DIGOXIN

Posology:

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. 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. V. formulation the dosage should be reduced by approximately 33 %. 5 mg) as a single dose.

g. in the elderly, the oral loading dose should be given in divided doses six hours apart, with approximately half the total dose given as the first dose. 4). 75 mg) daily for one week followed by an appropriate maintenance dose. A clinical response should be seen within one week.

Maintenance dose:

The maintenance dosage should be based upon the percentage of the peak body stores lost each day through elimination. The choice between slow and rapid oral loading depends on the clinical state of the patient and the urgency of the condition.

73 m2 body surface area. 12 is the molecular weight of creatinine. 85.

NOTE:

These formulae cannot be used for creatinine clearance in children. 125 to 0. 0625 mg) daily or less may suffice. Conversely, some patients may require a higher dose. Neonates, infants and paediatric populations up to 10 years of age 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 below.

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 below.

Children over ten years of age require adult dosages in proportion to their body weight. 5 kg 30 microgram/kg over 24 hours Term neonates to 2 years 45 microgram/kg over 24 hours 2 to 5 years 35 microgram/kg over 24 hours 5 to 10 years 25 microgram/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.

Summary of the safety profile In general, the adverse reactions of digoxin are dose-dependent and occur at doses higher than those needed to achieve a therapeutic effect. Hence, adverse reactions are less common when digoxin is used within the recommended dose range or therapeutic serum concentration range and when there is careful attention to concurrent medications and conditions.

Tabulated list of adverse reactions Adverse reactions are listed below by system organ class and frequency.

Frequencies are defined as:

Very common ≥ 1/10 Common ≥ 1/100 and < 1/10 Uncommon ≥ 1/1000 and < 1/100 Rare ≥ 1/10,000 and < 1/1000 Very rare < 1/10,000, including isolated reports. Very common, common and uncommon events were generally determined from clinical trial data.

The incidence in placebo was taken into account. Adverse drug reactions identified through post- marketing surveillance were considered to be rare or very rare (including isolated reports). System Organ Class Frequency Side effects Blood and lymphatic system disorders Very rare Thrombocytopaenia Metabolism and nutrition disorders Very rare Decreased appetite Psychiatric disorders Uncommon Depression Very rare Psychotic disorder, apathy, confusional state Common Nervous system disorder, dizzinessNervous system disorders Very rare Headache Eye disorders Common Visual impairment (blurred vision or xanthopsia) Cardiac disorders Common Arrhythmia, conduction disturbances, bigeminy, trigeminy, PR prolongation, sinus bradycardia Very rare Supraventricular tachyarrhythmia, atrial tachycardia (with or without block), supraventricular tachycardia (nodal arrhythmia), ventricular arrhythmia, ventricular extrasystoles, premature contraction, electrocardiogram ST segment depression Common Nausea, vomiting, diarrhoeaGastrointestinal disorders Very rare Intestinal ischaemia, gastrointestinal necrosis Skin and subcutaneous tissue Disorders Common Rash* Reproductive system and breast disorders Very rare Gynaecomastia* General disorders and administration site conditions Very rare Fatigue, malaise, asthenia (weakness) * See “Description of selected adverse reactions” Description of selected adverse reactions Skin and subcutaneous tissue disorders Skin rashes of urticarial or scarlatiniform character may be accompanied by pronounced eosinophilia.

Monitoring Patients receiving digoxin should have their serum electrolytes and renal function (serum creatinine concentration) assessed periodically; the frequency of assessments will depend on the clinical setting. Serum concentrations of digoxin may be expressed in Conventional Units of nanograms/ml or SI Units of nanomol/l.

28. The serum concentration of digoxin can be determined by radioimmunoassay. Blood should be taken six 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.

28 nanomol/l). Digoxin toxicity is more commonly associated with serum digoxin concentrations greater than 2 nanogram/ml. However, serum digoxin concentration should be interpreted in the clinical context. Toxicity may occur with lower digoxin serum concentrations.

9). Determination of the serum digoxin concentration may be very helpful in making a decision to treat with further digoxin, but other glycosides and endogenous digoxin-like substances, 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.

Observations while temporary withholding digoxin might be more appropriate. Arrhythmias Arrhythmias may be precipitated by digoxin toxicity, some of which can resemble arrhythmias for which the drug could be advised. For example, atrial tachycardia with varying atrioventricular block requires particular care as clinically the rhythm resembles atrial fibrillation.

Many beneficial effects of digoxin on arrhythmias result from a degree of atrioventricular conduction blockade. However, when incomplete atrioventricular block already exists the effects of a rapid progression in the block should be anticipated.

In complete heart block the idioventricular escape rhythm may be suppressed. e. Sick Sinus Syndrome) digoxin may cause or exacerbate sinus bradycardia or cause sinoatrial block. Myocardial infarction The administration of digoxin in the period immediately following myocardial infarction is not contraindicated.

1 - intermittent complete heart block or second degree atrioventricular block, especially if there is a history of Stokes-Adams attacks. - arrhythmias caused by cardiac glycoside intoxication. - supraventricular arrhythmias associated with an accessory atrioventricular pathway, as in the Wolff-Parkinson-White Syndrome, unless the electrophysiological characteristics of the accessory pathway and any possible deleterious effect of digoxin on these characteristics have been evaluated.

If an accessory pathway is known or suspected to be present and there is no history of previous supraventricular arrhythmias, Digoxin is similarly contra-indicated. - ventricular tachycardia or ventricular fibrillation. - hypertrophic obstructive cardiomyopathy, unless there is concomitant atrial fibrillation and heart failure but even then caution should be exercised if digoxin is to be used.