The dose of digoxin for each patient has to be tailored individually according to age, lean body weight and renal function.
Suggested doses are intended only as an initial guide.
The difference in bioavailability between injectable digoxin and oral formulations must be considered when changing from one dosage form to another. For example if patients are switched from oral to the intravenous formulation the dosage should be reduced by approximately 33%.
Lanoxin PG Elixir, 50 mcg in 1 ml, is supplied with a graduated pipette and this should be used for measurement of all doses.
Serum concentrations of digoxin may be expressed in Conventional Units of ng/ml or SI Units of nmol/l. To convert ng/ml to nmol/l, multiply ng/ml by 1.28. The serum concentration of digoxin can be determined by radioimmunoassay.
Blood should be taken 6 hours or more after the last dose of digoxin.
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 Digitalis Investigation Group trial demonstrated that at low serum digoxin concentrations (0.5 - 0.9 ng/ml), the use of digoxin was associated with reductions in mortality and hospitalization. Patients with higher digoxin levels (>1 ng/ml) had a higher incidence of morbidity and mortality, although at these concentrations digoxin reduces heart failure hospitalization. Therefore, the optimal trough digoxin serum level may be 0.5 ng/ml (0.64 nmol/l) to 1.0 ng/ml (1.28 nmol/l).
Digoxin toxicity is more commonly associated with serum digoxin concentration greater than 2 ng/ml. However, serum digoxin concentration should be interpreted in the clinical context. Toxicity may occur with lower digoxin serum concentrations. In deciding whether a patient's symptoms are due to digoxin, the clinical state together with the serum potassium level and thyroid function are important factors (see Overdosage).
Other glycosides, including metabolites of digoxin, can interfere with the assays that are available and one should always be wary of values which do not seem commensurate with the clinical state of the patient.
Tablet/PG Elixir: Adults and children over 10 years: Rapid Oral Loading:
If medically appropriate, rapid digitalisation may be achieved in a number of ways, such as the following: 750 to 1500 μg (0.75 to 1.5 mg) as a single dose.
Where there is less urgency, or greater risk of toxicity e.g. in the elderly, the oral loading dose should be given in divided doses 6 hours apart, with approximately half the total dose given as the first dose.
Clinical response should be assessed before giving each additional dose (see Precautions).
Slow Oral Loading:
In some patients, for example those with mild heart failure, digitalization may be achieved more slowly with doses of 250 to 750 μg (0.25 to 0.75 mg) daily for 1 week followed by an appropriate maintenance dose. A clinical response should be seen within one week.
NOTE: The choice between slow and rapid oral loading depends on the clinical state of the patient and the urgency of the condition.
Injection: Adults and children over 10 years: Parenteral Loading:
(for use in patients who have not been given cardiac glycosides within the preceding two weeks).
The total loading dose of parenteral digoxin is 500 to 1000 μg (0.5 to 1.0 mg) depending on age, lean body weight and renal function. The total loading dose should be administered in divided doses with approximately half of the total dose given as the first dose and further fractions of the total dose given at intervals of 4 to 8 hours. An assessment of clinical response should be performed before giving each additional dose.
Each dose should be given by intravenous infusion (see Special precautions for disposal and other handling under Cautions for Usage) over 10 to 20 minutes.
The maintenance dosage should be based upon the percentage of the peak body stores lost each day through elimination. The following formula has had wide clinical use: See Equation 1.
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is creatinine clearance corrected to 70 kg bodyweight or 1.73 m2
body surface area.
If only serum creatinine (Scr
) concentrations are available, a Ccr
(corrected to 70 kg bodyweight) may be estimated in men as: See Equation 2.
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NOTE: Where serum creatinine values are obtained in μmol/l, these may be converted to mg/100 ml (mg %) as follows: See Equation 3.
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, this result should be multiplied by 0.85.
These formulae cannot be used for creatinine clearance in children.
In practice, this will mean that most patients with heart failure will be maintained on 125 to 250 μg (0.125 to 0.25 mg) digoxin daily; however in those who show increased sensitivity to the adverse effects of digoxin, a dose of 62.5 μg (0.0625 mg) daily or less may suffice. Conversely, some patients may require a higher dose.
Neonates, infants and children up to 10 years of age
(if cardiac glycosides have not been given in the preceding two weeks): If cardiac glycosides have been given in the two weeks preceding commencement of digoxin therapy, it should be anticipated that optimum loading doses of digoxin will be less than those recommended as follows.
In the newborn, particularly in the premature infant, renal clearance of digoxin is diminished and suitable dose reductions must be observed, over and above general dosage instructions.
Beyond the immediate newborn period, children generally require proportionally larger doses than adults on the basis of body weight or body surface area, as indicated in the schedule as follows. Children over 10 years of age require adult dosages in proportion to their body weight.
Oral loading dose:
This should be administered in accordance with the following schedule: Preterm neonates < 1.5 kg: 25 μg/kg per 24 hours.
Preterm neonates 1.5 kg to 2.5 kg: 30 μg/kg per 24 hours.
Term neonates to 2 years: 45 μg/kg per 24 hours.
2 to 5 years: 35 μg/kg per 24 hours.
5 to 10 years: 25 μg/kg per 24 hours.
The loading dose should be administered in divided doses with approximately half the total dose given as the first dose and further fractions of the total dose given at intervals of 4 to 8 hours, assessing clinical response before giving each additional dose.
Injection: Parenteral loading dose:
The intravenous loading dose in the previously mentioned groups should be administered in accordance with the following schedule: Preterm neonates <1.5 kg: 20 μg/kg over 24 hours.
Preterm neonates 1.5 kg - 2.5 kg: 30 μg/kg over 24 hours.
Term neonates to 2 years: 35 μg/kg over 24 hours.
2 to 5 years: 35 μg/kg over 24 hours.
5 to 10 years: 25 μg/kg over 24 hours.
The loading dose should be administered in divided doses with approximately half the total dose given as the first dose and further fractions of the total dose given at intervals of 4 to 8 hours, assessing clinical response before giving each additional dose. Each dose should be given by intravenous infusion (see Special precautions for disposal and other handling under Cautions for Usage) over 10 to 20 minutes.
The maintenance dose should be administered in accordance with the following schedule: Preterm neonates: daily dose = 20% of 24-hour loading dose (intravenous).
Term neonates and children up to 10 years: daily dose = 25% of 24-hour loading dose (intravenous).
These dosage schedules are meant as guidelines and careful clinical observation and monitoring of serum digoxin levels (see Precautions) should be used as a basis for adjustment of dosage in these paediatric patient groups.
The tendency to impaired renal function and low lean body mass in the elderly influences the pharmacokinetics of digoxin such that high serum digoxin levels and associated toxicity can occur quite readily, unless doses of digoxin lower than those in non-elderly patients are used. Serum digoxin levels should be checked regularly and hypokalaemia avoided.
Dose Recommendations in Specific Patients Groups:
Injection: Dilution of digoxin injection:
Digoxin Injection can be administered undiluted or diluted with a 4-fold or greater volume of diluent. The use of less than a 4-fold volume of diluent could lead to precipitation of digoxin. Digoxin injection, 250 μg per ml when diluted in the ratio of 1 to 250 (i.e. One 2 ml ampoule containing 500 μg added to 500 ml of infusion solution) is known to be compatible with the following infusion solutions and stable for up to 48 hours at room temperature (20 to 25°C): Sodium Chloride Intravenous Infusion, B.P., 0.9% w/v.
Sodium Chloride (0.18% w/v) and Glucose (4% w/v) Intravenous Infusion, B.P.
Glucose Intravenous Infusion, B.P., 5% w/v.
Dilution should be carried out either under full aseptic conditions or immediately before use. Any unused solution should be discarded.