUTIONS ).
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 (lower serum trough concentrations of 0.5 to 1 ng/mL may be appropriate in some adult patients, see Maintenance Dosing ).
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: 1.Analytical problems in the assay procedure.
2.Inappropriate serum sampling time.
3.Administration of a digitalis glycoside other than digoxin.
4.Conditions (described in WARNINGS and PRECAUTIONS ) causing an alteration in the sensitivity of the patient to digoxin.
5.Serum digoxin concentration may decrease acutely during periods of exercise without any associated change in clinical efficacy due to increased binding of digoxin to skeletal muscle.
Heart Failure Adults Digitalization may be accomplished by either of 2 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.
1.If rapid digitalization is considered medically appropriate, it may be achieved by administering a loading dose based upon projected peak digoxin body stores.
Maintenance dose can be calculated as a percentage of the loading dose.
2.More gradual digitalization may be obtained by beginning an appropriate maintenance dose, thus allowing digoxin body stores to accumulate slowly.
Steady-state serum digoxin concentrations will be achieved in approximately 5 half-lives of the drug for the individual patient.
Depending upon the patient’s renal function, this will take between 1 and 3 weeks.
Rapid Digitalization With a Loading Dose Peak digoxin body stores of 8 to 12 mcg/kg should provide therapeutic effect with minimum risk of toxicity in most patients with heart failure and normal sinus rhythm.
Because of altered digoxin distribution and elimination, projected peak body stores for patients with renal insufficiency should be conservative (i.e., 6 to 10 mcg/kg) (see PRECAUTIONS ).
The loading dose should be administered in several portions, with roughly half the total given as the first dose.
Additional fractions of this planned total dose may be given at 6- to 8-hour intervals, with careful assessment of clinical response before each additional dose.
If the patient’s clinical response necessitates a change from the calculated loading dose of digoxin, then calculation of the maintenance dose should be based upon the amount actually given.
A single initial dose of 500 to 750 mcg (0.5 to 0.75 mg) of digoxin tablets usually produces a detectable effect in 0.5 to 2 hours that becomes maximal in 2 to 6 hours.
Additional doses of 125 to 375 mcg (0.125 to 0.375 mg) may be given cautiously at 6- to 8-hour intervals until clinical evidence of an adequate effect is noted.
The usual amount of digoxin tablets that a 70-kg patient requires to achieve 8 to 12 mcg/kg peak body stores is 750 to 1,250 mcg (0.75 to 1.25 mg).
Digoxin injection is frequently used to achieve rapid digitalization, with conversion to digoxin tablets for maintenance therapy.
If patients are switched from intravenous to oral digoxin formulations, allowances must be made for differences in bioavailability when calculating maintenance dosages (see Table 1, CLINICAL PHARMACOLOGY ).
Maintenance Dosing The doses of digoxin used in controlled trials in patients with heart failure have ranged from 125 to 500 mcg (0.125 to 0.5 mg) once daily.
In these studies, the digoxin dose has been generally titrated according to the patient’s age, lean body weight, and renal function.
Therapy is generally initiated at a dose of 250 mcg (0.25 mg) once daily in patients under age 70 with good renal function, at a dose of 125 mcg (0.125 mg) once daily in patients over age 70 or with impaired renal function, and at a dose of 62.5 mcg (0.0625 mg) in patients with marked renal impairment.
Doses may be increased every 2 weeks according to clinical response.
In a subset of approximately 1,800 patients enrolled in the DIG trial (wherein dosing was based on an algorithm similar to that in Table 5) the mean (± SD) serum digoxin concentrations at 1 month and 12 months were 1.01 ± 0.47 ng/mL and 0.97± 0.43 ng/mL, respectively.
There are no rigid guidelines as to the range of serum concentrations that are most efficacious.
Several post hoc analyses of heart failure patients in the DIG trial suggest that the optimal trough digoxin serum level may be 0.5 ng/mL to 1 ng/mL.
The maintenance dose should be based upon the percentage of the peak body stores lost each day through elimination.
The following formula has had wide clinical use: Maintenance Dose = Peak Body Stores (i.e., Loading Dose) × % Daily Loss/100 Where: % Daily Loss = 14 + Ccr/5 (Ccr is creatinine clearance, corrected to 70 kg body weight or 1.73 m2 body surface area.) Table 5 provides average daily maintenance dose requirements of digoxin tablets for patients with heart failure based upon lean body weight and renal function: Table 5.
Usual Daily Maintenance Dose Requirements (mcg) of Digoxin for Estimated Peak Body Stores of 10 mcg/kg Lean Body Weight Number of Days Before Steady State Achieved If no loading dose administered.
Corrected Ccr kg 50 60 70 80 90 100 (mL/min per 70 kg) Ccr is creatinine clearance, corrected to 70-kg body weight or 1.73 m2 body surface area.
For adults, if only serum creatinine concentrations (Scr) are available, a Ccr (corrected to 70 kg body weight) may be estimated in men as (140 – Age)/Scr.
For women, this result should be multiplied by 0.85.
Note: This equation cannot be used for estimating creatinine clearance in infants or children.
lb 110 132 154 176 198 220 0 62.562.5 mcg = 0.0625 mg 125 125 125 187.5 187.5 22 10 125 125 125 187.5 187.5 187.5 19 20 125 125 187.5 187.5 187.5 250 16 30 125 187.5 187.5 187.5 250 250 14 40 125 187.5 187.5 250 250 250 13 50 187.5 187.5 250 250 250 250 12 60 187.5 187.5 250 250 250 375 11 70 187.5 250 250 250 250 375 10 80 187.5 250 250 250 375 375 9 90 187.5 250 250 250 375 500 8 100 250 250 250 375 375 500 7 Example: Based on Table 5, a patient in heart failure with an estimated lean body weight of 70 kg and a Ccr of 60 mL/min should be given a dose of 250 mcg (0.25 mg) daily of digoxin tablets, usually taken after the morning meal.
If no loading dose is administered, steady-state serum concentrations in this patient should be anticipated at approximately 11 days.
Infants and Children In general, divided daily dosing is recommended for infants and young children (under age 10).
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: Table 6.
Daily Maintenance Doses in Children With Normal Renal Function Age Daily Maintenance Dose (mcg/kg) 2 to 5 Years 10 to 15 5 to 10 Years 7 to 10 Over 10 Years 3 to 5 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.
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.
Dosage Adjustment When Changing Preparations The difference in bioavailability between digoxin injection or digoxin tablets must be considered when changing patients from one dosage form to the other.