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Drug Details
LANOXIN
- Drug Class Description
Cardiac glycosides. - Generic Name
Digoxin - Presentation
Tablet. - Description
Digoxin Ph Eur 0.0625 mg/tablet - Indications
Lanoxin is indicated in the management of chronic cardiac failure where the dominant problem is systolic dysfunction. Its therapeutic benefit is greatest in those patients with ventricular dilatation. Lanoxin is specifically indicated where cardiac failure is accompanied by atrial fibrillation. Lanoxin is indicated in the management of certain supraventricular arrhythmias, particularly chronic atrial flutter and fibrillation. - Adult Dosage
The dose of Lanoxin 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 Lanoxin 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 %.
Adults with chronic cardiac failure in the absence of supraventricular arrhythmia:
No loading dose is required. The usual daily dose is 125 to 250 micrograms (0.125 to 0.25 mg) for patients with normal renal function. A lower dose of 62.5 micrograms (0.0625 mg) should be considered in the elderly.
For the management of atrial fibrillation or flutter in 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 micrograms (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, assessing clinical response before giving each additional dose (See Special Warnings and Precautions for Use).
Slow Oral Loading:
Digitalisation may be achieved more slowly with doses of 250 to 750 micrograms (0.25 to 0.75 mg) should be given 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.
Maintenance Dose:
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:
Where: Peak Body Stores = 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/100 ml) NOTE: Where serum creatinine values are obtained in micromol/L these may be converted to mg/100 ml (mg %) as follows:
Scr (mg/100 ml) = 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 will be maintained on 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.
Neonates, infants and children up to 10 years of age (if cardiac glycosides have not been given in the preceding two weeks):
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 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 microgram/kg over 24 hours Preterm neonates 1.5 kg to 2.5 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.
Maintenance Dose:
The maintenance dose should be administered in accordance with the following schedule:
Preterm neonates:
daily dose = 20% of 24-hour loading dose (intravenous or oral) Term neonates and children up to 10 years:
daily dose = 25% of 24-hour loading dose (intravenous or oral) These dosage schedules are meant as guidelines and careful clinical observation and monitoring of serum digoxin levels (see Monitoring) should be used as a basis for adjustment of dosage in these paediatric patient groups.
If cardiac glycosides have been given in the two weeks preceding commencement of Lanoxin therapy, it should be anticipated that optimum loading doses of Lanoxin will be less than those recommended above.
Use in the elderly:
The tendency to impaired renal function and low lean body mass in the elderly influences the pharmacokinetics of Lanoxin such that high serum digoxin levels and associated toxicity can occur quite readily, unless doses of Lanoxin lower than those in non-elderly patients are used. Serum digoxin levels should be checked regularly and hypokalaemia avoided.
Dose recommendations in renal disorder or with diuretic therapy:
See Special Warnings and Precautions for use.
Monitoring:
Serum concentrations of digoxin may be expressed in conventional units of nanogram/ml (ng/ml) or SI units of nanomol/L (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 Lanoxin. Several post hoc analyses of heart failure patients in the Digitalis Investigation Group trial suggest that the optimal trough digoxin serum level may be 0.5 ng/mL (0.64 nanomol/L) to 1.0 ng/mL (1.28 nanomol/L).
Digoxin toxicity is more commonly associated with serum digoxin concentration greater than 2 ng/mL. However, toxicity may occur with lower digoxin serum concentrations. In deciding whether a patient's symptoms are due to digoxin, the patient'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.
- Elderly Dosage
See data sheet. See data sheet. - Contra Indications
Lanoxin is contra-indicated in intermittent complete heart block or second degree atrioventricular block, especially if there is a history of Stokes-Adams attacks.
Lanoxin is contra-indicated in arrhythmias caused by cardiac glycoside intoxication.
Lanoxin is contra-indicated in 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 has been evaluated. If an accessory pathway is known or suspected to be present and there is no history of previous supraventricular arrhythmias, Lanoxin is similarly contra-indicated.
Lanoxin is contra-indicated in ventricular tachycardia or ventricular fibrillation.
Lanoxin is contra-indicated in hypertrophic obstructive cardiomyopathy, unless there is concomitant atrial fibrillation and heart failure but even then caution should be exercised if Lanoxin is to be used.
Lanoxin is contra-indicated in patients known to be hypersensitive to digoxin, other digitalis glycosides, or to any component of the preparation.
- Special Precautions
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 care, as clinically the rhythm resembles atrial fibrillation.
In some cases of sinoatrial disorder (i.e. Sick Sinus Syndrome) digoxin may cause or exacerbate sinus bradycardia or cause sinoatrial block.
Determination of the serum digoxin concentration may be very helpful in making a decision to treat with further digoxin, but toxic doses of other glycosides may cross-react in the assay and wrongly suggest apparently satisfactory measurements. Observations during the temporary withholding of digoxin might be more appropriate.
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 dosing recommendations should be reconsidered if patients are elderly or there are other reasons for the renal clearance of digoxin being reduced. A reduction in both initial and maintenance doses should be considered.
Hypokalaemia sensitises the myocardium to the actions of cardiac glycosides.
Hypoxia, hypomagnesaemia and marked hypercalcaemia increase myocardial sensitivity to cardiac glycosides.
Administering Lanoxin to a patient with thyroid disease requires care. Initial and maintenance doses of Lanoxin should be reduced when thyroid function is subnormal. In hyperthyroidism there is relative digoxin resistance and the dose may have to be increased. During the course of treatment of thyrotoxicosis, dosage should be reduced as the thyrotoxicosis comes under control.
Patients with malabsorption syndrome or gastro-intestinal reconstructions may require larger doses of digoxin.
The risk of provoking dangerous arrhythmias with direct current cardioversion is greatly increased in the presence of digitalis toxicity and is in proportion to the cardioversion energy used.
For elective direct current cardioversion of a patient who is taking digoxin, the drug should be withheld for 24 hours before cardioversion is performed. In emergencies, such as cardiac arrest, when attempting cardioversion the lowest effective energy should be applied. Direct current cardioversion is inappropriate in the treatment of arrhythmias thought to be caused by cardiac glycosides.
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.
The administration of digoxin in the period immediately following myocardial infarction is not contra-indicated. However, the use of inotropic drugs in some patients in this setting may result in undesirable increases in myocardial oxygen demand and ischaemia, and some retrospective follow-up studies have suggested digoxin to be associated with an increased risk of death. However, the possibility of arrhythmias arising in patients who may be hypokalaemic after myocardial infarction and are likely to be cardiologically unstable must be borne in mind. The limitations imposed thereafter on direct current cardioversion must also be remembered.
Treatment with digoxin should generally be avoided in patients with heart failure associated with cardiac amyloidosis. However, if alternative treatments are not appropriate, digoxin can be used with caution to control the ventricular rate in patients with cardiac amyloidosis and atrial fibrillation.
Digoxin can rarely precipitate vasoconstriction and therefore should be avoided in patients with myocarditis.
Patients with beri beri heart disease may fail to respond adequately to digoxin if the underlying thiamine deficiency is not treated concomitantly. There is also some published information indicating that digoxin may inhibit the uptake of thiamine in myocytes in beri beri heart disease.
Digoxin should not be used in constrictive pericarditis unless it is used to control the ventricular rate in atrial fibrillation or to improve systolic dysfunction.
Digoxin improves exercise tolerance in patients with impaired left ventricular systolic dysfunction and normal sinus rhythm. This may or may not be associated with an improved haemodynamic profile. However, the benefit of digoxin in patients with supraventricular arrythmias is most evident at rest, less evident with exercise.
In patients receiving diuretics and an ACE inhibitor, or diuretics alone, the withdrawal of digoxin has been shown to result in clinical deterioration.
The use of therapeutic doses of digoxin may cause prolongation of the PR interval and depression of the ST segment on the electrocardiogram.
Digoxin may produce false positive ST-T changes on the electrocardiogram during exercise testing. These electrophysiologic effects reflect an expected effect of the drug and are not indicative of toxicity.
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.
Although many patients with chronic congestive cardiac failure benefit from acute administration of digoxin, there are some in whom it does not lead to constant, marked or lasting haemodynamic improvement. It is therefore important to evaluate the response of each patient individually when Lanoxin is continued long-term.
Patients with severe respiratory disease may have an increased myocardial sensitivity to digitalis glycosides.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose galactose malabsorption should not take this medicine.
- Interactions
These may arise from effects on the renal excretion, tissue binding, plasma protein binding, distribution within the body, gut absorptive capacity and sensitivity to Lanoxin. Consideration of the possibility of an interaction whenever concomitant therapy is contemplated is the best precaution and a check on serum digoxin concentration is recommended when any doubt exists.
Digoxin, in association with beta-adrenoceptor blocking drugs, may increase atrio-ventricular conduction time.
Agents causing hypokalaemia or intracellular potassium deficiency may cause increased sensitivity to Digoxin; they include diuretics, lithium salts, corticosteroids and carbenoxolone.
Patients receiving Digoxin are more susceptible to the effects of suxamethonium-exacerbated hyperkalaemia.
Calcium, particularly if administered rapidly by the intravenous route, may produce serious arrhythmias in digitalized patients.
Serum levels of digoxin may be increased by concomitant administration of the following:
Alprazolam, amiodarone, diphenoxylate with atropine, flecainide, gentamicin, indomethacin, itraconazole, prazosin, propafenone, quinidine, quinine, spironolactone, macrolide antibiotics (e.g. neomycin), tetracycline (and possibly other antibiotics), trimethoprim and propantheline.
Serum levels of digoxin may be reduced by concomitant administration of the following:
Adrenaline, antacids, kaolin-pectin, some bulk laxatives and cholestyramine, acarbose, salbutamol, sulphasalazine, neomycin, rifampicin, some cytostatics, phenytoin, metoclopramide, penicillamine and the herbal remedy St John's wort (Hypericum perforatum).
Calcium channel blocking agents may either increase or cause no change in serum digoxin levels. Verapamil, felodipine and tiapamil increase serum digoxin levels. Nifedipine and diltiazem may increase or have no effect on serum digoxin levels. Isradipine causes no change in serum digoxin levels. Angiotensin converting enzyme (ACE) inhibitors may also increase or cause no change in serum digoxin concentrations.
Milrinone does not alter steady-state serum digoxin levels.
- Adverse Drug 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).Blood and lymphatic system disorders Very rare: Thrombocytopenia Metabolism and nutrition disorders Very Rare: Anorexia Psychiatric disorders Uncommon: Depression Very rare: Psychosis, apathy, confusion Nervous system disorders Common: CNS disturbances, dizziness Very rare: Headache Eye disorders Common: Visual disturbances (blurred or yellow vision) Cardiac disorders Common: Arrhythmia, conduction disturbances, bigeminy, trigeminy, PR prolongation, sinus bradycardia Very rare: Supraventricular tachyarrhythmia, atrial tachycardia (with or without block), junctional (nodal) tachycardia, ventricular arrhythmia, ventricular premature contraction, ST segment depression Gastrointestinal disorders Common: Nausea, vomiting, diarrhoea Very rare: Intestinal ischaemia, intestinal necrosis Skin disorders Common: Skin rashes of urticarial or scarlatiniform character may be accompanied by pronounced eosinophilia Reproductive system and breast disorders Very rare: Gynaecomastia can occur with long term administration General disorders and administration site conditions Very rare: Fatigue, malaise, weakness