Digoxin
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Uses
DIGOXIN is indicated for the treatment of mild to moderate heart failure in adults. DIGOXIN increases left ventricular ejection fraction and improves heart failure symptoms as evidenced by improved exercise capacity and decreased heart failure-related hospitalizations and emergency care, while having no effect on mortality. Where possible, DIGOXIN should be used in combination with a diuretic and an angiotensin-converting enzyme (ACE) inhibitor.
Digoxin increases myocardial contractility in pediatric patients with heart failure.
DIGOXIN is indicated for the control of ventricular response rate in adult patients with chronic atrial fibrillation.
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Other Information
DIGOXIN (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 (scored) and 250 mcg (scored) tablets for oral administration. Each tablet contains the labeled amount of digoxin USP and the following inactive ingredients: corn and potato starches, lactose and magnesium stearate. The 125 mcg tablets contain D&C Yellow No. 10 and FD&C Yellow No. 6.
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Digoxin Manufacturers
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State Of Florida Doh Central Pharmacy
![Digoxin Tablet [State Of Florida Doh Central Pharmacy]](/wp-content/themes/bootstrap/assets/img/loading2.gif)
Digoxin | State Of Florida Doh Central Pharmacy
2.1 Important Dosing and Administration InformationIn selecting a DIGOXIN dosing regimen, it is important to consider factors that affect digoxin blood levels (e.g., body weight, age, renal function, concomitant drugs) since toxic levels of digoxin are only slightly higher than therapeutic levels. Dosing can be either initiated with a loading dose followed by maintenance dosing if rapid titration is desired or initiated with maintenance dosing without a loading dose.
Consider interruption or reduction in DIGOXIN digoxin dose prior to electrical cardioversion [see Warnings and Precautions (5.4)].
Use digoxin solution to obtain the appropriate dose in infants, young pediatric patients, or patients with very low body weight.
2.2 Loading Dosing Regimen in Adults and Pediatric PatientsFor adults and pediatric patients if a loading dosage is to be given, administer half the total loading dose initially, then ¼ the loading dose every 6-8 hours twice, with careful assessment of clinical response and toxicity before each dose. The recommended loading dose is displayed in Table 1.
Table 1. Recommended DIGOXIN Oral Loading Dose mcg = microgramAge
Total Oral Loading Dose (mcg/kg)
Administer half the total loading dose initially,
then ¼ the loading dose every 6 to 8 hours twice5 to 10 years
20-45
Adults and pediatric patients over 10 years
10-15
2.3 Maintenance Dosing in Adults and Pediatric Patients Over 10 Years OldThe maintenance dose is based on lean body weight, renal function, age, and concomitant products [see Clinical Pharmacology (12.3)].
The recommended starting maintenance dose in adults and pediatric patients over 10 years old with normal renal function is given in Table 2. Doses may be increased every 2 weeks according to clinical response, serum drug levels, and toxicity.
Table 2. Recommended Starting DIGOXIN Maintenance Dosage in Adults and Pediatric Patients Over 10 Years Old mcg = microgramAge
Total Oral Maintenance Dose, mcg/kg/day
(given once daily)Adults and pediatric patients over 10 years
3.4-5.1
Table 3 provides the recommended (once daily) maintenance dose for adults and pediatric patients over 10 years old (to be given once daily) according to lean body weight and renal function. The doses are based on studies in adult patients with heart failure. Alternatively, the maintenance dose may be estimated by the following formula (peak body stores lost each day through elimination):
Total Maintenance Dose = Loading Dose (i.e., Peak Body Stores) x % Daily Loss/100
(% Daily Loss = 14 + Creatinine clearance/5)Reduce the dose of DIGOXIN in patients whose lean weight is an abnormally small fraction of their total body mass because of obesity or edema.
Table 3. Recommended Maintenance Dose (in micrograms given once daily) of DIGOXIN in Pediatric Patients Over 10 Years Old and Adults by Lean Body Weight and by Renal Functiona a Doses are rounded to the nearest dose possible using whole DIGOXIN tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed.
b For adults, creatinine clearance was corrected to 70-kg body weight or 1.73 m2 body surface area. If only serum creatinine concentrations (Scr) are available, a corrected Ccr may be estimated in men as (140 – Age)/Scr. For women, this result should be multiplied by 0.85.
For pediatric patients, the modified Schwartz equation may be used. The formula is based on height in cm and Scr in mg/dL where k is a constant. Ccr is corrected to 1.73 m2 body surface area. During the first year of life, the value of k is 0.33 for pre-term babies and 0.45 for term infants. The k is 0.55 for pediatric patients and adolescent girls and 0.7 for adolescent boys.
GFR (mL/min/1.73 m2) = (k x Height)/Scr
c If no loading dose administered.
d The doses listed assume average body composition.Corrected
Creatinine
ClearancebLean Body Weightd
Number of Days
Before Steady
State Achievedckg
40
50
60
70
80
90
100
10 mL/min 62.5* 125 125 187.5 187.5 187.5 250 19 20 mL/min 125 125 125 187.5 187.5 250 250 16 30 mL/min 125 125 187.5 187.5 250 250 312.5 14 40 mL/min 125 187.5 187.5 250 250 312.5 312.5 13 50 mL/min 125 187.5 187.5 250 250 312.5 312.5 12 60 mL/min 125 187.5 250 250 312.5 312.5 375 11 70 mL/min 187.5 187.5 250 250 312.5 375 375 10 80 mL/min 187.5 187.5 250 312.5 312.5 375 437.5 9 90 mL/min 187.5 250 250 312.5 375 437.5 437.5 8 100 mL/min 187.5 250 312.5 312.5 375 437.5 500 7 2.4 Maintenance Dosing in Pediatric Patients Less Than 10 Years OldThe starting maintenance dose for heart failure in pediatric patients less than 10 years old is based on lean body weight, renal function, age, and concomitant products [see Clinical Pharmacology (12.3)]. The recommended starting maintenance dose for pediatric patients between 5 years and 10 years old is given in Table 4. These recommendations assume the presence of normal renal function.
Table 4. Recommended Starting DIGOXIN Oral Maintenance Dosage in Pediatric Patients between 5 and 10 Years OldAge
Oral Maintenance Dose,
mcg/kg/dose5 years to 10 years
3.2-6.4 Twice daily
Table 5 provides average daily maintenance dose requirements for pediatric patients between 5 and 10 years old (to be given twice daily) with heart failure based on age, lean body weight, and renal function.
Table 5. Recommended Maintenance Dose (in micrograms given TWICE daily) of DIGOXIN in Pediatric Patients between 5 and 10 Years of Agea Based upon Lean Body Weight and Renal Functiona,b a Recommended are doses to be given twice daily.
b The doses are rounded to the nearest dose possible using whole DIGOXIN tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed.
c The modified Schwartz equation may be used to estimate creatinine clearance. See footnote b under Table 3.
d If no loading dose administered.Corrected
Creatinine
ClearancecLean Body Weight
Number of Days
Before Steady
State Achieveddkg
20
30
40
50
60
10 mL/min - 62.5 62.5* 125 125 19 20 mL/min 62.5 62.5 125 125 125 16 30 mL/min 62.5 62.5* 125 125 187.5 14 40 mL/min 62.5 62.5* 125 187.5 187.5 13 50 mL/min 62.5 125 125 187.5 187.5 12 60 mL/min 62.5 125 125 187.5 250 11 70 mL/min 62.5 125 187.5 187.5 250 10 80 mL/min 62.5* 125 187.5 187.5 250 9 90 mL/min 62.5* 125 187.5 250 250 8 100 mL/min 62.5* 125 187.5 250 312.5 7 2.5 Monitoring to Assess Safety, Efficacy, and Therapeutic Blood LevelsMonitor for signs and symptoms of digoxin toxicity and clinical response. Adjust dose based on toxicity, efficacy, and blood levels.
Serum digoxin levels less than 0.5 ng/mL have been associated with diminished efficacy, while levels above 2 ng/mL have been associated with increased toxicity without increased benefit.
Interpret the serum digoxin concentration in the overall clinical context, and do not use an isolated measurement of serum digoxin concentration as the basis for increasing or decreasing the DIGOXIN dose. Serum digoxin concentrations may be falsely elevated by endogenous digoxin-like substances [see Drug Interactions (7.4)]. If the assay is sensitive to these substances, consider obtaining a baseline digoxin level before starting DIGOXIN and correct post-treatment values by the reported baseline level.
Obtain serum digoxin concentrations just before the next scheduled DIGOXIN dose or at least 6 hours after the last dose. The digoxin concentration is likely to be 10-25% lower when sampled right before the next dose (24 hours after dosing) compared to sampling 8 hours after dosing (using once-daily dosing). However, there will be only minor differences in digoxin concentrations using twice daily dosing whether sampling is done at 8 or 12 hours after a dose.
2.6 Switching from Intravenous Digoxin to Oral DigoxinWhen switching from intravenous to oral digoxin formulations, make allowances for differences in bioavailability when calculating maintenance dosages (see Table 6).
Table 6. Comparison of the Systemic Availability and Equivalent Doses of Oral and Intravenous DIGOXINAbsolute
BioavailabilityEquivalent Doses (mcg)
DIGOXIN Tablets
60-80%
62.5
125
250
500
DIGOXIN Intravenous Injection
100%
50
100
200
400
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American Health Packaging
Digoxin | American Health Packaging
2.1 Important Dosing and Administration InformationIn selecting a digoxin tablets dosing regimen, it is important to consider factors that affect digoxin blood levels (e.g., body weight, age, renal function, concomitant drugs) since toxic levels of digoxin are only slightly higher than therapeutic levels. Dosing can be either initiated with a loading dose followed by maintenance dosing if rapid titration is desired or initiated with maintenance dosing without a loading dose.
Consider interruption or reduction in digoxin tablets dose prior to electrical cardioversion [see Warnings and Precautions (5.4)].
Use digoxin solution to obtain the appropriate dose in infants, young pediatric patients, or patients with very low body weight.
2.2 Loading Dosing Regimen in Adults and Pediatric PatientsFor adults and pediatric patients if a loading dosage is to be given, administer half the total loading dose initially, then ¼ the loading dose every 6 to 8 hours twice, with careful assessment of clinical response and toxicity before each dose. The recommended loading dose is displayed in Table 1.
Table 1. Recommended Digoxin Tablets Oral Loading Dose Mcg = microgramAge
Total Oral Loading Dose (mcg/kg)
Administer half the total loading dose
initially, then ¼ the loading dose every
6 to 8 hours twice5 to 10 years
20 to 45
Adults and pediatric patients over
10 years10 to 15
2.3 Maintenance Dosing in Adults and Pediatric Patients Over 10 Years OldThe maintenance dose is based on lean body weight, renal function, age, and concomitant products [see Clinical Pharmacology (12.3)].
The recommended starting maintenance dose in adults and pediatric patients over 10 years old with normal renal function is given in Table 2. Doses may be increased every 2 weeks according to clinical response, serum drug levels, and toxicity.
Table 2. Recommended Starting Digoxin Tablets Maintenance Dosage in Adults and Pediatric Patients Over 10 Years Old mcg = microgramAge
Total Oral Maintenance Dose,
mcg/kg/day (given once daily)Adults and pediatric patients over
10 years3.4 to 5.1
Table 3 provides the recommended (once daily) maintenance dose for adults and pediatric patients over 10 years old (to be given once daily) according to lean body weight and renal function. The doses are based on studies in adult patients with heart failure. Alternatively, the maintenance dose may be estimated by the following formula (peak body stores lost each day through elimination):
Total Maintenance Dose = Loading Dose (i.e., Peak Body Stores) × % Daily Loss/100
(% Daily Loss = 14 + Creatinine clearance/5)Reduce the dose of digoxin tablets in patients whose lean weight is an abnormally small fraction of their total body mass because of obesity or edema.
Table 3. Recommended Maintenance Dose (in micrograms given once daily) of Digoxin Tablets in Pediatric Patients Over 10 Years Old and Adults by Lean Body Weight and by Renal Functiona Corrected Creatinine Clearanceb Lean Body Weightd Number of Days Before Steady State Achievedc kg 40 50 60 70 80 90 100 a Doses are rounded to the nearest dose possible using whole and/or half digoxin tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed.
b For adults, creatinine clearance was corrected to 70-kg body weight or 1.73 m2 body surface area. If only serum creatinine concentrations (Scr) are available, a corrected Ccr may be estimated in men as (140 – Age)/Scr. For women, this result should be multiplied by 0.85.
For pediatric patients, the modified Schwartz equation may be used. The formula is based on height in cm and Scr in mg/dL where k is a constant. Ccr is corrected to 1.73 m2 body surface area. During the first year of life, the value of k is 0.33 for pre-term babies and 0.45 for term infants. The k is 0.55 for pediatric patients and adolescent girls and 0.7 for adolescent boys.
GFR (mL/min/1.73 m2) = (k × Height)/Scr
c If no loading dose administered.
d The doses listed assume average body composition.10 mL/min
62.5*
125
125
187.5
187.5
187.5
250
19
20 mL/min
125
125
125
187.5
187.5
250
250
16
30 mL/min
125
125
187.5
187.5
250
250
312.5
14
40 mL/min
125
187.5
187.5
250
250
312.5
312.5
13
50 mL/min
125
187.5
187.5
250
250
312.5
312.5
12
60 mL/min
125
187.5
250
250
312.5
312.5
375
11
70 mL/min
187.5
187.5
250
250
312.5
375
375
10
80 mL/min
187.5
187.5
250
312.5
312.5
375
437.5
9
90 mL/min
187.5
250
250
312.5
375
437.5
437.5
8
100 mL/min
187.5
250
312.5
312.5
375
437.5
500
7
2.4 Maintenance Dosing in Pediatric Patients Less Than 10 Years OldThe starting maintenance dose for heart failure in pediatric patients less than 10 years old is based on lean body weight, renal function, age, and concomitant products [see Clinical Pharmacology (12.3)]. The recommended starting maintenance dose for pediatric patients between 5 years and 10 years old is given in Table 4. These recommendations assume the presence of normal renal function.
Table 4. Recommended Starting Digoxin Tablets Oral Maintenance Dosage in Pediatric Patients between 5 and 10 Years Old Age Oral Maintenance Dose, mcg/kg/dose5 years to 10 years
3.2 to 6.4 Twice daily
Table 5 provides average daily maintenance dose requirements for pediatric patients between 5 and 10 years old (to be given twice daily) with heart failure based on age, lean body weight, and renal function.
Table 5. Recommended Maintenance Dose (in micrograms given TWICE daily) of Digoxin Tablets in Pediatric Patients between 5 and 10 Years of Agea Based upon Lean Body Weight and Renal Functiona,b Corrected Creatinine Clearancec Lean Body Weight Number of Days Before Steady State Achievedd kg 20 30 40 50 60 a Recommended are doses to be given twice daily.
b The doses are rounded to the nearest dose possible using whole and/or half digoxin tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed.
c The modified Schwartz equation may be used to estimate creatinine clearance. See footnote b under Table 3.
d If no loading dose administered.10 mL/min
-
62.5
62.5*
125
125
19
20 mL/min
62.5
62.5
125
125
125
16
30 mL/min
62.5
62.5*
125
125
187.5
14
40 mL/min
62.5
62.5*
125
187.5
187.5
13
50 mL/min
62.5
125
125
187.5
187.5
12
60 mL/min
62.5
125
125
187.5
250
11
70 mL/min
62.5
125
187.5
187.5
250
10
80 mL/min
62.5*
125
187.5
187.5
250
9
90 mL/min
62.5*
125
187.5
250
250
8
100 mL/min
62.5*
125
187.5
250
312.5
7
2.5 Monitoring to Assess Safety, Efficacy, and Therapeutic Blood LevelsMonitor for signs and symptoms of digoxin toxicity and clinical response. Adjust dose based on toxicity, efficacy, and blood levels.
Serum digoxin levels less than 0.5 ng/mL have been associated with diminished efficacy, while levels above 2 ng/mL have been associated with increased toxicity without increased benefit.
Interpret the serum digoxin concentration in the overall clinical context, and do not use an isolated measurement of serum digoxin concentration as the basis for increasing or decreasing the digoxin tablets dose. Serum digoxin concentrations may be falsely elevated by endogenous digoxin-like substances [see Drug Interactions (7.4)]. If the assay is sensitive to these substances, consider obtaining a baseline digoxin level before starting digoxin tablets and correct post-treatment values by the reported baseline level.
Obtain serum digoxin concentrations just before the next scheduled digoxin tablets dose or at least 6 hours after the last dose. The digoxin concentration is likely to be 10 to 25% lower when sampled right before the next dose (24 hours after dosing) compared to sampling 8 hours after dosing (using once-daily dosing). However, there will be only minor differences in digoxin concentrations using twice daily dosing whether sampling is done at 8 or 12 hours after a dose.
2.6 Switching from Intravenous Digoxin to Oral DigoxinWhen switching from intravenous to oral digoxin formulations, make allowances for differences in bioavailability when calculating maintenance dosages (see Table 6).
Table 6. Comparison of the Systemic Availability and Equivalent Doses of Oral and Intravenous Digoxin Tablets Absolute Bioavailability Equivalent Doses (mcg)Digoxin Tablets
60 to 80%
62.5
125
250
500
Digoxin Intravenous Injection
100%
50
100
200
400
-
Major Pharmaceuticals
Digoxin | Major Pharmaceuticals
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:
The body weight of the patient. Doses should be calculated based upon lean (i.e., ideal) body weight. The patient's renal function, preferably evaluated on the basis of estimated creatinine clearance. 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). Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharma-codynamic 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 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 ng/mL. However, since one-third of patients with clinical toxicity have concentrations less than 2 ng/mL, values below 2 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:
Analytical problems in the assay procedure. Inappropriate serum sampling time. Administration of a digitalis glycoside other than digoxin. Conditions (described in WARNINGS and PRECAUTIONS) causing an alteration in the sensitivity of the patient to digoxin. 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 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.
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 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 five 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 1250 mcg (0.75 to 1.25 mg).
Digoxin Injection is frequently used to achieve rapid digitalization with conversion to digoxin tablets or digoxin solution in capsules 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 1800 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.
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) x % 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* 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.
† lf no loading dose administered.
‡ 62.5 mcg = 0.0625 mg
Corrected Ccr Lean Body Weight Number of (mL/min kg 50 60 70 80 90 100 Days Before per 70 kg)* lb 110 132 154 176 198 220 Steady State Achieved† 0 62.5‡ 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 7Example: 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 5In 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 digox-in 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 solution in capsules and digoxin pediatric elixir or digoxin 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 digoxin solution in capsules are approximately equivalent to 125 mcg (0.125 mg) and 250 mcg (0.25 mg) doses of digoxin tablets and digoxin pediatric elixir, respectively (see Table 1 in CLINICAL PHARMACOLOGY: Pharmacokinetics).
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Caraco Pharmaceutical Laboratories, Ltd.
Digoxin | Novartis Consumer Health, Inc.
• do not use more than directed • adults: take 2 caplets with a glass of water • if symptoms persist or worsen, ask your doctor • do not take more than 2 caplets in 24 hours, unless directed by a doctor • under 18 years of age: ask a doctor -
State Of Florida Doh Central Pharmacy
Digoxin | State Of Florida Doh Central Pharmacy
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:
The body weight of the patient. Doses should be calculated based upon lean (i.e., ideal) body weight. The patient's renal function, preferably evaluated on the basis of estimated creatinine clearance. 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). Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharma-codynamic 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 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 ng/mL. However, since one-third of patients with clinical toxicity have concentrations less than 2 ng/mL, values below 2 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:
Analytical problems in the assay procedure. Inappropriate serum sampling time. Administration of a digitalis glycoside other than digoxin. Conditions (described in WARNINGS and PRECAUTIONS) causing an alteration in the sensitivity of the patient to digoxin. 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 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.
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 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 five 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 1250 mcg (0.75 to 1.25 mg).
Digoxin Injection is frequently used to achieve rapid digitalization with conversion to digoxin tablets or digoxin solution in capsules 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 1800 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.
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) x % 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* 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.
† lf no loading dose administered.
‡ 62.5 mcg = 0.0625 mg
Corrected Ccr Lean Body Weight Number of (mL/min kg 50 60 70 80 90 100 Days Before per 70 kg)* lb 110 132 154 176 198 220 Steady State Achieved† 0 62.5‡ 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 7Example: 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 5In 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 digox-in 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 solution in capsules and digoxin pediatric elixir or digoxin 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 digoxin solution in capsules are approximately equivalent to 125 mcg (0.125 mg) and 250 mcg (0.25 mg) doses of digoxin tablets and digoxin pediatric elixir, respectively (see Table 1 in CLINICAL PHARMACOLOGY: Pharmacokinetics).
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State Of Florida Doh Central Pharmacy
Digoxin | State Of Florida Doh Central Pharmacy
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:
The body weight of the patient. Doses should be calculated based upon lean (i.e., ideal) body weight. The patient's renal function, preferably evaluated on the basis of estimated creatinine clearance. 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). Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharma-codynamic 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 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 ng/mL. However, since one-third of patients with clinical toxicity have concentrations less than 2 ng/mL, values below 2 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:
Analytical problems in the assay procedure. Inappropriate serum sampling time. Administration of a digitalis glycoside other than digoxin. Conditions (described in WARNINGS and PRECAUTIONS) causing an alteration in the sensitivity of the patient to digoxin. 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 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.
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 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 five 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 1250 mcg (0.75 to 1.25 mg).
Digoxin Injection is frequently used to achieve rapid digitalization with conversion to digoxin tablets or digoxin solution in capsules 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 1800 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.
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) x % 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* 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.
† lf no loading dose administered.
‡ 62.5 mcg = 0.0625 mg
Corrected Ccr Lean Body Weight Number of (mL/min kg 50 60 70 80 90 100 Days Before per 70 kg)* lb 110 132 154 176 198 220 Steady State Achieved† 0 62.5‡ 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 7Example: 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 5In 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 digox-in 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 solution in capsules and digoxin pediatric elixir or digoxin 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 digoxin solution in capsules are approximately equivalent to 125 mcg (0.125 mg) and 250 mcg (0.25 mg) doses of digoxin tablets and digoxin pediatric elixir, respectively (see Table 1 in CLINICAL PHARMACOLOGY: Pharmacokinetics).
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Rebel Distributors Corp
Digoxin | Rebel Distributors Corp
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:
The body weight of the patient. Doses should be calculated based upon lean (i.e., ideal) body weight. The patient's renal function, preferably evaluated on the basis of estimated creatinine clearance. 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). Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharma-codynamic 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 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 ng/mL. However, since one-third of patients with clinical toxicity have concentrations less than 2 ng/mL, values below 2 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:
Analytical problems in the assay procedure. Inappropriate serum sampling time. Administration of a digitalis glycoside other than digoxin. Conditions (described in WARNINGS and PRECAUTIONS ) causing an alteration in the sensitivity of the patient to digoxin. 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 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.
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 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 five 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 1250 mcg (0.75 to 1.25 mg).
Digoxin Injection is frequently used to achieve rapid digitalization with conversion to digoxin tablets or digoxin solution in capsules 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 1800 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.
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:
Table 5 provides average daily maintenance dose requirements of digoxin tablets for patients with heart failure based upon lean body weight and renal function:
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:
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 digox-in 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 solution in capsules and digoxin pediatric elixir or digoxin 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 digoxin solution in capsules are approximately equivalent to 125 mcg (0.125 mg) and 250 mcg (0.25 mg) doses of digoxin tablets and digoxin pediatric elixir, respectively (see Table 1 in CLINICAL PHARMACOLOGY: Pharmacokinetics ).
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Remedyrepack Inc.
Digoxin | Remedyrepack Inc.
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 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 ng/mL. However, since one-third of patients with clinical toxicity have concentrations less than 2 ng/mL, values below 2 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 WARNINGSand 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 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.
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 five 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 1250 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 1800 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 1.010.47 ng/mL and 0.970.43 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) x% Daily Loss100Where: % 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 Tablets for Estimated Peak Body Stores of 10 mcg/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.lf no loading dose administered.62.5 mcg = 0.0625 mgCorrected CcrLean Body WeightNumber of(mL/minkg5060708090100Days Beforeper 70 kg)*lb110132154176198220Steady State Achieved062.5125125125187.5187.52210125125125187.5187.5187.51920125125187.5187.5187.52501630125187.5187.5187.52502501440125187.5187.52502502501350187.5187.52502502502501260187.5187.52502502503751170187.52502502502503751080187.5250250250375375990187.525025025037550081002502502503753755007
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
AgeDaily Maintenance Dose(mcg/kg)2 to 5 Years10 to 155 to 10 Years7 to 10Over 10 Years3 to 5In 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 another.
Doses of 100 mcg (0.1. mg) and 200 mcg (0.2 mg) of digoxin solution in capsules are approximately equivalent to 125 mcg (0.125 mg) and 250 mcg (0.25 mg) doses of digoxin tablets and digoxin pediatric elixir, respectively (see Table 1 in CLINICAL PHARMACOLOGY: Pharmacokinetics).
-
Mckesson Contract Packaging
Digoxin | Mckesson Contract Packaging
GeneralRecommended 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:
The body weight of the patient. Doses should be calculated based upon lean (i.e., ideal) body weight. The patient's renal function, preferably evaluated on the basis of estimated creatinine clearance. 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). Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharmacodynamic profile of digoxin (see PRECAUTIONS). Serum Digoxin ConcentrationsIn 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 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 ng/mL. However, since one-third of patients with clinical toxicity have concentrations less than 2 ng/mL, values below 2 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:
Analytical problems in the assay procedure. Inappropriate serum sampling time. Administration of a digitalis glycoside other than digoxin. Conditions (described in WARNINGS and PRECAUTIONS) causing an alteration in the sensitivity of the patient to digoxin. 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: AdultsDigitalization 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.
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 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 five 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 DosePeak 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 1250 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 DosingThe 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 1800 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) x % 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 Tablets for Estimated Peak Body Stores of 10 mcg/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.
† lf no loading dose administered.
‡ 62.5 mcg = 0.0625 mg
Corrected Ccr Lean Body Weight Number of (mL/min kg 50 60 70 80 90 100 Days Before per 70 kg)* lb 110 132 154 176 198 220 Steady State Achieved† 0 62.5‡ 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 ExampleBased 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 ChildrenIn 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 5In 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 FibrillationPeak 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 PreparationsThe difference in bioavailability between Digoxin Injection or Digoxin 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 digoxin solution in capsules are approximately equivalent to 125 mcg (0.125 mg) and 250 mcg (0.25 mg) doses of digoxin tablets and digoxin pediatric elixir, respectively (see Table 1 in CLINICAL PHARMACOLOGY: Pharmacokinetics).
-
Physicians Total Care, Inc.
Digoxin | Physicians Total Care, Inc.
GeneralRecommended 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:
The body weight of the patient. Doses should be calculated based upon lean (i.e., ideal) body weight. The patient's renal function, preferably evaluated on the basis of estimated creatinine clearance. 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). Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharmacodynamic profile of digoxin (see PRECAUTIONS). Serum Digoxin ConcentrationsIn 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 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 ng/mL. However, since one-third of patients with clinical toxicity have concentrations less than 2 ng/mL, values below 2 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:
Analytical problems in the assay procedure. Inappropriate serum sampling time. Administration of a digitalis glycoside other than digoxin. Conditions (described in WARNINGS and PRECAUTIONS) causing an alteration in the sensitivity of the patient to digoxin. 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: AdultsDigitalization 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.
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. 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 five 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 DosePeak 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 1250 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 DosingThe 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 1800 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) x % 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 Tablets for Estimated Peak Body Stores of 10 mcg/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.
† lf no loading dose administered.
‡ 62.5 mcg = 0.0625 mg
Corrected Ccr Lean Body Weight Number of (mL/min kg 50 60 70 80 90 100 Days Before per 70 kg)* lb 110 132 154 176 198 220 Steady State Achieved† 0 62.5‡ 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 ExampleBased 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 ChildrenIn 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 5In 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 FibrillationPeak 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 PreparationsThe difference in bioavailability between Digoxin Injection or Digoxin 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 digoxin solution in capsules are approximately equivalent to 125 mcg (0.125 mg) and 250 mcg (0.25 mg) doses of digoxin tablets and digoxin pediatric elixir, respectively (see Table 1 in CLINICAL PHARMACOLOGY: Pharmacokinetics).
-
Jerome Stevens Pharmaceuticals, Inc.
Digoxin | Jerome Stevens Pharmaceuticals, Inc.
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:
The body weight of the patient. Doses should be calculated based upon lean (i.e., ideal) body weight. The patient’s renal function, preferably evaluated on the basis of estimated creatinine clearance. 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). 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. 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:
Analytical problems in the assay procedure. Inappropriate serum sampling time. Administration of a digitalis glycoside other than digoxin Conditions (described in WARNINGS and PRECAUTIONS) causing an alteration in the sensitivity of the patient to digoxin. 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 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.
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. 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 five 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 1250 mcg (0.75 to 1.25 mg).
Digoxin Injection is frequently used to achieve rapid digitalization, with conversion to digoxin tablets or digoxin solution in capsules 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 1800 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.
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)
x % 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 *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.
†If no loading dose administered.
‡ 62.5 mcg = 0.0625 mg Lean Body WeightCorrected Ccr
kg 50
(mL/min per 70 kg)*
lb 110 60
132 70
154 80
176 90
198 100
220 Number of Days Before
Steady State Achieved† 0 62.5‡ 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 7Example: 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 5In children with renal disease, digoxin must be carefully titrated based upon clinical response.
It cannot be overemphasized that both 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 bio-availability between Digoxin Injection or Digoxin Solution in Capsules and Digoxin Elixir Pediatric or Digoxin 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 Digoxin Solution in Capsules are approximately equivalent to 125 mcg (0.125 mg) and
250 mcg (0.25 mg) doses of Digoxin Tablets and Elixir Pediatric, respectively (see Table 1 in CLINICAL PHARMACOLOGY: Pharmacokinetics). -
Golden State Medical Supply, Inc.
Digoxin | Golden State Medical Supply, Inc.
GeneralRecommended 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:
The body weight of the patient. Doses should be calculated based upon lean (i.e., ideal) body weight. The patient's renal function, preferably evaluated on the basis of estimated creatinine clearance. 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). Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharmacodynamic profile of digoxin (see PRECAUTIONS). Serum Digoxin ConcentrationsIn 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 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 ng/mL. However, since one-third of patients with clinical toxicity have concentrations less than 2 ng/mL, values below 2 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:
Analytical problems in the assay procedure. Inappropriate serum sampling time. Administration of a digitalis glycoside other than digoxin. Conditions (described in WARNINGS and PRECAUTIONS) causing an alteration in the sensitivity of the patient to digoxin. 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: AdultsDigitalization 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.
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 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 five 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 DosePeak 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 1250 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 DosingThe 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 1800 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) x % 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 Tablets for Estimated Peak Body Stores of 10 mcg/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.
† lf no loading dose administered.
‡ 62.5 mcg = 0.0625 mg
Corrected Ccr Lean Body Weight Number of (mL/min kg 50 60 70 80 90 100 Days Before per 70 kg)* lb 110 132 154 176 198 220 Steady State Achieved† 0 62.5‡ 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 ExampleBased 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 ChildrenIn 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 5In 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 FibrillationPeak 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 PreparationsThe difference in bioavailability between Digoxin Injection or Digoxin 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 digoxin solution in capsules are approximately equivalent to 125 mcg (0.125 mg) and 250 mcg (0.25 mg) doses of digoxin tablets and digoxin pediatric elixir, respectively (see Table 1 in CLINICAL PHARMACOLOGY: Pharmacokinetics).
-
Pd-rx Pharmaceuticals, Inc.
Digoxin | Pd-rx Pharmaceuticals, Inc.
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:
The body weight of the patient. Doses should be calculated based upon lean (i.e., ideal) body weight. The patient’s renal function, preferably evaluated on the basis of estimated creatinine clearance. 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). 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. 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:
Analytical problems in the assay procedure. Inappropriate serum sampling time. Administration of a digitalis glycoside other than digoxin Conditions (described in WARNINGS and PRECAUTIONS) causing an alteration in the sensitivity of the patient to digoxin. 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 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.
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. 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 five 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 1250 mcg (0.75 to 1.25 mg).
Digoxin Injection is frequently used to achieve rapid digitalization, with conversion to digoxin tablets or digoxin solution in capsules 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 1800 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.
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)
x % 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 WeightCorrected Ccr
kg 50
(mL/min per 70 kg)
lb 110 60
132 70
154 80
176 90
198 100
220 Number of Days Before
Steady State Achieved 0 62.5 125 125 125 187.5 187.5 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 7Example: 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 5In children with renal disease, digoxin must be carefully titrated based upon clinical response.
It cannot be overemphasized that both 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 bio-availability between Digoxin Injection or Digoxin Solution in Capsules and Digoxin Elixir Pediatric or Digoxin 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 Digoxin Solution in Capsules are approximately equivalent to 125 mcg (0.125 mg) and
250 mcg (0.25 mg) doses of Digoxin Tablets and Elixir Pediatric, respectively (see Table 1 in CLINICAL PHARMACOLOGY: Pharmacokinetics). -
American Health Packaging
Digoxin | American Health Packaging
GeneralRecommended 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:
The body weight of the patient. Doses should be calculated based upon lean (i.e., ideal) body weight. The patient's renal function, preferably evaluated on the basis of estimated creatinine clearance. 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). Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharmacodynamic profile of digoxin (see PRECAUTIONS). Serum Digoxin ConcentrationsIn 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 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 ng/mL. However, since one-third of patients with clinical toxicity have concentrations less than 2 ng/mL, values below 2 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:
Analytical problems in the assay procedure. Inappropriate serum sampling time. Administration of a digitalis glycoside other than digoxin. Conditions (described in WARNINGS and PRECAUTIONS) causing an alteration in the sensitivity of the patient to digoxin. 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: AdultsDigitalization 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.
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 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 five 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 DosePeak 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 1250 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 DosingThe 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 1800 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) x % 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 Tablets for Estimated Peak Body Stores of 10 mcg/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.
† lf no loading dose administered.
‡ 62.5 mcg = 0.0625 mg
Corrected Ccr Lean Body Weight Number of (mL/min kg 50 60 70 80 90 100 Days Before per 70 kg)* lb 110 132 154 176 198 220 Steady State Achieved† 0 62.5‡ 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 ExampleBased 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 ChildrenIn 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 5In 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 FibrillationPeak 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 PreparationsThe difference in bioavailability between Digoxin Injection or Digoxin Tablets must be considered when changing patients from one dosage form to another.
-
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GeneralRecommended 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:
The body weight of the patient. Doses should be calculated based upon lean (i.e., ideal) body weight. The patient's renal function, preferably evaluated on the basis of estimated creatinine clearance. 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). Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharmacodynamic profile of digoxin (see PRECAUTIONS). Serum Digoxin ConcentrationsIn 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 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 ng/mL. However, since one-third of patients with clinical toxicity have concentrations less than 2 ng/mL, values below 2 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:
Analytical problems in the assay procedure. Inappropriate serum sampling time. Administration of a digitalis glycoside other than digoxin. Conditions (described in WARNINGS and PRECAUTIONS) causing an alteration in the sensitivity of the patient to digoxin. 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: AdultsDigitalization 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.
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. 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 five 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 DosePeak 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 1250 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 DosingThe 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 1800 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) x % 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 Tablets for Estimated Peak Body Stores of 10 mcg/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.
† lf no loading dose administered.
‡ 62.5 mcg = 0.0625 mg
Corrected Ccr Lean Body Weight Number of (mL/min kg 50 60 70 80 90 100 Days Before per 70 kg)* lb 110 132 154 176 198 220 Steady State Achieved† 0 62.5‡ 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 ExampleBased 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 ChildrenIn 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 5In 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 FibrillationPeak 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 PreparationsThe difference in bioavailability between Digoxin Injection or Digoxin 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 digoxin solution in capsules are approximately equivalent to 125 mcg (0.125 mg) and 250 mcg (0.25 mg) doses of digoxin tablets and digoxin pediatric elixir, respectively (see Table 1 in CLINICAL PHARMACOLOGY: Pharmacokinetics).
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GeneralRecommended 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:
The body weight of the patient. Doses should be calculated based upon lean (i.e., ideal) body weight. The patient's renal function, preferably evaluated on the basis of estimated creatinine clearance. 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). Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharmacodynamic profile of digoxin (see PRECAUTIONS). Serum Digoxin ConcentrationsIn 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 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 ng/mL. However, since one-third of patients with clinical toxicity have concentrations less than 2 ng/mL, values below 2 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:
Analytical problems in the assay procedure. Inappropriate serum sampling time. Administration of a digitalis glycoside other than digoxin. Conditions (described in WARNINGS and PRECAUTIONS) causing an alteration in the sensitivity of the patient to digoxin. 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: AdultsDigitalization 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.
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 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 five 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 DosePeak 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 1250 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 DosingThe 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 1800 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) x % 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 Tablets for Estimated Peak Body Stores of 10 mcg/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.
† lf no loading dose administered.
‡ 62.5 mcg = 0.0625 mg
Corrected Ccr Lean Body Weight Number of (mL/min kg 50 60 70 80 90 100 Days Before per 70 kg)* lb 110 132 154 176 198 220 Steady State Achieved† 0 62.5‡ 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 ExampleBased 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 ChildrenIn 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 5In 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 FibrillationPeak 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 PreparationsThe difference in bioavailability between Digoxin Injection or Digoxin Tablets must be considered when changing patients from one dosage form to another.
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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.
Parenteral administration of digoxin should be used only when the need for rapid digitalization is urgent or when the drug cannot be taken orally. Intramuscular injection can lead to severe pain at the injection site, thus intravenous administration is preferred. If the drug must be administered by the intramuscular route, it should be injected deep into the muscle followed by massage. No more than 500 mcg (2 mL) should be injected into a single site.
Digoxin Injection can be administered undiluted or diluted with a 4-fold or greater volume of Sterile Water for Injection, 0.9% Sodium Chloride Injection, or 5% Dextrose Injection. The use of less than a 4-fold volume of diluent could lead to precipitation of the digoxin. Immediate use of the diluted product is recommended.
If tuberculin syringes are used to measure very small doses, one must be aware of the problem of inadvertent overadministration of digoxin. The syringe should not be flushed with the parenteral solution after its contents are expelled into an indwelling vascular catheter.
Slow infusion of Digoxin Injection is preferable to bolus administration. Rapid infusion of digitalis glycosides has been shown to cause systemic and coronary arteriolar constriction, which may be clinically undesirable. Caution is thus advised and Digoxin Injection should probably be administered over a period of 5 minutes or longer. Mixing of Digoxin Injection with other drugs in the same container or simultaneous administration in the same intravenous line is not recommended.
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 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 ng/mL. However, since one-third of patients with clinical toxicity have concentrations less than 2 ng/mL, values below 2 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 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.
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 five 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
Digoxin Injection is frequently used to achieve rapid digitalization, with conversion to digoxin tablets or digoxin capsules 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, Pharmacokinetics and dosing Table 5 below).Intramuscular injection of digoxin is extremely painful and offers no advantages unless other routes of administration are contraindicated.
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 intravenous dose of 400 to 600 mcg (0.4 to 0.6 mg) of Digoxin Injection usually produces a detectable effect in 5 to 30 minutes that becomes maximal in 1 to 4 hours. Additional doses of 100 to 300 mcg (0.1 to 0.3 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 Injection that a 70-kg patient requires to achieve 8- to 12-mcg/kg peak body stores is 600 to 1000 mcg (0.6 to 1 mg).
Maintenance Dosing
The doses of oral 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 1800 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.
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) x % 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 Injection for patients with heart failure based upon lean body weight and renal function:
Lean Body Weight
Corrected Ccr
kg
50
60
70
80
90
100
Number of Days Before Steady State Achieved‡
(mL/min per 70 kg)†
lb
110
132
154
176
198
220
0
75§
75
100
100
125
150
22
10
75
100
100
125
150
150
19
20
100
100
125
150
150
175
16
30
100
125
150
150
175
200
14
40
100
125
150
175
200
225
13
50
125
150
175
200
225
250
12
60
125
150
175
200
225
250
11
70
150
175
200
225
250
275
10
80
150
175
200
250
275
300
9
90
150
200
225
250
300
325
8
100
175
200
250
275
300
350
7
* Daily maintenance doses have been rounded to the nearest 25-mcg increment† 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.‡ If no loading dose administered
§ 75 mcg = 0.075 mg
EXAMPLE: Based on the above table, 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 175 mcg (0.175 mg) daily of Digoxin Injection. If no loading dose is administered, steady-state serum concentrations in this patient should be anticipated at approximately 11 days
Infants and Children
See the full prescribing information for pediatric digoxin injection (not available from West-Ward) for specific recommendations.
It cannot be overemphasized that 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 injectable digoxin and oral digoxin must be considered when changing patients from one dosage form to another (see Table 1 in CLINICAL PHARMACOLOGY, Pharmacokinetics). Intramuscular injection of digoxin is extremely painful and offers no advantage unless other routes of administration are contraindicated.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
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Ncs Healthcare Of Ky, Inc Dba Vangard Labs
Digoxin | Ncs Healthcare Of Ky, Inc Dba Vangard Labs
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:
The body weight of the patient. Doses should be calculated based upon lean (i.e., ideal) body weight. The patient"s renal function, preferably evaluated on the basis of estimated creatinine clearance. 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). 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 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 ng/mL. However, since one-third of patients with clinical toxicity have concentrations less than 2 ng/mL, values below 2 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:
Analytical problems in the assay procedure. Inappropriate serum sampling time. Administration of a digitalis glycoside other than digoxin. Conditions (described in WARNINGS and PRECAUTIONS) causing an alteration in the sensitivity of the patient to digoxin. 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 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.
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. 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 five 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 1250 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 1800 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) x % 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 Tablets for Estimated Peak Body Stores of 10 mcg/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.
† lf no loading dose administered.
‡ 62.5 mcg = 0.0625 mg
Corrected Ccr Lean Body Weight Number of (mL/min kg 50 60 70 80 90 100 Days Before per 70 kg)* lb 110 132 154 176 198 220 Steady State Achieved† 0 62.5‡ 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 7Example: 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 5In 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.
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Ncs Healthcare Of Ky, Inc Dba Vangard Labs
Digoxin | Ncs Healthcare Of Ky, Inc Dba Vangard Labs
GeneralRecommended 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:
The body weight of the patient. Doses should be calculated based upon lean (i.e., ideal) body weight. The patient's renal function, preferably evaluated on the basis of estimated creatinine clearance. 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). Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharmacodynamic profile of digoxin (see PRECAUTIONS). Serum Digoxin ConcentrationsIn 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 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 ng/mL. However, since one-third of patients with clinical toxicity have concentrations less than 2 ng/mL, values below 2 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:
Analytical problems in the assay procedure. Inappropriate serum sampling time. Administration of a digitalis glycoside other than digoxin. Conditions (described in WARNINGS and PRECAUTIONS) causing an alteration in the sensitivity of the patient to digoxin. 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: AdultsDigitalization 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.
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. 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 five 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 DosePeak 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 1250 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 DosingThe 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 1800 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) x % 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 Tablets for Estimated Peak Body Stores of 10 mcg/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.
† lf no loading dose administered.
‡ 62.5 mcg = 0.0625 mg
Corrected Ccr Lean Body Weight Number of (mL/min kg 50 60 70 80 90 100 Days Before per 70 kg)* lb 110 132 154 176 198 220 Steady State Achieved† 0 62.5‡ 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 ExampleBased 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 ChildrenIn 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 5In 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 FibrillationPeak 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 PreparationsThe difference in bioavailability between Digoxin Injection or Digoxin 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 digoxin solution in capsules are approximately equivalent to 125 mcg (0.125 mg) and 250 mcg (0.25 mg) doses of digoxin tablets and digoxin pediatric elixir, respectively (see Table 1 in CLINICAL PHARMACOLOGY: Pharmacokinetics).
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A-s Medication Solutions Llc
Digoxin | A-s Medication Solutions Llc
GeneralRecommended 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:
The body weight of the patient. Doses should be calculated based upon lean (i.e., ideal) body weight. The patient's renal function, preferably evaluated on the basis of estimated creatinine clearance. 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). Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharmacodynamic profile of digoxin (see PRECAUTIONS). Serum Digoxin ConcentrationsIn 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 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 ng/mL. However, since one-third of patients with clinical toxicity have concentrations less than 2 ng/mL, values below 2 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:
Analytical problems in the assay procedure. Inappropriate serum sampling time. Administration of a digitalis glycoside other than digoxin. Conditions (described in WARNINGS and PRECAUTIONS) causing an alteration in the sensitivity of the patient to digoxin. 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: AdultsDigitalization 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.
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. 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 five 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 DosePeak 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 1250 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 DosingThe 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 1800 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) x % 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 Tablets for Estimated Peak Body Stores of 10 mcg/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.
† lf no loading dose administered.
‡ 62.5 mcg = 0.0625 mg
Corrected Ccr Lean Body Weight Number of (mL/min kg 50 60 70 80 90 100 Days Before per 70 kg)* lb 110 132 154 176 198 220 Steady State Achieved† 0 62.5‡ 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 ExampleBased 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 ChildrenIn 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 5In 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 FibrillationPeak 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 PreparationsThe difference in bioavailability between Digoxin Injection or Digoxin 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 digoxin solution in capsules are approximately equivalent to 125 mcg (0.125 mg) and 250 mcg (0.25 mg) doses of digoxin tablets and digoxin pediatric elixir, respectively (see Table 1 in CLINICAL PHARMACOLOGY: Pharmacokinetics).
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Cardinal Health
Digoxin | Cardinal Health
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:
The body weight of the patient. Doses should be calculated based upon lean (i.e., ideal) body weight. The patient's renal function, preferably evaluated on the basis of estimated creatinine clearance. 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). Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharma-codynamic 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 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 ng/mL. However, since one-third of patients with clinical toxicity have concentrations less than 2 ng/mL, values below 2 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:
Analytical problems in the assay procedure. Inappropriate serum sampling time. Administration of a digitalis glycoside other than digoxin. Conditions (described in WARNINGS and PRECAUTIONS) causing an alteration in the sensitivity of the patient to digoxin. 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 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.
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 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 five 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 1250 mcg (0.75 to 1.25 mg).
Digoxin Injection is frequently used to achieve rapid digitalization with conversion to digoxin tablets or digoxin solution in capsules 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 1800 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.
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) x % 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* 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.
† lf no loading dose administered.
‡ 62.5 mcg = 0.0625 mg
Corrected Ccr Lean Body Weight Number of (mL/min kg 50 60 70 80 90 100 Days Before per 70 kg)* lb 110 132 154 176 198 220 Steady State Achieved† 0 62.5‡ 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 7Example: 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 5In 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 digox-in 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 solution in capsules and digoxin pediatric elixir or digoxin 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 digoxin solution in capsules are approximately equivalent to 125 mcg (0.125 mg) and 250 mcg (0.25 mg) doses of digoxin tablets and digoxin pediatric elixir, respectively (see Table 1 in CLINICAL PHARMACOLOGY: Pharmacokinetics).
-
Global Pharmaceuticals, Division Of Impax Laboratories Inc.
Digoxin | Global Pharmaceuticals, Division Of Impax Laboratories Inc.
2.1 Important Dosing and Administration InformationIn selecting a digoxin tablets dosing regimen, it is important to consider factors that affect digoxin blood levels (e.g., body weight, age, renal function, concomitant drugs) since toxic levels of digoxin are only slightly higher than therapeutic levels. Dosing can be either initiated with a loading dose followed by maintenance dosing if rapid titration is desired or initiated with maintenance dosing without a loading dose.
Consider interruption or reduction in digoxin tablets dose prior to electrical cardioversion [see Warnings and Precautions (5.4)].
Use digoxin solution to obtain the appropriate dose in infants, young pediatric patients, or patients with very low body weight.
2.2 Loading Dosing Regimen in Adults and Pediatric PatientsFor adults and pediatric patients if a loading dosage is to be given, administer half the total loading dose initially, then ¼ the loading dose every 6 to 8 hours twice, with careful assessment of clinical response and toxicity before each dose. The recommended loading dose is displayed in Table 1.
Table 1. Recommended Digoxin Tablets Oral Loading Dose Age Total Oral Loading Dose (mcg/kg)
Administer half the total loading dose initially, then ¼ the loading dose every 6 to 8 hours twice mcg = microgram 5 to 10 years 20 to 45 Adults and pediatric patients over 10 years 10 to 15 2.3 Maintenance Dosing in Adults and Pediatric Patients Over 10 Years OldThe maintenance dose is based on lean body weight, renal function, age, and concomitant products [see Clinical Pharmacology (12.3)].
The recommended starting maintenance dose in adults and pediatric patients over 10 years old with normal renal function is given in Table 2. Doses may be increased every 2 weeks according to clinical response, serum drug levels, and toxicity.
Table 2. Recommended Starting Digoxin Tablets Maintenance Dosage in Adults and Pediatric Patients Over 10 Years Old Age Total Oral Maintenance Dose, mcg/kg/day (given once daily) mcg = microgram Adults and pediatric patients over 10 years 3.4 to 5.1Table 3 provides the recommended (once daily) maintenance dose for adults and pediatric patients over 10 years old (to be given once daily) according to lean body weight and renal function. The doses are based on studies in adult patients with heart failure. Alternatively, the maintenance dose may be estimated by the following formula (peak body stores lost each day through elimination):
Total Maintenance Dose = Loading Dose (i.e., Peak Body Stores) × % Daily Loss/100
(% Daily Loss = 14 + Creatinine clearance/5)Reduce the dose of digoxin tablets in patients whose lean weight is an abnormally small fraction of their total body mass because of obesity or edema.
Table 3. Recommended Maintenance Dose (in micrograms given once daily) of Digoxin Tablets in Pediatric Patients Over 10 Years Old and Adults by Lean Body Weight and by Renal Function* Corrected Creatinine Clearance† Lean Body Weight‡ Number of Days Before Steady State Achieved§ kg 40 50 60 70 80 90 100 * Doses are rounded to the nearest dose possible using whole and/or half digoxin tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed. † For adults, creatinine clearance was corrected to 70-kg body weight or 1.73 m 2 body surface area. If only serum creatinine concentrations (Scr) are available, a corrected Ccr may be estimated in men as (140 – Age)/Scr. For women, this result should be multiplied by 0.85.
For pediatric patients, the modified Schwartz equation may be used. The formula is based on height in cm and Scr in mg/dL where k is a constant. Ccr is corrected to 1.73 m 2 body surface area. During the first year of life, the value of k is 0.33 for pre-term babies and 0.45 for term infants. The k is 0.55 for pediatric patients and adolescent girls and 0.7 for adolescent boys.
GFR (mL/min/1.73 m 2) = (k × Height)/Scr ‡ The doses listed assume average body composition. § If no loading dose administered. 10 mL/min 62.5* 125 125 187.5 187.5 187.5 250 19 20 mL/min 125 125 125 187.5 187.5 250 250 16 30 mL/min 125 125 187.5 187.5 250 250 312.5 14 40 mL/min 125 187.5 187.5 250 250 312.5 312.5 13 50 mL/min 125 187.5 187.5 250 250 312.5 312.5 12 60 mL/min 125 187.5 250 250 312.5 312.5 375 11 70 mL/min 187.5 187.5 250 250 312.5 375 375 10 80 mL/min 187.5 187.5 250 312.5 312.5 375 437.5 9 90 mL/min 187.5 250 250 312.5 375 437.5 437.5 8 100 mL/min 187.5 250 312.5 312.5 375 437.5 500 7 2.4 Maintenance Dosing in Pediatric Patients Less Than 10 Years OldThe starting maintenance dose for heart failure in pediatric patients less than 10 years old is based on lean body weight, renal function, age, and concomitant products [see Clinical Pharmacology (12.3)]. The recommended starting maintenance dose for pediatric patients between 5 years and 10 years old is given in Table 4. These recommendations assume the presence of normal renal function.
Table 4. Recommended Starting Digoxin Tablets Oral Maintenance Dosage in Pediatric Patients between 5 and 10 Years Old Age Oral Maintenance Dose, mcg/kg/dose 5 years to 10 years 3.2 to 6.4 Twice dailyTable 5 provides average daily maintenance dose requirements for pediatric patients between 5 and 10 years old (to be given twice daily) with heart failure based on age, lean body weight, and renal function.
Table 5. Recommended Maintenance Dose (in micrograms given TWICE daily) of Digoxin Tablets in Pediatric Patients between 5 and 10 Years of Agea Based upon Lean Body Weight and Renal Function*,† Corrected Creatinine Clearance‡ Lean Body Weight Number of Days Before Steady State Achieved§ kg 20 30 40 50 60 * Recommended are doses to be given twice daily. † The doses are rounded to the nearest dose possible using whole and/or half digoxin tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed. ‡ The modified Schwartz equation may be used to estimate creatinine clearance. See footnote b under Table 3. § If no loading dose administered. 10 mL/min - 62.5 62.5* 125 125 19 20 mL/min 62.5 62.5 125 125 125 16 30 mL/min 62.5 62.5* 125 125 187.5 14 40 mL/min 62.5 62.5* 125 187.5 187.5 13 50 mL/min 62.5 125 125 187.5 187.5 12 60 mL/min 62.5 125 125 187.5 250 11 70 mL/min 62.5 125 187.5 187.5 250 10 80 mL/min 62.5* 125 187.5 187.5 250 9 90 mL/min 62.5* 125 187.5 250 250 8 100 mL/min 62.5* 125 187.5 250 312.5 7 2.5 Monitoring to Assess Safety, Efficacy, and Therapeutic Blood LevelsMonitor for signs and symptoms of digoxin toxicity and clinical response. Adjust dose based on toxicity, efficacy, and blood levels.
Serum digoxin levels less than 0.5 ng/mL have been associated with diminished efficacy, while levels above 2 ng/mL have been associated with increased toxicity without increased benefit.
Interpret the serum digoxin concentration in the overall clinical context, and do not use an isolated measurement of serum digoxin concentration as the basis for increasing or decreasing the digoxin tablets dose. Serum digoxin concentrations may be falsely elevated by endogenous digoxin-like substances [see Drug Interactions (7.4)]. If the assay is sensitive to these substances, consider obtaining a baseline digoxin level before starting digoxin tablets and correct post-treatment values by the reported baseline level.
Obtain serum digoxin concentrations just before the next scheduled digoxin tablets dose or at least 6 hours after the last dose. The digoxin concentration is likely to be 10 to 25% lower when sampled right before the next dose (24 hours after dosing) compared to sampling 8 hours after dosing (using once-daily dosing). However, there will be only minor differences in digoxin concentrations using twice daily dosing whether sampling is done at 8 or 12 hours after a dose.
2.6 Switching from Intravenous Digoxin to Oral DigoxinWhen switching from intravenous to oral digoxin formulations, make allowances for differences in bioavailability when calculating maintenance dosages (see Table 6).
Table 6. Comparison of the Systemic Availability and Equivalent Doses of Oral and Intravenous Digoxin Tablets Absolute Bioavailability Equivalent Doses (mcg) Digoxin Tablets 60 to 80% 62.5 125 250 500 Digoxin Intravenous Injection 100% 50 100 200 400 -
Par Pharmaceutical, Inc
Digoxin | Par Pharmaceutical, Inc
2.1 Important Dosing and Administration InformationIn selecting a DIGOXIN dosing regimen, it is important to consider factors that affect digoxin blood levels (e.g., body weight, age, renal function, concomitant drugs) since toxic levels of digoxin are only slightly higher than therapeutic levels. Dosing can be either initiated with a loading dose followed by maintenance dosing if rapid titration is desired or initiated with maintenance dosing without a loading dose.
Consider interruption or reduction in DIGOXIN digoxin dose prior to electrical cardioversion [see Warnings and Precautions (5.4)].
Use digoxin solution to obtain the appropriate dose in infants, young pediatric patients, or patients with very low body weight.
2.2 Loading Dosing Regimen in Adults and Pediatric PatientsFor adults and pediatric patients if a loading dosage is to be given, administer half the total loading dose initially, then ¼ the loading dose every 6-8 hours twice, with careful assessment of clinical response and toxicity before each dose. The recommended loading dose is displayed in Table 1.
Table 1. Recommended DIGOXIN Oral Loading Dose mcg = microgramAge
Total Oral Loading Dose (mcg/kg)
Administer half the total loading dose initially,
then ¼ the loading dose every 6 to 8 hours twice5 to 10 years
20-45
Adults and pediatric patients over 10 years
10-15
2.3 Maintenance Dosing in Adults and Pediatric Patients Over 10 Years OldThe maintenance dose is based on lean body weight, renal function, age, and concomitant products [see Clinical Pharmacology (12.3)].
The recommended starting maintenance dose in adults and pediatric patients over 10 years old with normal renal function is given in Table 2. Doses may be increased every 2 weeks according to clinical response, serum drug levels, and toxicity.
Table 2. Recommended Starting DIGOXIN Maintenance Dosage in Adults and Pediatric Patients Over 10 Years Old mcg = microgramAge
Total Oral Maintenance Dose, mcg/kg/day
(given once daily)Adults and pediatric patients over 10 years
3.4-5.1
Table 3 provides the recommended (once daily) maintenance dose for adults and pediatric patients over 10 years old (to be given once daily) according to lean body weight and renal function. The doses are based on studies in adult patients with heart failure. Alternatively, the maintenance dose may be estimated by the following formula (peak body stores lost each day through elimination):
Total Maintenance Dose = Loading Dose (i.e., Peak Body Stores) x % Daily Loss/100
(% Daily Loss = 14 + Creatinine clearance/5)Reduce the dose of DIGOXIN in patients whose lean weight is an abnormally small fraction of their total body mass because of obesity or edema.
Table 3. Recommended Maintenance Dose (in micrograms given once daily) of DIGOXIN in Pediatric Patients Over 10 Years Old and Adults by Lean Body Weight and by Renal Functiona a Doses are rounded to the nearest dose possible using whole DIGOXIN tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed.
b For adults, creatinine clearance was corrected to 70-kg body weight or 1.73 m2 body surface area. If only serum creatinine concentrations (Scr) are available, a corrected Ccr may be estimated in men as (140 – Age)/Scr. For women, this result should be multiplied by 0.85.
For pediatric patients, the modified Schwartz equation may be used. The formula is based on height in cm and Scr in mg/dL where k is a constant. Ccr is corrected to 1.73 m2 body surface area. During the first year of life, the value of k is 0.33 for pre-term babies and 0.45 for term infants. The k is 0.55 for pediatric patients and adolescent girls and 0.7 for adolescent boys.
GFR (mL/min/1.73 m2) = (k x Height)/Scr
c If no loading dose administered.
d The doses listed assume average body composition.Corrected
Creatinine
ClearancebLean Body Weightd
Number of Days
Before Steady
State Achievedckg
40
50
60
70
80
90
100
10 mL/min 62.5* 125 125 187.5 187.5 187.5 250 19 20 mL/min 125 125 125 187.5 187.5 250 250 16 30 mL/min 125 125 187.5 187.5 250 250 312.5 14 40 mL/min 125 187.5 187.5 250 250 312.5 312.5 13 50 mL/min 125 187.5 187.5 250 250 312.5 312.5 12 60 mL/min 125 187.5 250 250 312.5 312.5 375 11 70 mL/min 187.5 187.5 250 250 312.5 375 375 10 80 mL/min 187.5 187.5 250 312.5 312.5 375 437.5 9 90 mL/min 187.5 250 250 312.5 375 437.5 437.5 8 100 mL/min 187.5 250 312.5 312.5 375 437.5 500 7 2.4 Maintenance Dosing in Pediatric Patients Less Than 10 Years OldThe starting maintenance dose for heart failure in pediatric patients less than 10 years old is based on lean body weight, renal function, age, and concomitant products [see Clinical Pharmacology (12.3)]. The recommended starting maintenance dose for pediatric patients between 5 years and 10 years old is given in Table 4. These recommendations assume the presence of normal renal function.
Table 4. Recommended Starting DIGOXIN Oral Maintenance Dosage in Pediatric Patients between 5 and 10 Years OldAge
Oral Maintenance Dose,
mcg/kg/dose5 years to 10 years
3.2-6.4 Twice daily
Table 5 provides average daily maintenance dose requirements for pediatric patients between 5 and 10 years old (to be given twice daily) with heart failure based on age, lean body weight, and renal function.
Table 5. Recommended Maintenance Dose (in micrograms given TWICE daily) of DIGOXIN in Pediatric Patients between 5 and 10 Years of Agea Based upon Lean Body Weight and Renal Functiona,b a Recommended are doses to be given twice daily.
b The doses are rounded to the nearest dose possible using whole DIGOXIN tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed.
c The modified Schwartz equation may be used to estimate creatinine clearance. See footnote b under Table 3.
d If no loading dose administered.Corrected
Creatinine
ClearancecLean Body Weight
Number of Days
Before Steady
State Achieveddkg
20
30
40
50
60
10 mL/min - 62.5 62.5* 125 125 19 20 mL/min 62.5 62.5 125 125 125 16 30 mL/min 62.5 62.5* 125 125 187.5 14 40 mL/min 62.5 62.5* 125 187.5 187.5 13 50 mL/min 62.5 125 125 187.5 187.5 12 60 mL/min 62.5 125 125 187.5 250 11 70 mL/min 62.5 125 187.5 187.5 250 10 80 mL/min 62.5* 125 187.5 187.5 250 9 90 mL/min 62.5* 125 187.5 250 250 8 100 mL/min 62.5* 125 187.5 250 312.5 7 2.5 Monitoring to Assess Safety, Efficacy, and Therapeutic Blood LevelsMonitor for signs and symptoms of digoxin toxicity and clinical response. Adjust dose based on toxicity, efficacy, and blood levels.
Serum digoxin levels less than 0.5 ng/mL have been associated with diminished efficacy, while levels above 2 ng/mL have been associated with increased toxicity without increased benefit.
Interpret the serum digoxin concentration in the overall clinical context, and do not use an isolated measurement of serum digoxin concentration as the basis for increasing or decreasing the DIGOXIN dose. Serum digoxin concentrations may be falsely elevated by endogenous digoxin-like substances [see Drug Interactions (7.4)]. If the assay is sensitive to these substances, consider obtaining a baseline digoxin level before starting DIGOXIN and correct post-treatment values by the reported baseline level.
Obtain serum digoxin concentrations just before the next scheduled DIGOXIN dose or at least 6 hours after the last dose. The digoxin concentration is likely to be 10-25% lower when sampled right before the next dose (24 hours after dosing) compared to sampling 8 hours after dosing (using once-daily dosing). However, there will be only minor differences in digoxin concentrations using twice daily dosing whether sampling is done at 8 or 12 hours after a dose.
2.6 Switching from Intravenous Digoxin to Oral DigoxinWhen switching from intravenous to oral digoxin formulations, make allowances for differences in bioavailability when calculating maintenance dosages (see Table 6).
Table 6. Comparison of the Systemic Availability and Equivalent Doses of Oral and Intravenous DIGOXINAbsolute
BioavailabilityEquivalent Doses (mcg)
DIGOXIN Tablets
60-80%
62.5
125
250
500
DIGOXIN Intravenous Injection
100%
50
100
200
400
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Remedyrepack Inc.
Digoxin | Remedyrepack Inc.
Digoxin tablets, USP dose is based on patient-specific factors (age, lean body weight, renal function, etc.). See full prescribing information. Monitor for toxicity and therapeutic effect. (2)
In selecting a digoxin tablets dosing regimen, it is important to consider factors that affect digoxin blood levels (e.g., body weight, age, renal function, concomitant drugs) since toxic levels of digoxin are only slightly higher than therapeutic levels. Dosing can be either initiated with a loading dose followed by maintenance dosing if rapid titration is desired or initiated with maintenance dosing without a loading dose.
Consider interruption or reduction in digoxin tablets dose prior to electrical cardioversion [see Warnings and Precautions (5.4)].
Use digoxin solution to obtain the appropriate dose in infants, young pediatric patients, or patients with very low body weight.
For adults and pediatric patients if a loading dosage is to be given, administer half the total loading dose initially, then ¼ the loading dose every 6 to 8 hours twice, with careful assessment of clinical response and toxicity before each dose. The recommended loading dose is displayed in Table 1.
Table 1. Recommended Digoxin Tablets Oral Loading Dose Age Total Oral Loading Dose (mcg/kg)
Administer half the total loading dose initially, then ¼ the loading dose every 6 to 8 hours twice 5 to 10 years 20 to 45 Adults and pediatric patients over 10 years 10 to 15The maintenance dose is based on lean body weight, renal function, age, and concomitant products [see Clinical Pharmacology (12.3)].
The recommended starting maintenance dose in adults and pediatric patients over 10 years old with normal renal function is given in Table 2. Doses may be increased every 2 weeks according to clinical response, serum drug levels, and toxicity.
Table 2. Recommended Starting Digoxin Tablets Maintenance Dosage in Adults and Pediatric Patients Over 10 Years Old Age Total Oral Maintenance Dose, mcg/kg/day (given once daily) Adults and pediatric patients over 10 years 3.4 to 5.1Table 3 provides the recommended (once daily) maintenance dose for adults and pediatric patients over 10 years old (to be given once daily) according to lean body weight and renal function. The doses are based on studies in adult patients with heart failure. Alternatively, the maintenance dose may be estimated by the following formula (peak body stores lost each day through elimination):
Total Maintenance Dose = Loading Dose (i.e., Peak Body Stores) × % Daily Loss/100
(% Daily Loss = 14 + Creatinine clearance/5)Reduce the dose of digoxin tablets in patients whose lean weight is an abnormally small fraction of their total body mass because of obesity or edema.
Table 3. Recommended Maintenance Dose (in micrograms given once daily) of Digoxin Tablets in Pediatric Patients Over 10 Years Old and Adults by Lean Body Weight and by Renal Function* Corrected Creatinine Clearance† Lean Body Weight‡ Number of Days Before Steady State Achieved§ kg 40 50 60 70 80 90 100 10 mL/min 62.5* 125 125 187.5 187.5 187.5 250 19 20 mL/min 125 125 125 187.5 187.5 250 250 16 30 mL/min 125 125 187.5 187.5 250 250 312.5 14 40 mL/min 125 187.5 187.5 250 250 312.5 312.5 13 50 mL/min 125 187.5 187.5 250 250 312.5 312.5 12 60 mL/min 125 187.5 250 250 312.5 312.5 375 11 70 mL/min 187.5 187.5 250 250 312.5 375 375 10 80 mL/min 187.5 187.5 250 312.5 312.5 375 437.5 9 90 mL/min 187.5 250 250 312.5 375 437.5 437.5 8 100 mL/min 187.5 250 312.5 312.5 375 437.5 500 71
2
3
4
The starting maintenance dose for heart failure in pediatric patients less than 10 years old is based on lean body weight, renal function, age, and concomitant products [see Clinical Pharmacology (12.3)]. The recommended starting maintenance dose for pediatric patients between 5 years and 10 years old is given in Table 4. These recommendations assume the presence of normal renal function.
Table 4. Recommended Starting Digoxin Tablets Oral Maintenance Dosage in Pediatric Patients between 5 and 10 Years Old Age Oral Maintenance Dose, mcg/kg/dose 5 years to 10 years 3.2 to 6.4 Twice dailyTable 5 provides average daily maintenance dose requirements for pediatric patients between 5 and 10 years old (to be given twice daily) with heart failure based on age, lean body weight, and renal function.
Table 5. Recommended Maintenance Dose (in micrograms given TWICE daily) of Digoxin Tablets in Pediatric Patients between 5 and 10 Years of Agea Based upon Lean Body Weight and Renal Function*,† Corrected Creatinine Clearance‡ Lean Body Weight Number of Days Before Steady State Achieved§ kg 20 30 40 50 60 10 mL/min - 62.5 62.5* 125 125 19 20 mL/min 62.5 62.5 125 125 125 16 30 mL/min 62.5 62.5* 125 125 187.5 14 40 mL/min 62.5 62.5* 125 187.5 187.5 13 50 mL/min 62.5 125 125 187.5 187.5 12 60 mL/min 62.5 125 125 187.5 250 11 70 mL/min 62.5 125 187.5 187.5 250 10 80 mL/min 62.5* 125 187.5 187.5 250 9 90 mL/min 62.5* 125 187.5 250 250 8 100 mL/min 62.5* 125 187.5 250 312.5 75
6
7
8
Monitor for signs and symptoms of digoxin toxicity and clinical response. Adjust dose based on toxicity, efficacy, and blood levels.
Serum digoxin levels less than 0.5 ng/mL have been associated with diminished efficacy, while levels above 2 ng/mL have been associated with increased toxicity without increased benefit.
Interpret the serum digoxin concentration in the overall clinical context, and do not use an isolated measurement of serum digoxin concentration as the basis for increasing or decreasing the digoxin tablets dose. Serum digoxin concentrations may be falsely elevated by endogenous digoxin-like substances [see Drug Interactions (7.4)]. If the assay is sensitive to these substances, consider obtaining a baseline digoxin level before starting digoxin tablets and correct post-treatment values by the reported baseline level.
Obtain serum digoxin concentrations just before the next scheduled digoxin tablets dose or at least 6 hours after the last dose. The digoxin concentration is likely to be 10 to 25% lower when sampled right before the next dose (24 hours after dosing) compared to sampling 8 hours after dosing (using once-daily dosing). However, there will be only minor differences in digoxin concentrations using twice daily dosing whether sampling is done at 8 or 12 hours after a dose.
When switching from intravenous to oral digoxin formulations, make allowances for differences in bioavailability when calculating maintenance dosages (see Table 6).
Table 6. Comparison of the Systemic Availability and Equivalent Doses of Oral and Intravenous Digoxin Tablets Absolute Bioavailability Equivalent Doses (mcg) Digoxin Tablets 60 to 80% 62.5 125 250 500 Digoxin Intravenous Injection 100% 50 100 200 400
1 Doses are rounded to the nearest dose possible using whole and/or half digoxin tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed. 2 , creatinine clearance was corrected to 70-kg body weight or 1.73 m 3 The doses listed assume average body composition. 4 If no loading dose administered. 5 Recommended are doses to be given twice daily. 6 The doses are rounded to the nearest dose possible using whole and/or half digoxin tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed. 7 The modified Schwartz equation may be used to estimate creatinine clearance. See 8 If no loading dose administered. -
Cardinal Health
Digoxin | Cardinal Health
GeneralRecommended 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:
The body weight of the patient. Doses should be calculated based upon lean (i.e., ideal) body weight. The patient's renal function, preferably evaluated on the basis of estimated creatinine clearance. 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). Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharmacodynamic profile of digoxin (see PRECAUTIONS). Serum Digoxin ConcentrationsIn 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:
Analytical problems in the assay procedure. Inappropriate serum sampling time. Administration of a digitalis glycoside other than digoxin. Conditions (described in WARNINGS and PRECAUTIONS) causing an alteration in the sensitivity of the patient to digoxin. 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 AdultsDigitalization 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.
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. 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 DosePeak 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 DosingThe 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* Corrected Ccr kg 50 60 70 80 90 100 (mL/min per 70 kg)† lb 110 132 154 176 198 220 * If no loading dose administered. † Ccr is creatinine clearance, corrected to 70-kg body weight or 1.73 m 2 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. ‡ 62.5 mcg = 0.0625 mg 0 62.5‡ 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 7Example: 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 ChildrenIn 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 5In 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 FibrillationPeak 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 PreparationsThe difference in bioavailability between digoxin injection or digoxin tablets must be considered when changing patients from one dosage form to the other.
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West-ward Pharmaceutical Corp.
Digoxin | Hospira, Inc.
2.1 Dosing Guidelines • Precedex dosing should be individualized and titrated to desired clinical response. • Precedex is not indicated for infusions lasting longer than 24 hours. • Precedex should be administered using a controlled infusion device. 2.2 Dosage Information Table 1: Dosage InformationINDICATION
DOSAGE AND ADMINISTRATION
Initiation of Intensive Care Unit Sedation
For adult patients: a loading infusion of one mcg/kg over 10 minutes.
For adult patients being converted from alternate sedative therapy: a loading dose may not be required [see Dosage and Administration (2.2)].
For patients over 65 years of age: a dose reduction should be considered [see Use in Specific Populations (8.5)].
For adult patients with impaired hepatic-function: a dose reduction should be considered [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
Maintenance of Intensive Care Unit Sedation
For adult patients: a maintenance infusion of 0.2 to 0.7 mcg/kg/hour. The rate of the maintenance infusion should be adjusted to achieve the desired level of sedation.
For patients over 65 years of age: a dose reduction should be considered [see Use in Specific Populations (8.5)].
For adult patients with impaired hepatic function: a dose reduction should be considered [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
Initiation of Procedural Sedation
For adult patients: a loading infusion of one mcg/kg over 10 minutes. For less invasive procedures such as ophthalmic surgery, a loading infusion of 0.5 mcg/kg given over 10 minutes may be suitable.
For awake fiberoptic intubation in adult patients: a loading infusion of one mcg/kg over 10 minutes.
For patients over 65 years of age: a loading infusion of 0.5 mcg/kg over 10 minutes [see Use in Specific Populations (8.5)].
For adult patients with impaired hepatic function: a dose reduction should be considered [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
Maintenance of Procedural Sedation
For adult patients: the maintenance infusion is generally initiated at 0.6 mcg/kg/hour and titrated to achieve desired clinical effect with doses ranging from 0.2 to 1 mcg/kg/hour. The rate of the maintenance infusion should be adjusted to achieve the targeted level of sedation.
For awake fiberoptic intubation in adult patients: a maintenance infusion of 0.7 mcg/kg/hour is recommended until the endotracheal tube is secured.
For patients over 65 years of age: a dose reduction should be considered [see Use in Specific Populations (8.5)].
For adult patients with impaired hepatic function: a dose reduction should be considered [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
2.3 Dosage AdjustmentDue to possible pharmacodynamic interactions, a reduction in dosage of Precedex or other concomitant anesthetics, sedatives, hypnotics or opioids may be required when co-administered [see Drug Interactions (7.1)].
Dosage reductions may need to be considered for adult patients with hepatic impairment, and geriatric patients [see Warnings and Precautions (5.7), Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
2.4 Preparation of SolutionStrict aseptic technique must always be maintained during handling of Precedex.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Precedex Injection, 200 mcg/2 mL (100 mcg/mL)
Precedex must be diluted with 0.9% sodium chloride injection to achieve required concentration (4 mcg/mL) prior to administration. Preparation of solutions is the same, whether for the loading dose or maintenance infusion.
To prepare the infusion, withdraw 2 mL of Precedex Injection, and add to 48 mL of 0.9% sodium chloride injection to a total of 50 mL. Shake gently to mix well.
Precedex in 0.9% Sodium Chloride Injection, 80 mcg/20 mL (4 mcg/mL), 200 mcg/50 mL (4 mcg/mL) and 400 mcg/100 mL (4 mcg/mL)
Precedex in 0.9% Sodium Chloride Injection is supplied in glass containers containing a premixed, ready to use dexmedetomidine hydrochloride solution in 0.9% sodium chloride in water. No further dilution of these preparations are necessary.
2.5 Administration with Other FluidsPrecedex infusion should not be co-administered through the same intravenous catheter with blood or plasma because physical compatibility has not been established.
Precedex has been shown to be incompatible when administered with the following drugs: amphotericin B, diazepam.
Precedex has been shown to be compatible when administered with the following intravenous fluids:
• 0.9% sodium chloride in water • 5% dextrose in water • 20% mannitol • Lactated Ringer’s solution • 100 mg/mL magnesium sulfate solution • 0.3% potassium chloride solution 2.6 Compatibility with Natural RubberCompatibility studies have demonstrated the potential for absorption of Precedex to some types of natural rubber. Although Precedex is dosed to effect, it is advisable to use administration components made with synthetic or coated natural rubber gaskets.
2.1 Dosing Guidelines • Precedex dosing should be individualized and titrated to desired clinical response. • Precedex is not indicated for infusions lasting longer than 24 hours. • Precedex should be administered using a controlled infusion device. 2.2 Dosage Information Table 1: Dosage InformationINDICATION
DOSAGE AND ADMINISTRATION
Initiation of Intensive Care Unit Sedation
For adult patients: a loading infusion of one mcg/kg over 10 minutes.
For adult patients being converted from alternate sedative therapy: a loading dose may not be required [see Dosage and Administration (2.2)].
For patients over 65 years of age: a dose reduction should be considered [see Use in Specific Populations (8.5)].
For adult patients with impaired hepatic-function: a dose reduction should be considered [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
Maintenance of Intensive Care Unit Sedation
For adult patients: a maintenance infusion of 0.2 to 0.7 mcg/kg/hour. The rate of the maintenance infusion should be adjusted to achieve the desired level of sedation.
For patients over 65 years of age: a dose reduction should be considered [see Use in Specific Populations (8.5)].
For adult patients with impaired hepatic function: a dose reduction should be considered [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
Initiation of Procedural Sedation
For adult patients: a loading infusion of one mcg/kg over 10 minutes. For less invasive procedures such as ophthalmic surgery, a loading infusion of 0.5 mcg/kg given over 10 minutes may be suitable.
For awake fiberoptic intubation in adult patients: a loading infusion of one mcg/kg over 10 minutes.
For patients over 65 years of age: a loading infusion of 0.5 mcg/kg over 10 minutes [see Use in Specific Populations (8.5)].
For adult patients with impaired hepatic function: a dose reduction should be considered [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
Maintenance of Procedural Sedation
For adult patients: the maintenance infusion is generally initiated at 0.6 mcg/kg/hour and titrated to achieve desired clinical effect with doses ranging from 0.2 to 1 mcg/kg/hour. The rate of the maintenance infusion should be adjusted to achieve the targeted level of sedation.
For awake fiberoptic intubation in adult patients: a maintenance infusion of 0.7 mcg/kg/hour is recommended until the endotracheal tube is secured.
For patients over 65 years of age: a dose reduction should be considered [see Use in Specific Populations (8.5)].
For adult patients with impaired hepatic function: a dose reduction should be considered [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
2.3 Dosage AdjustmentDue to possible pharmacodynamic interactions, a reduction in dosage of Precedex or other concomitant anesthetics, sedatives, hypnotics or opioids may be required when co-administered [see Drug Interactions (7.1)].
Dosage reductions may need to be considered for adult patients with hepatic impairment, and geriatric patients [see Warnings and Precautions (5.7), Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
2.4 Preparation of SolutionStrict aseptic technique must always be maintained during handling of Precedex.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Precedex Injection, 200 mcg/2 mL (100 mcg/mL)
Precedex must be diluted with 0.9% sodium chloride injection to achieve required concentration (4 mcg/mL) prior to administration. Preparation of solutions is the same, whether for the loading dose or maintenance infusion.
To prepare the infusion, withdraw 2 mL of Precedex Injection, and add to 48 mL of 0.9% sodium chloride injection to a total of 50 mL. Shake gently to mix well.
Precedex in 0.9% Sodium Chloride Injection, 80 mcg/20 mL (4 mcg/mL), 200 mcg/50 mL (4 mcg/mL) and 400 mcg/100 mL (4 mcg/mL)
Precedex in 0.9% Sodium Chloride Injection is supplied in glass containers containing a premixed, ready to use dexmedetomidine hydrochloride solution in 0.9% sodium chloride in water. No further dilution of these preparations are necessary.
2.5 Administration with Other FluidsPrecedex infusion should not be co-administered through the same intravenous catheter with blood or plasma because physical compatibility has not been established.
Precedex has been shown to be incompatible when administered with the following drugs: amphotericin B, diazepam.
Precedex has been shown to be compatible when administered with the following intravenous fluids:
• 0.9% sodium chloride in water • 5% dextrose in water • 20% mannitol • Lactated Ringer’s solution • 100 mg/mL magnesium sulfate solution • 0.3% potassium chloride solution 2.6 Compatibility with Natural RubberCompatibility studies have demonstrated the potential for absorption of Precedex to some types of natural rubber. Although Precedex is dosed to effect, it is advisable to use administration components made with synthetic or coated natural rubber gaskets.
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Sandoz Inc
Digoxin | C & C Oxygen Company
There is currently no dosage information available for this product. We apologize for any inconvenience.
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State Of Florida Doh Central Pharmacy
Digoxin | State Of Florida Doh Central Pharmacy
GeneralRecommended 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:
The body weight of the patient. Doses should be calculated based upon lean (i.e., ideal) body weight. The patient's renal function, preferably evaluated on the basis of estimated creatinine clearance. 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). Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharmacodynamic profile of digoxin (see PRECAUTIONS). Serum Digoxin ConcentrationsIn 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:
Analytical problems in the assay procedure. Inappropriate serum sampling time. Administration of a digitalis glycoside other than digoxin. Conditions (described in WARNINGS and PRECAUTIONS) causing an alteration in the sensitivity of the patient to digoxin. 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 AdultsDigitalization 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.
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. 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 DosePeak 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 DosingThe 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* Corrected Ccr kg 50 60 70 80 90 100 (mL/min per 70 kg)† lb 110 132 154 176 198 220 * If no loading dose administered. † Ccr is creatinine clearance, corrected to 70-kg body weight or 1.73 m 2 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. ‡ 62.5 mcg = 0.0625 mg 0 62.5‡ 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 7Example: 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 ChildrenIn 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 5In 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 FibrillationPeak 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 PreparationsThe difference in bioavailability between digoxin injection or digoxin tablets must be considered when changing patients from one dosage form to the other.
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Northwind Pharmaceuticals
Digoxin | Northwind Pharmaceuticals
There is currently no dosage information available for this product. We apologize for any inconvenience.
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Northwind Pharmaceuticals
Digoxin | Northwind Pharmaceuticals
There is currently no dosage information available for this product. We apologize for any inconvenience.
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Bryant Ranch Prepack
Digoxin | Bryant Ranch Prepack
GeneralRecommended 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:
The body weight of the patient. Doses should be calculated based upon lean (i.e., ideal) body weight. The patient's renal function, preferably evaluated on the basis of estimated creatinine clearance. 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). Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharmacodynamic profile of digoxin (see PRECAUTIONS). Serum Digoxin ConcentrationsIn 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 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 ng/mL. However, since one-third of patients with clinical toxicity have concentrations less than 2 ng/mL, values below 2 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:
Analytical problems in the assay procedure. Inappropriate serum sampling time. Administration of a digitalis glycoside other than digoxin. Conditions (described in WARNINGS and PRECAUTIONS) causing an alteration in the sensitivity of the patient to digoxin. 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: AdultsDigitalization 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.
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. 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 five 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 DosePeak 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 1250 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 DosingThe 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 1800 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) x % 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 Tablets for Estimated Peak Body Stores of 10 mcg/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.
† lf no loading dose administered.
‡ 62.5 mcg = 0.0625 mg
Corrected Ccr Lean Body Weight Number of (mL/min kg 50 60 70 80 90 100 Days Before per 70 kg)* lb 110 132 154 176 198 220 Steady State Achieved† 0 62.5‡ 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 ExampleBased 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 ChildrenIn 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 5In 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 FibrillationPeak 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 PreparationsThe difference in bioavailability between Digoxin Injection or Digoxin 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 digoxin solution in capsules are approximately equivalent to 125 mcg (0.125 mg) and 250 mcg (0.25 mg) doses of digoxin tablets and digoxin pediatric elixir, respectively (see Table 1 in CLINICAL PHARMACOLOGY: Pharmacokinetics).
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West-ward Pharmaceutical Corp
Digoxin | West-ward Pharmaceutical Corp
2.1 Important Dosing and Administration InformationIn selecting a Digoxin Tablets dosing regimen, it is important to consider factors that affect digoxin blood levels (e.g., body weight, age, renal function, concomitant drugs) since toxic levels of digoxin are only slightly higher than therapeutic levels. Dosing can be either initiated with a loading dose followed by maintenance dosing if rapid titration is desired or initiated with maintenance dosing without a loading dose.
Consider interruption or reduction in Digoxin Tablets dose prior to electrical cardioversion [see Warnings and Precautions (5.4)].
Use digoxin solution to obtain the appropriate dose in infants, young pediatric patients, or patients with very low body weight.
2.2 Loading Dosing Regimen in Adults and Pediatric PatientsFor adults and pediatric patients if a loading dosage is to be given, administer half the total loading dose initially, then ¼ the loading dose every 6 to 8 hours twice, with careful assessment of clinical response and toxicity before each dose. The recommended loading dose is displayed in Table 1.
Table 1. Recommended Digoxin Tablets Oral Loading Dose mcg = microgram Age Total Oral Loading Dose (mcg/kg)Administer half the total loading dose initially,
5 to 10 years 20 to 45 Adults and pediatric patients over 10 years 10 to 15 2.3 Maintenance Dosing in Adults and Pediatric Patients Over 10 Years Old
then ¼ the loading dose every 6 to 8 hours twiceThe maintenance dose is based on lean body weight, renal function, age, and concomitant products [see Clinical Pharmacology(12.3)].
The recommended starting maintenance dose in adults and pediatric patients over 10 years old with normal renal function is given in Table 2. Doses may be increased every 2 weeks according to clinical response, serum drug levels, and toxicity.
Table 2. Recommended Starting Digoxin Tablets Maintenance Dosage in Adults and Pediatric Patients Over 10 Years Old mcg = microgram Age Total Oral Maintenance Dose, mcg/kg/day
(given once daily) Adults and pediatric patients over 10 years 3.4 to 5.1Table 3 provides the recommended (once daily) maintenance dose for adults and pediatric patients over 10 years old (to be given once daily) according to lean body weight and renal function. The doses are based on studies in adult patients with heart failure. Alternatively, the maintenance dose may be estimated by the following formula (peak body stores lost each day through elimination):
Total Maintenance Dose = Loading Dose (i.e., Peak Body Stores) x % Daily Loss/100
(% Daily Loss = 14 + Creatinine clearance/5)Reduce the dose of Digoxin Tablets in patients whose lean weight is an abnormally small fraction of their total body mass because of obesity or edema.
Table 3. Recommended Maintenance Dose (in micrograms given once daily) of Digoxin Tablets in Pediatric Patients Over 10 Years Old and Adults by Lean Body Weight and by Renal Functiona a Doses are rounded to the nearest dose possible using whole and/or half digoxin tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed.
b For adults, creatinine clearance was corrected to 70-kg body weight or 1.73 m2body surface area. If only serum creatinine concentrations (Scr) are available, a corrected Ccr may be estimated in men as (140 – Age)/Scr. For women, this result should be multiplied by 0.85.
For pediatric patients, the modified Schwartz equation may be used. The formula is based on height in cm and Scr in mg/dL where k is a constant. Ccr is corrected to 1.73 m2 body surface area. During the first year of life, the value of k is 0.33 for pre-term babies and 0.45 for term infants. The k is 0.55 for pediatric patients and adolescent girls and 0.7 for adolescent boys.
GFR (mL/min/1.73 m2) = (k x Height)/Scr
c If no loading dose administered.
d The doses listed assume average body composition. Corrected
Creatinine
Clearanceb Lean Body Weightd Number of Days
Before Steady
State Achievedc kg 40 50 60 70 80 90 100 10 mL/min 62.5* 125 125 187.5 187.5 187.5 250 19 20 mL/min 125 125 125 187.5 187.5 250 250 16 30 mL/min 125 125 187.5 187.5 250 250 312.5 14 40 mL/min 125 187.5 187.5 250 250 312.5 312.5 13 50 mL/min 125 187.5 187.5 250 250 312.5 312.5 12 60 mL/min 125 187.5 250 250 312.5 312.5 375 11 70 mL/min 187.5 187.5 250 250 312.5 375 375 10 80 mL/min 187.5 187.5 250 312.5 312.5 375 437.5 9 90 mL/min 187.5 250 250 312.5 375 437.5 437.5 8 100 mL/min 187.5 250 312.5 312.5 375 437.5 500 7 2.4 Maintenance Dosing in Pediatric Patients Less Than 10 Years OldThe starting maintenance dose for heart failure in pediatric patients less than 10 years old is based on lean body weight, renal function, age, and concomitant products [see Clinical Pharmacology (12.3)]. The recommended starting maintenance dose for pediatric patients between 5 years and 10 years old is given in Table 4. These recommendations assume the presence of normal renal function.
Table 4. Recommended Starting Digoxin Tablets Oral Maintenance Dosage in Pediatric Patients between 5 and 10 Years Old Age Oral Maintenance Dose,
mcg/kg/dose 5 years to 10 years 3.2 to 6.4 Twice dailyTable 5 provides average daily maintenance dose requirements for pediatric patients between 5 and 10 years old (to be given twice daily) with heart failure based on age, lean body weight, and renal function.
Table 5. Recommended Maintenance Dose (in micrograms given TWICE daily) of Digoxin Tablets in Pediatric Patients between 5 and 10 Years of Agea Based upon Lean Body Weight and Renal Functiona,ba Recommended are doses to be given twice daily.
Corrected
b The doses are rounded to the nearest dose possible using whole and/or half digoxin tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed.
c The modified Schwartz equation may be used to estimate creatinine clearance. See footnote b under Table 3.
d If no loading dose administered.
Creatinine
Clearancec Lean Body Weight Number of Days
Before Steady
State Achievedd kg 20 30 40 50 60 10 mL/min - 62.5 62.5* 125 125 19 20 mL/min 62.5 2.5 125 125 125 16 30 mL/min 62.5 62.5* 125 125 187.5 14 40 mL/min 62.5 62.5* 125 187.5 187.5 13 50 mL/min 62.5 125 125 187.5 187.5 12 60 mL/min 62.5 125 125 187.5 250 11 70 mL/min 62.5 125 187.5 187.5 250 10 80 mL/min 62.5* 125 187.5 187.5 250 9 90 mL/min 62.5* 125 187.5 250 250 8 100 mL/min 62.5* 125 187.5 250 312.5 7 2.5 Monitoring to Assess Safety, Efficacy, and Therapeutic Blood LevelsMonitor for signs and symptoms of digoxin toxicity and clinical response. Adjust dose based on toxicity, efficacy, and blood levels.
Serum digoxin levels less than 0.5 ng/mL have been associated with diminished efficacy, while levels above 2 ng/mL have been associated with increased toxicity without increased benefit.
Interpret the serum digoxin concentration in the overall clinical context, and do not use an isolated measurement of serum digoxin concentration as the basis for increasing or decreasing the Digoxin Tablets dose. Serum digoxin concentrations may be falsely elevated by endogenous digoxin-like substances [see Drug Interactions (7.4)]. If the assay is sensitive to these substances, consider obtaining a baseline digoxin level before starting Digoxin Tablets and correct post-treatment values by the reported baseline level.
Obtain serum digoxin concentrations just before the next scheduled Digoxin Tablets dose or at least
6 hours after the last dose. The digoxin concentration is likely to be 10 to 25% lower when sampled right before the next dose (24 hours after dosing) compared to sampling 8 hours after dosing (using once-daily dosing). However, there will be only minor differences in digoxin concentrations using twice daily dosing whether sampling is done at 8 or 12 hours after a dose.
2.6 Switching from Intravenous Digoxin to Oral DigoxinWhen switching from intravenous to oral digoxin formulations, make allowances for differences in bioavailability when calculating maintenance dosages (see Table 6).
Table 6. Comparison of the Systemic Availability and Equivalent Doses of Oral and Intravenous Digoxin Absolute
Bioavailability Equivalent Doses (mcg) Digoxin Tablets 60-80% 62.5 125 250 500 Digoxin Intravenous Injection 100% 50 100 200 400 -
Cardinal Health
Digoxin | Cardinal Health
2.1 Important Dosing and Administration InformationIn selecting a digoxin dosing regimen, it is important to consider factors that affect digoxin blood levels (e.g., body weight, age, renal function, concomitant drugs) since toxic levels of digoxin are only slightly higher than therapeutic levels. Dosing can be either initiated with a loading dose followed by maintenance dosing if rapid titration is desired or initiated with maintenance dosing without a loading dose.
Parenteral administration of digoxin should be used only when the need for rapid digitalization is urgent or when the drug cannot be taken orally. Intramuscular injection can lead to severe pain at the injection site, thus intravenous administration is preferred. If the drug must be administered by the intramuscular route, it should be injected deep into the muscle followed by massage. For adults, no more than 500 mcg of Digoxin Injection should be injected into a single site. For pediatric patients, see the full prescribing information for pediatric digoxin injection (not available from West-Ward) for specific recommendations.
Administer the dose over a period of 5 minutes or longer and avoid bolus administration to prevent systemic and coronary vasoconstriction. Mixing of Digoxin Injection with other drugs in the same container or simultaneous administration in the same intravenous line is not recommended.
Digoxin Injection can be administered undiluted or diluted with a 4-fold or greater volume of Sterile Water for Injection, 0.9% Sodium Chloride Injection, or 5% Dextrose Injection. The use of less than a 4-fold volume of diluent could lead to precipitation of the digoxin. Immediate use of the diluted product is recommended.
If tuberculin syringes are used to measure very small doses do not flush with the parenteral solution after its contents are expelled into an indwelling vascular catheter to avoid over administration of digoxin.
Consider interruption or reduction in digoxin dose prior to electrical cardioversion [see Warnings and Precautions (5.4)].
2.2 Loading Dosing Regimen in Adult Patients Table 1. Recommended Digoxin Injection Loading Dose mcg = microgramAge
Total IV Loading Dose (mcg/kg)
Administer half the total loading dose initially,
then ¼ the loading dose every 6-8 hours twiceAdult patients
8-12
2.3 Maintenance Dosing in Adult PatientsThe maintenance dose is based on lean body weight, renal function, age, and concomitant products [see Clinical Pharmacology (12.3)].
The recommended starting maintenance dose in adults patients with normal renal function is given in Table 2. Doses may be increased every 2 weeks according to clinical response, serum drug levels, and toxicity.
Table 2. Recommended Starting Digoxin Injection Maintenance Dosage in Adult Patients mcg = microgramAge
Total Intravenous Maintenance Dose,
mcg/kg/day
(given once daily)Adult patients
2.4-3.6
Table 3 provides the recommended (once daily) maintenance dose for adult patients according to lean body weight and renal function. The doses are based on studies in adult patients with heart failure. Alternatively, the maintenance dose may be estimated by the following formula (peak body stores lost each day through elimination):
Total Maintenance Dose = Loading Dose (i.e., Peak Body Stores) x % Daily Loss/100
(% Daily Loss = 14 + Creatinine clearance/5)Reduce the dose of digoxin in patients whose lean weight is an abnormally small fraction of their total body mass because of obesity or edema.
Table 3. Recommended Maintenance Dose (in micrograms given once daily) of Digoxin Injection in Adult Patients by Lean Body Weight and by Renal Function a For adults, creatinine clearance was corrected to 70-kg body weight or 1.73 m2 body surface area. If only serum creatinine concentrations (Scr) are available, a corrected Ccr may be estimated in men as (140 – Age)/Scr. For women, this result should be multiplied by 0.85.
GFR (mL/min/1.73 m2) = (k x Height)/Scr
b If no loading dose administered
c The doses listed assume average body composition.Corrected
Creatinine ClearanceaLean Body Weightc
Number of Days
Before Steady
State Achievedbkg
40
50
60
70
80
90
100
10 mL/min
64
80
96
112
128
144
160
19
20 mL/min
72
90
108
126
144
162
180
16
30 mL/min
80
100
120
140
160
180
200
14
40 mL/min
88
110
132
154
176
198
220
13
50 mL/min
96
120
144
168
192
216
240
12
60 mL/min
104
130
156
182
208
234
260
11
70 mL/min
112
140
168
196
224
252
280
10
80 mL/min
120
150
180
210
240
270
300
9
90 mL/min
128
160
192
224
256
288
320
8
100 mL/min
136
170
204
238
272
306
340
7
2.4 Monitoring to Assess Safety, Efficacy, and Therapeutic Blood LevelsMonitor for signs and symptoms of digoxin toxicity and clinical response. Adjust dose based on toxicity, efficacy, and blood levels.
Serum digoxin levels less than 0.5 ng/mL have been associated with diminished efficacy, while levels above 2 ng/mL have been associated with increased toxicity without increased benefit.
Interpret the serum digoxin concentration in the overall clinical context, and do not use an isolated measurement of serum digoxin concentration as the basis for increasing or decreasing the digoxin dose. Serum digoxin concentrations may be falsely elevated by endogenous digoxin-like substances [see Drug Interactions (7.4)]. If the assay is sensitive to these substances, consider obtaining a baseline digoxin level before starting digoxin and correct post-treatment values by the reported baseline level.
Obtain serum digoxin concentrations just before the next scheduled digoxin dose or at least 6 hours after the last dose. The digoxin concentration is likely to be 10-25% lower when sampled right before the next dose (24 hours after dosing) compared to sampling 8 hours after dosing (using once-daily dosing). However, there will be only minor differences in digoxin concentrations using twice daily dosing whether sampling is done at 8 or 12 hours after a dose.
2.5 Switching from Intravenous Digoxin to Oral DigoxinWhen switching from intravenous to oral digoxin formulations, make allowances for differences in bioavailability when calculating maintenance dosages (see Table 4).
Table 4. Comparison of the Systemic Availability and Equivalent Doses of Oral and Intravenous DigoxinAbsolute Bioavailability
Equivalent Doses (mcg)
Digoxin Tablets
60-80%
62.5
125
250
500
Digoxin Intravenous Injection
100%
50
100
200
400
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Cardinal Health
Digoxin | Cardinal Health
2.1 Important Dosing and Administration InformationIn selecting a DIGOXIN dosing regimen, it is important to consider factors that affect digoxin blood levels (e.g., body weight, age, renal function, concomitant drugs) since toxic levels of digoxin are only slightly higher than therapeutic levels. Dosing can be either initiated with a loading dose followed by maintenance dosing if rapid titration is desired or initiated with maintenance dosing without a loading dose.
Consider interruption or reduction in DIGOXIN digoxin dose prior to electrical cardioversion [see Warnings and Precautions (5.4)].
Use digoxin solution to obtain the appropriate dose in infants, young pediatric patients, or patients with very low body weight.
2.2 Loading Dosing Regimen in Adults and Pediatric PatientsFor adults and pediatric patients if a loading dosage is to be given, administer half the total loading dose initially, then ¼ the loading dose every 6-8 hours twice, with careful assessment of clinical response and toxicity before each dose. The recommended loading dose is displayed in Table 1.
Table 1. Recommended DIGOXIN Oral Loading Dose mcg = microgramAge
Total Oral Loading Dose (mcg/kg)
Administer half the total loading dose initially,
then ¼ the loading dose every 6 to 8 hours twice5 to 10 years
20-45
Adults and pediatric patients over 10 years
10-15
2.3 Maintenance Dosing in Adults and Pediatric Patients Over 10 Years OldThe maintenance dose is based on lean body weight, renal function, age, and concomitant products [see Clinical Pharmacology (12.3)].
The recommended starting maintenance dose in adults and pediatric patients over 10 years old with normal renal function is given in Table 2. Doses may be increased every 2 weeks according to clinical response, serum drug levels, and toxicity.
Table 2. Recommended Starting DIGOXIN Maintenance Dosage in Adults and Pediatric Patients Over 10 Years Old mcg = microgramAge
Total Oral Maintenance Dose, mcg/kg/day
(given once daily)Adults and pediatric patients over 10 years
3.4-5.1
Table 3 provides the recommended (once daily) maintenance dose for adults and pediatric patients over 10 years old (to be given once daily) according to lean body weight and renal function. The doses are based on studies in adult patients with heart failure. Alternatively, the maintenance dose may be estimated by the following formula (peak body stores lost each day through elimination):
Total Maintenance Dose = Loading Dose (i.e., Peak Body Stores) x % Daily Loss/100
(% Daily Loss = 14 + Creatinine clearance/5)Reduce the dose of DIGOXIN in patients whose lean weight is an abnormally small fraction of their total body mass because of obesity or edema.
Table 3. Recommended Maintenance Dose (in micrograms given once daily) of DIGOXIN in Pediatric Patients Over 10 Years Old and Adults by Lean Body Weight and by Renal Functiona a Doses are rounded to the nearest dose possible using whole DIGOXIN tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed.
b For adults, creatinine clearance was corrected to 70-kg body weight or 1.73 m2 body surface area. If only serum creatinine concentrations (Scr) are available, a corrected Ccr may be estimated in men as (140 – Age)/Scr. For women, this result should be multiplied by 0.85.
For pediatric patients, the modified Schwartz equation may be used. The formula is based on height in cm and Scr in mg/dL where k is a constant. Ccr is corrected to 1.73 m2 body surface area. During the first year of life, the value of k is 0.33 for pre-term babies and 0.45 for term infants. The k is 0.55 for pediatric patients and adolescent girls and 0.7 for adolescent boys.
GFR (mL/min/1.73 m2) = (k x Height)/Scr
c If no loading dose administered.
d The doses listed assume average body composition.Corrected
Creatinine
ClearancebLean Body Weightd
Number of Days
Before Steady
State Achievedckg
40
50
60
70
80
90
100
10 mL/min 62.5* 125 125 187.5 187.5 187.5 250 19 20 mL/min 125 125 125 187.5 187.5 250 250 16 30 mL/min 125 125 187.5 187.5 250 250 312.5 14 40 mL/min 125 187.5 187.5 250 250 312.5 312.5 13 50 mL/min 125 187.5 187.5 250 250 312.5 312.5 12 60 mL/min 125 187.5 250 250 312.5 312.5 375 11 70 mL/min 187.5 187.5 250 250 312.5 375 375 10 80 mL/min 187.5 187.5 250 312.5 312.5 375 437.5 9 90 mL/min 187.5 250 250 312.5 375 437.5 437.5 8 100 mL/min 187.5 250 312.5 312.5 375 437.5 500 7 2.4 Maintenance Dosing in Pediatric Patients Less Than 10 Years OldThe starting maintenance dose for heart failure in pediatric patients less than 10 years old is based on lean body weight, renal function, age, and concomitant products [see Clinical Pharmacology (12.3)]. The recommended starting maintenance dose for pediatric patients between 5 years and 10 years old is given in Table 4. These recommendations assume the presence of normal renal function.
Table 4. Recommended Starting DIGOXIN Oral Maintenance Dosage in Pediatric Patients between 5 and 10 Years OldAge
Oral Maintenance Dose,
mcg/kg/dose5 years to 10 years
3.2-6.4 Twice daily
Table 5 provides average daily maintenance dose requirements for pediatric patients between 5 and 10 years old (to be given twice daily) with heart failure based on age, lean body weight, and renal function.
Table 5. Recommended Maintenance Dose (in micrograms given TWICE daily) of DIGOXIN in Pediatric Patients between 5 and 10 Years of Agea Based upon Lean Body Weight and Renal Functiona,b a Recommended are doses to be given twice daily.
b The doses are rounded to the nearest dose possible using whole DIGOXIN tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed.
c The modified Schwartz equation may be used to estimate creatinine clearance. See footnote b under Table 3.
d If no loading dose administered.Corrected
Creatinine
ClearancecLean Body Weight
Number of Days
Before Steady
State Achieveddkg
20
30
40
50
60
10 mL/min - 62.5 62.5* 125 125 19 20 mL/min 62.5 62.5 125 125 125 16 30 mL/min 62.5 62.5* 125 125 187.5 14 40 mL/min 62.5 62.5* 125 187.5 187.5 13 50 mL/min 62.5 125 125 187.5 187.5 12 60 mL/min 62.5 125 125 187.5 250 11 70 mL/min 62.5 125 187.5 187.5 250 10 80 mL/min 62.5* 125 187.5 187.5 250 9 90 mL/min 62.5* 125 187.5 250 250 8 100 mL/min 62.5* 125 187.5 250 312.5 7 2.5 Monitoring to Assess Safety, Efficacy, and Therapeutic Blood LevelsMonitor for signs and symptoms of digoxin toxicity and clinical response. Adjust dose based on toxicity, efficacy, and blood levels.
Serum digoxin levels less than 0.5 ng/mL have been associated with diminished efficacy, while levels above 2 ng/mL have been associated with increased toxicity without increased benefit.
Interpret the serum digoxin concentration in the overall clinical context, and do not use an isolated measurement of serum digoxin concentration as the basis for increasing or decreasing the DIGOXIN dose. Serum digoxin concentrations may be falsely elevated by endogenous digoxin-like substances [see Drug Interactions (7.4)]. If the assay is sensitive to these substances, consider obtaining a baseline digoxin level before starting DIGOXIN and correct post-treatment values by the reported baseline level.
Obtain serum digoxin concentrations just before the next scheduled DIGOXIN dose or at least 6 hours after the last dose. The digoxin concentration is likely to be 10-25% lower when sampled right before the next dose (24 hours after dosing) compared to sampling 8 hours after dosing (using once-daily dosing). However, there will be only minor differences in digoxin concentrations using twice daily dosing whether sampling is done at 8 or 12 hours after a dose.
2.6 Switching from Intravenous Digoxin to Oral DigoxinWhen switching from intravenous to oral digoxin formulations, make allowances for differences in bioavailability when calculating maintenance dosages (see Table 6).
Table 6. Comparison of the Systemic Availability and Equivalent Doses of Oral and Intravenous DIGOXINAbsolute
BioavailabilityEquivalent Doses (mcg)
DIGOXIN Tablets
60-80%
62.5
125
250
500
DIGOXIN Intravenous Injection
100%
50
100
200
400
-
Remedyrepack Inc.
Digoxin | Remedyrepack Inc.
Digoxin Tablets dose is based on patient-specific factors (age, lean body weight, renal function, etc.). See full prescribing information. Monitor for toxicity and therapeutic effect. (2)
In selecting a Digoxin Tablets dosing regimen, it is important to consider factors that affect digoxin blood levels (e.g., body weight, age, renal function, concomitant drugs) since toxic levels of digoxin are only slightly higher than therapeutic levels. Dosing can be either initiated with a loading dose followed by maintenance dosing if rapid titration is desired or initiated with maintenance dosing without a loading dose.
Consider interruption or reduction in Digoxin Tablets dose prior to electrical cardioversion [see Warnings and Precautions (5.4)].
Use digoxin solution to obtain the appropriate dose in infants, young pediatric patients, or patients with very low body weight.
For adults and pediatric patients if a loading dosage is to be given, administer half the total loading dose initially, then ¼ the loading dose every 6 to 8 hours twice, with careful assessment of clinical response and toxicity before each dose. The recommended loading dose is displayed in Table 1.
Table 1. Recommended Digoxin Tablets Oral Loading Dose Age Total Oral Loading Dose (mcg/kg)Administer half the total loading dose initially,
5 to 10 years 20 to 45 Adults and pediatric patients over 10 years 10 to 15 mcg = microgram
then ¼ the loading dose every 6 to 8 hours twiceThe maintenance dose is based on lean body weight, renal function, age, and concomitant products [see Clinical Pharmacology(12.3)].
The recommended starting maintenance dose in adults and pediatric patients over 10 years old with normal renal function is given in Table 2. Doses may be increased every 2 weeks according to clinical response, serum drug levels, and toxicity.
Table 2. Recommended Starting Digoxin Tablets Maintenance Dosage in Adults and Pediatric Patients Over 10 Years Old Age Total Oral Maintenance Dose, mcg/kg/day
(given once daily) Adults and pediatric patients over 10 years 3.4 to 5.1 mcg = microgramTable 3 provides the recommended (once daily) maintenance dose for adults and pediatric patients over 10 years old (to be given once daily) according to lean body weight and renal function. The doses are based on studies in adult patients with heart failure. Alternatively, the maintenance dose may be estimated by the following formula (peak body stores lost each day through elimination):
Total Maintenance Dose = Loading Dose (i.e., Peak Body Stores) x % Daily Loss/100
(% Daily Loss = 14 + Creatinine clearance/5)Reduce the dose of Digoxin Tablets in patients whose lean weight is an abnormally small fraction of their total body mass because of obesity or edema.
Table 3. Recommended Maintenance Dose (in micrograms given once daily) of Digoxin Tablets in Pediatric Patients Over 10 Years Old and Adults by Lean Body Weight and by Renal Functiona Corrected
Creatinine
Clearanceb Lean Body Weightd Number of Days
Before Steady
State Achievedc kg 40 50 60 70 80 90 100 10 mL/min 62.5* 125 125 187.5 187.5 187.5 250 19 20 mL/min 125 125 125 187.5 187.5 250 250 16 30 mL/min 125 125 187.5 187.5 250 250 312.5 14 40 mL/min 125 187.5 187.5 250 250 312.5 312.5 13 50 mL/min 125 187.5 187.5 250 250 312.5 312.5 12 60 mL/min 125 187.5 250 250 312.5 312.5 375 11 70 mL/min 187.5 187.5 250 250 312.5 375 375 10 80 mL/min 187.5 187.5 250 312.5 312.5 375 437.5 9 90 mL/min 187.5 250 250 312.5 375 437.5 437.5 8 100 mL/min 187.5 250 312.5 312.5 375 437.5 500 7 a Doses are rounded to the nearest dose possible using whole and/or half digoxin tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed.
b For adults, creatinine clearance was corrected to 70-kg body weight or 1.73 m2body surface area. If only serum creatinine concentrations (Scr) are available, a corrected Ccr may be estimated in men as (140 – Age)/Scr. For women, this result should be multiplied by 0.85.
For pediatric patients, the modified Schwartz equation may be used. The formula is based on height in cm and Scr in mg/dL where k is a constant. Ccr is corrected to 1.73 m2 body surface area. During the first year of life, the value of k is 0.33 for pre-term babies and 0.45 for term infants. The k is 0.55 for pediatric patients and adolescent girls and 0.7 for adolescent boys.
GFR (mL/min/1.73 m2) = (k x Height)/Scr
c If no loading dose administered.
d The doses listed assume average body composition.The starting maintenance dose for heart failure in pediatric patients less than 10 years old is based on lean body weight, renal function, age, and concomitant products [see Clinical Pharmacology (12.3)]. The recommended starting maintenance dose for pediatric patients between 5 years and 10 years old is given in Table 4. These recommendations assume the presence of normal renal function.
Table 4. Recommended Starting Digoxin Tablets Oral Maintenance Dosage in Pediatric Patients between 5 and 10 Years Old Age Oral Maintenance Dose,
mcg/kg/dose 5 years to 10 years 3.2 to 6.4 Twice dailyTable 5 provides average daily maintenance dose requirements for pediatric patients between 5 and 10 years old (to be given twice daily) with heart failure based on age, lean body weight, and renal function.
Table 5. Recommended Maintenance Dose (in micrograms given TWICE daily) of Digoxin Tablets in Pediatric Patients between 5 and 10 Years of Agea Based upon Lean Body Weight and Renal Functiona,b Corrected
Creatinine
Clearancec Lean Body Weight Number of Days
Before Steady
State Achievedd kg 20 30 40 50 60 10 mL/min - 62.5 62.5* 125 125 19 20 mL/min 62.5 2.5 125 125 125 16 30 mL/min 62.5 62.5* 125 125 187.5 14 40 mL/min 62.5 62.5* 125 187.5 187.5 13 50 mL/min 62.5 125 125 187.5 187.5 12 60 mL/min 62.5 125 125 187.5 250 11 70 mL/min 62.5 125 187.5 187.5 250 10 80 mL/min 62.5* 125 187.5 187.5 250 9 90 mL/min 62.5* 125 187.5 250 250 8 100 mL/min 62.5* 125 187.5 250 312.5 7a Recommended are doses to be given twice daily.
b The doses are rounded to the nearest dose possible using whole and/or half digoxin tablets. Recommended doses approximately 30 percent lower than the calculated dose are designated with an *. Monitor digoxin levels in patients receiving these initial doses and increase dose if needed.
c The modified Schwartz equation may be used to estimate creatinine clearance. See footnote b under Table 3.
d If no loading dose administered.Monitor for signs and symptoms of digoxin toxicity and clinical response. Adjust dose based on toxicity, efficacy, and blood levels.
Serum digoxin levels less than 0.5 ng/mL have been associated with diminished efficacy, while levels above 2 ng/mL have been associated with increased toxicity without increased benefit.
Interpret the serum digoxin concentration in the overall clinical context, and do not use an isolated measurement of serum digoxin concentration as the basis for increasing or decreasing the Digoxin Tablets dose. Serum digoxin concentrations may be falsely elevated by endogenous digoxin-like substances [see Drug Interactions (7.4)]. If the assay is sensitive to these substances, consider obtaining a baseline digoxin level before starting Digoxin Tablets and correct post-treatment values by the reported baseline level.
Obtain serum digoxin concentrations just before the next scheduled Digoxin Tablets dose or at least
6 hours after the last dose. The digoxin concentration is likely to be 10 to 25% lower when sampled right before the next dose (24 hours after dosing) compared to sampling 8 hours after dosing (using once-daily dosing). However, there will be only minor differences in digoxin concentrations using twice daily dosing whether sampling is done at 8 or 12 hours after a dose.
When switching from intravenous to oral digoxin formulations, make allowances for differences in bioavailability when calculating maintenance dosages (see Table 6).
Table 6. Comparison of the Systemic Availability and Equivalent Doses of Oral and Intravenous Digoxin Absolute
Bioavailability Equivalent Doses (mcg) Digoxin Tablets 60-80% 62.5 125 250 500 Digoxin Intravenous Injection 100% 50 100 200 400
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