2.1 Important Dosing and Administration Information
In selecting a DIGITEK® (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 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 Patients
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 DIGITEK® (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 years to 10 years
20 to 45
Adults and pediatric patients over 10 years
10 to 15
mcg = micrograms
2.3 Maintenance Dosing in Adults and Pediatric Patients over 10 Years Old
The 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 DIGITEK® (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 = micrograms
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 DIGITEK® (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 DIGITEK® (digoxin tablets) in Pediatric Patients Over 10 Years Old and Adults by Lean Body Weight and by Renal Function*
*
Doses are rounded to the nearest dose possible using whole and/or half DIGITEK
® (digoxin tablets) tablets. Recommended doses approximately 30% 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 x Height)/Scr
‡
The doses listed assume average body composition.
§
If no loading dose administered.
Corrected Creatinine Clearance†
Lean Body Weight‡
Number
of Days
Before
Steady
State
Achieved§
kg
40
50
60
70
80
90
100
lb
88
110
132
154
176
198
220
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 Old
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 and 10 years old is given in Table 4. These recommendations assume the presence of normal renal function.
Table 4. Recommended Starting DIGITEK® (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 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 DIGITEK® (digoxin tablets) in Pediatric Patients between 5 and 10 Years of Age* Based upon Lean Body Weight and Renal Function*, †
*
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.
Corrected
Creatinine
Clearance‡
Lean Body Weight
Number of
Days
Before
Steady
State
Achieved§
kg
20
30
40
50
60
lb
44
66
88
110
132
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 Levels
Monitor for signs and symptoms of digoxin toxicity and clinical response. Adjust dose based on toxicity, efficacy and blood levels.
Serum digoxin levels < 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 DIGITEK® (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 DIGITEK® (digoxin tablets) and correct post-treatment values by the reported baseline level.
Obtain serum digoxin concentrations just before the next scheduled DIGITEK® (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 Digoxin
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 DIGITEK® (digoxin tablets)
Absolute Bioavailability
Equivalent Doses (mcg)
DIGITEK® (digoxin tablets)
60% to 80%
62.5
125
250
500
Digoxin Intravenous Injection
100%
50
100
200
400
