Lanoxin 125 Tablets Ref.[2746] Active ingredients: Digoxin

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 (ie. 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 though to be caused by cardiac glycosides.

Many beneficial effects of digoxin on arrhythmias result from a degree of atrioventricular conduction blockage. 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 increased 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 patients with supraventricular arrhythmias 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 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, flecainide, gentamicin, indometacin, itraconazole, prazosin, propafenone, quinidine, quinine, spironolactone, macrolide antibiotics (e.g. erythromycin and clarithromycin), tetracycline (and possibly other antibiotics), trimethoprim, propantheline, atorvastatin, ciclosporin, epoprostenol (transient) and carvedilol.

Serum levels of digoxin may be reduced by concomitant administration of the following:

Adrenaline (epinephrine), antacids, kaolin-pectin, some bulk laxatives, colestyramine, acarbose, salbutamol, sulfasalazine, 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.

Digoxin is a substrate of P-glycoprotein. Thus, inhibitors of P-glycoprotein may increase blood concentrations of digoxin by enhancing its absorption and/or by reducing its renal clearance (See 5.2 Pharmacokinetic Properties).

No data are available on whether or not digoxin has teratogenic effects.

There is no information available on the effect of digoxin on human fertility.

The use of digoxin in pregnancy is not contra-indicated, although the dosage and control may be less predictable in pregnant than in non-pregnant women with some requiring an increased dosage of digoxin during pregnancy. As with all drugs, use should be considered only when the expected clinical benefit of treatment to the mother outweighs any possible risk to the developing foetus.

Despite extensive antenatal exposure to digitalis preparations, no significant adverse effects have been observed in the foetus or neonate when maternal serum digoxin concentrations are maintained within the normal range. Although it has been speculated that a direct effect of digoxin on the myometrium may result in relative prematurity and low birthweight, a contributing role of the underlying cardiac disease cannot be excluded. Maternally administered digoxin has been successfully used to treat foetal tachycardia and congestive heart failure.

Adverse foetal effects have been reported in mothers with digitalis toxicity.

Although digoxin is excreted in breast milk, the quantities are minute and breast feeding is not contra-indicated.

Since central nervous system and visual disturbances have been reported in patients receiving Lanoxin, patients should exercise caution before driving, using machinery or participating in dangerous activities.

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

None known.