Active Ingredient: Digoxin
Digoxin is indicated in the management of certain supraventricular arrhythmias, particularly chronic atrial fibrillation and flutter, where its major beneficial effect is to reduce the ventricular rate.
For this indication, competent medicine agencies globally authorize below treatments:
Oral
0.25 - 1.5 mg
From 0.25 To 1.5 mg once every day
The following schedules are intended as an initial guide but each patient has to be tailored individually according to age, lean body weight and renal function for his/her needs:
Suggested doses are intended only as an initial guide.
In cases where cardiac glycosides have been taken in the preceding two weeks the recommendations for initial dosing of a patient should be reconsidered and a reduced dose is advised.
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 I.V. formulation the dosage should be reduced by approximately 33%.
Rapid oral loading: 750-1500micrograms (0.75mg-1.5mg) as a single dose. If a greater risk or less urgency eg the elderly, the oral loading dose should be given in divided doses 6 hours apart, assessing clinical response, before giving each additional dose.
Slow oral loading: 250-750micrograms (0.25mg-0.75mg) should be given daily for 1 week, followed by appropriate maintenance dose. A clinical response should be seen within one week.
The clinical state of the patient and the urgency of the condition will depend on the choice between slow or rapid oral loading.
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:
Maintenance dose:
= peak body stores X % daily loss / 100
Where: peak body stores = loading dose; % daily loss = 14 + creatinine clearance (Ccr)/5.
Ccr is creatinine clearance corrected to 70kg body weight or 1.73m² body surface area. If only serum creatinine (Scr) concentrations are available, a Ccr (corrected to 70kg body weight) may be estimated in men as:
Ccr = 140-age / (Scr (in mg/100ml))
NB:
Serum creatinine values are in micromol/l, these can be converted to mg/100ml (mg/%) as follows:
Scr (mg/100ml) = Scr (micromol/L) x 113.12 / 10,000 = Scr (micromol/L) / 88.4
Where: 113.12 is the molecular weight of creatinine.
For Women: Multiply the result by 0.85.
This formulae cannot be used for creatinine clearance in children.
In practice, this will mean that most patients will be maintained on 0.125 to 0.25mg digoxin daily, however, in those who show increased sensitivity to the adverse effects of digoxin, a dosage of 62.5microgram (0.0625mg) daily or less may suffice. Conversely, some patients may require a higher dose.
Measurements of plasma levels of digoxin are useful in individualising therapy during the early stages of treatment, for detecting poor patient compliance and for diagnosing toxicity. 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 but most patients will benefit, with little risk of toxic symptoms and signs developing, with digoxin concentrations from 0.8 nanogram/ml, ng/ml (1.02 nanomol/litre, nm/L) to 2.0ng/ml (2.56nm/L). Above this range toxic symptoms and signs become more frequent and levels above 3ng/ml (3.84nm/L) are quite likely to be toxic. However, in deciding whether a patient’s symptoms are due to digoxin, the patent’s clinical state together with the serum potassium level and thyroid function are important factors. 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.
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 dosages of digoxin lower than those in non-elderly patients are used. Serum digoxin levels should be checked regularly and hypokalaemia avoided.
Intravenous
62 - 1,000 ug
From 62 To 1,000 ug once every day
Digoxin is for administration by slow intravenous infusion.
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.
If cases where cardiac glycosides have been taken in the preceding two weeks, the recommendations for initial dosing of a patient should be reconsidered and a reduced dose is advised.
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 I.V. formulation the dosage should be reduced by approximately 33%.
Emergency parenteral digitalisation (in patients who have not been given cardiac glycosides within the preceding two weeks):
Parenteral loading should only be used 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 micrograms (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 4-8 hours. An assessment of clinical response should be performed before giving each additional dose.
Each dose should be given by intravenous infusion over a period of 10-20 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:
Maintenance Dose = Peak body stores X % daily loss / 100
Where:
Peak body stores = Personalised Loading Dose
% Daily Loss = 14 + Creatinine Clearance (Ccr)/5
Ccr is creatinine clearance corrected to 70 kg body weight or 1.73 m² body surface area.
If only serum creatinine (Scr) concentrations are available, a Ccr (corrected to 70 kg body weight) may be estimated in men as
Ccr = (140-age) / Scr (in mg/100ml)
NOTE: Where serum creatinine values are obtained in micromol/L these may be converted to mg/100 ml (mg %) as follows:
Scr (mg/100ml) = Scr (micromol/L) X 113.12 / 10,000 = Scr (micromol/L) / 88.4
Where 113.12 is the molecular weight of creatinine.
For women, this result should be multiplied by 0.85.
NOTE: 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 micrograms (0.125 to 0.25 mg) digoxin daily; however in those who show increased sensitivity to the adverse effects of digoxin, a dosage of 62.5 microgram (0.0625 mg) daily or less may suffice. Conversely, some patients may require a higher dose.
Digoxin injection can be administered undiluted or diluted with a 4-fold or greater volume of 0.9% Sodium Chloride Injection, 0.18% Sodium Chloride/4% Glucose Injection or 5% Glucose Injection. A 4-fold volume of diluent equates to adding one 2 ml ampoule of digoxin to 6 ml of injection solution. The use of less than a 4-fold volume of diluent could lead to precipitation of digoxin.
Digoxin Injection may be diluted with the following solutions:
Sodium Chloride Intravenous Infusion BP 0.9% w/v
Glucose Intravenous Infusion BP 5.0% w/v
Sodium Chloride (0.18% w/v) and Glucose (4% w/v) Intravenous Infusion BP
When diluted in the ratio of 1 to 250 (i.e. one 2ml ampoule containing 500 micrograms digoxin added to 500ml of infusion solution), Digoxin Injection B.P. is known to be compatible with the above mentioned infusion solutions and stable for up to 48 hours at room temperature (20-25°C).
Dilution should be carried out either under full aseptic conditions or immediately prior to use. Any unused solution should be discarded.
Each dose should be given by intravenous infusion over of 10-20 minutes.
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 4-8 hours. An assessment of clinical response should be performed before giving each additional dose.
The intramuscular route is painful and is associated with muscle necrosis. This route cannot be recommended.
Rapid intravenous injection can cause vasoconstriction producing hypertension and/or reduced coronary flow. A slow injection rate is therefore important in hypertensive heart failure and acute myocardial infarction.
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