DIXISOL Digoxin Injection B.P.

 500 mcg/ 2 ml


For the use of a Registered Medical Practitioner or a Hospital or a Institution only. 

The therapeutic benefit of digoxin is greater in patients with ventricular dilatation.
Cardiac failure is accompanied by atrial fibrillation.
Emergency parenteral digitilisation.
Certain supraventricular arrhythmias, particularly atrial fibrillation and flutter, where its major beneficial effect is to reduce the ventricular rate.

DIXISOL (Digoxin) is a cardiotonic glycoside obtained from the leaves of Digitalis lanata Ehrhart (Family- Scrophulariaceae). Chemically, digoxin is 3b-[(2,6-Dideoxy-b-D-ribo-hexopyranosyl-(1®4)-2,6-dideoxy-b-D-ribo-hexopyranosyl-(1®4)-2,6-dideoxy-b-D-ribo-hexopyranosyl)oxy]-12b,14-dihydroxy-5b-card-20(22)-enolide. The molecular formula is C41H64O14 and molecular weight is 781.

Its structural formula is :

  Digoxin Injection


DIXISOL is a sterile, nonpyrogenic, clear, colorless solution filled in amber ampoule of suitable size.

Each ml contains :

Digoxin B.P.                                   250 mcg
Ethanol (80 %) B.P.                        12.5 % v/v
Propylene Glycol B.P.                        40 % v/v
Water for Injections B.P.                             q.s.
Contains no preservatives.

Digoxin increases contractility of the myocardium by direct activity. This effect is proportional to dose in the lower range and some effect is achieved with quite low dosing; it occurs even in normal myocardium although it is then entirely without physiological benefit. The primary action of digoxin is specifically to inhibit adenosine triphosphatase and thus sodium-potassium (Na+-K+) exchange activity, the altered ionic distribution across the membrane resulting in an augmented calcium ion influx and thus an increase in the availability of calcium at the time of excitation-contraction coupling. The potency of digoxin may therefore appear considerably enhanced when the extracellular potassium concentration is low, with hyperkalaemia having the opposite effect. Digoxin exerts the same fundamental effect of inhibition of the Na+-K+ exchange mechanism on cells of the autonomic nervous system, stimulating them to exert indirect cardiac activity such as diminished impulse conduction rate through the atria and atrio-ventricular node (vagotonic) and senzitisation of the carotid sinus nerves (sympathomimetic). Indirect cardiac contractility changes also result from changes in venous compliance brought about by the altered autonomic activity and by direct venous stimulation. The interplay between direct and indirect activity governs the total circulatory response, which is not identical for all subjects. In the presence of certain supraventricular arrhythmias, the neurogenically mediated slowing of AV conduction is paramount.The degree of neurohormonal activation occurring in patients with heart failure is associated with clinical deterioration and an increased risk of death. Digoxin reduces activation of both the sympathetic nervous system and the (renin-angiotensin) system independently of its inotropic actions and may favourably influence survival. Whether this is achieved via direct sympathoinhibitory effects or by re-sensitizing baroreflex mechanisms remains unclear.

Intravenous administration of a loading dose produces an appreciable pharmacological effect within 5 to 30 minutes; this reaches a maximum in 1 to 5 hours.
The initial distribution of digoxin from the central to the peripheral compartment generally lasts from 6 to 8 hours. This is followed by a more gradual decline in serum digoxin concentration, which is dependent upon digoxin elimination from the body. The volume of distribution is large (Vdss = 510 litres in healthy volunteers), indicating digoxin to be extensively bound to body tissues. The highest digoxin concentrations are seen in the heart, liver and kidney that in the heart averaging 30- fold that in the systemic circulation. Although the concentration in skeletal muscle is far lower, this store cannot be overlooked since skeletal muscle represents 40 % of total body weight. Of the small proportion of digoxin circulating in plasma, approximately 25 % is bound to protein.
The major route of elimination is renal excretion of the unchanged drug.
Digoxin is a substrate for P-glycoprotein. As an efflux protein on the apical membrane of enterocytes, P-glycoprotein may limit the absorption of digoxin. P-glycoprotein in renal proximal tubules appears to be an important factor in the renal elimination of digoxin.
Following intravenous administration to healthy volunteers, between 60 and 75 % of a digoxin dose is recovered unchanged in the urine over a 6 day follow-up period. Total body clearance of digoxin has been shown to be directly related to renal function, and percent daily loss is thus a function of creatinine clearance, which in turn may be estimated from a stable serum creatinine. The total and renal clearances of digoxin have been found to be 193 ± 25 ml/min and 152 ± 24 ml/min in a healthy control population. 
In a small percentage of individuals, orally administered digoxin is converted to cardioinactivate reduction products (digoxin reduction products or DRPs) by colonic bacteria in the gastrointestinal tract. In these subjects over 40 % of the dose may be excreted as DRPs in the urine. Renal clearances of the two main metabolites, dihydrodigoxin and digoxygenin, have been found to be 79 ± 13 ml/min and 100 ± 26 ml/min respectively. In the majority of cases however, the major route of digoxin elimination is renal excretion of the unchanged drug. In the newborn period, renal clearance of digoxin is diminished and suitable dosage adjustments must be observed. This is specially pronounced in the premature infant since renal clearance reflects maturation of renal function. Digoxin clearance has been found to be 65.6 ± 30 ml/min/1.73 m2 at 3 months, compared to only 32 ± 7 ml/min/1.73 m2 at 1 week. Beyond the immediate newborn period, children generally require proportionally larger doses than adults on the basis of body weight and body surface area.
DIXISOL is indicated in the management of chronic cardiac failure. The therapeutic benefit of digoxin is greater in patients with ventricular dilatation. DIXISOL is specifically indicated where cardiac failure is accompanied by atrial fibrillation.
DIXISOL is indicated in the management of certain supraventricular arrhythmias, particularly atrial fibrillation and flutter, where its major beneficial effect is to reduce the ventricular rate. DIXISOL is indicated when emergency parenteral digitilisation is required in patients who have not been given cardiac glycosides within the preceding two weeks.

Administration :
Recommended dosages of DIXISOL may require considerable modification because of individual sensitivity of the patient to the drug, the presence of associated conditions, or the use of concurrent medications. Parenteral administration of digoxin should be used only when the need for rapid digitalization is urgent or when the drug cannot be taken orally. Intramuscular injection can lead to severe pain at the injection site, thus intravenous administration is preferred. If the drug must be administered by the intramuscular route, it should be injected deep into the muscle followed by massage. No more than 500 mcg (2 ml) should be injected into a single site. DIXISOL Injection can be administered undiluted or diluted with a 4-fold or greater volume of Sterile Water for Injection, 0.9 % Sodium Chloride Injection, or 5 % Dextrose Injection. The use of less than a 4-fold volume of diluent could lead to precipitation of the digoxin. Immediate use of the diluted product is recommended. If tuberculin syringes are used to measure very small doses, one must be aware of the problem of inadvertent over administration of digoxin. The syringe should not be flushed with the parenteral solution after its contents are expelled into an indwelling vascular catheter. Slow infusion of DIXISOL Injection is preferable to bolus administration. Rapid infusion of digitalis glycosides has been shown to cause systemic and coronary arteriolar constriction, which may be clinically undesirable. Caution is thus advised and DIXISOL Injection should probably be administered over a period of 5 minutes or longer. Mixing of DIXISOL Injection with other drugs in the same container or simultaneous administration in the same intravenous line is not recommended. 

The ampoule used in this product is equipped with O.P.C (One Point Cut) opening system. No ampoule file is needed to open the ampoule. The neck of the ampoule is prescored at the point of constriction. A coloured dot on the ampoule head helps to orientate the ampoule. Take the ampoule and face the coloured dot. Let the solution at the head of the ampoule to flow down by shaking or a gentle stroke. The ampoule opens easily by placing the thumb on the coloured dot and gently pressing downwards as shown.

        Ampoules equipped with One Point Cut (OPC) technology

Dosage :
In selecting a dose of digoxin, the following factors must be considered :
1. The body weight of the patient. Doses should be calculated based upon lean (i.e., ideal) body weight.
2. The patients renal function, preferably evaluated on the basis of estimated creatinine clearance.
3. The patients age. Infants and children require different doses of digoxin than adults. Also, advanced age may be indicative of diminished renal function even in patients with normal serum creatinine concentration (i.e., below 1.5 mg/dl).
4. Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharmacodynamic profile of digoxin.

Heart Failure
Adults :
Digitalization may be accomplished by either of two general approaches that vary in dosage and frequency of administration, but reach the same endpoint in terms of total amount of digoxin accumulated in the body.
1. If rapid digitalization is considered medically appropriate, it may be achieved by administering a loading dose based upon projected peak digoxin body stores. Maintenance dose can be calculated as a percentage of the loading dose.
2. More gradual digitalization may be obtained by beginning an appropriate maintenance dose, thus allowing digoxin body stores to accumulate slowly.Steady-state serum digoxin concentrations will be achieved in approximately five half-lives of the drug for the individual patient. Depending upon the patients renal function, this will take between 1 and 3 weeks. 

Rapid digitalization with a loading dose :
DIXISOL Injection is frequently used to achieve rapid digitalization, with conversion to digoxin tablets or digoxin capsules for maintenance therapy. If patients are switched from intravenous to oral digoxin formulations, allowances must be made for differences in bioavailability when calculating maintenance dosages Intramuscular injection of digoxin is extremely painful and offers no advantages unless other routes of administration are contraindicated. Peak digoxin body stores of 8 to 12 mcg/kg should provide therapeutic effect with minimum risk of toxicity in most patients with heart failure and normal sinus rhythm. Because of altered digoxin distribution and elimination, projected peak body stores for patients with renal insufficiency should be conservative (i.e., 6 to 10 mcg/kg). The loading dose should be administered in several portions, with roughly half the total given as the first dose. Additional fractions of this planned total dose may be given at 6- to 8-hour intervals, with careful assessment of clinical response before each additional dose. If the patients clinical response necessitates a change from the calculated loading dose of digoxin, then calculation of the maintenance dose should be based upon the amount actually given. A single initial intravenous dose of 400 to 600 mcg  (0.4 to 0.6 mg) of DIXISOL Injection usually produces a detectable effect in 5 to 30 minutes that becomes maximal in 1 to 4 hours. Additional doses of 100 to 300 mcg (0.1 to 0.3 mg) may be given cautiously at 6- to 8-hour intervals until clinical evidence of an adequate effect is noted. The usual 
amount of DIXISOL Injection that a 70-kg patient requires to achieve x8- to 12-mcg/kg peak body stores is  600  to 1,000 mcg (0.6 to 1.0 mg). 
Maintenance Dosing :
The maintenance dose 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 (i.e., Loading Dose) x % Daily Loss/100
Where : % Daily Loss = 14 + Ccr/5
(Ccr is creatinine clearance, corrected to 70 kg body weight or 1.73 m2 body surface area.)
Table 1 provides average daily maintenance dose requirements of DIXISOL Injection for patients with heart failure based upon lean body weight and renal function :
                 Digoxin Injection

a Daily maintenance doses have been rounded to the nearest 25-mcg increment.
b Ccr is creatinine clearance, corrected to 70-kg body weight or 1.73 m2 body surface area. For adults, if only serum creatinine concentrations (Scr) are available, a Ccr (corrected to 70 kg body weight) may be estimated in men as (140 - Age)/Scr. For women, this result should be multiplied by 0.85. Note : This equation cannot be used for estimating creatinine clearance in infants or children. 
c If no loading dose administered.
d 75 mcg = 0.075 mg.

Example : Based on the above table, a patient in heart failure with an estimated lean body weight of 70 kg and a Ccr of 60 ml/min should be given a dose of 175 mcg (0.175 mg) daily of DIXISOL Injection. If no loading dose is administered, steady-state serum concentrations in this patient should be anticipated at approximately 11days.

Atrial Fibrillation
Peak digoxin body stores larger than the 8 to 12 mcg/kg required for most patients with heart failure and normal sinus rhythm have been used for control of ventricular rate in patients with atrial fibrillation. Doses of digoxin used for the treatment of chronic atrial fibrillation 
should be titrated to the minimum dose that achieves the desired ventricular rate control without causing undesirable side effects. Data are not available to establish the appropriate resting or exercise target rates that should be achieved.
DIXISOL is contra-indicated in intermittent complete heart block or second degree atrioventricular block, especially if there is a history of Stokes-Adams attacks. DIXISOL is contra-indicated in arrhythmias caused by cardiac glycoside intoxication. DIXISOL 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 have been evaluated. If an accessory pathway is known or suspected to be present and there is no history of previous supraventricular arrhythmias, DIXISOL is similarly contra-indicated. DIXISOL is contra-indicated in ventricular tachycardia or ventricular fibrillation. DIXISOL is contra-indicated in hypertrophic obstructive cardiomyopathy, unless there is concomitant atrial fibrillation and heart failure but even then caution should be exercised if DIXISOL is to be used. DIXISOL is contra-indicated in patients known to be hypersensitive to digoxin or other digitalis glycosides or to any component of the preparation. 

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. In some cases of sinoatrial disorder (i.e. Sick Sinus Syndrome) digoxin may cause or exacerbate sinus bradycardia or cause sinoatrial block. 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 ischemia, and some retrospective follow-up studies have suggested digoxin to be associated with an increased risk of death. The possibility of arrhythmias arising in patients who may be hypokalaemic after myocardial infarction and are likely to be haemodynamically 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 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. DIXISOL should not be used in constrictive pericarditis unless it is used to control the ventricular rate in arterial 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. 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 electro physiologic effects reflect an expected effect of the drug and are not indicative of toxicity. 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.

Patients receiving DIXISOL should have their serum electrolytes and renal function (serum creatinine concentration) assessed periodically; the frequency of assessments will depend on the clinical setting. 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 may cross-react in the assay giving false-positive results. Observations while temporarily withholding digoxin might be more appropriate. Patients with severe respiratory disease may have an increased myocardial sensitivity to digitalis glycosides. Hypokalaemia sensitises the myocardium to the actions of cardiac glycosides. 

Direct current cardioversion :
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. Rapid intravenous injection can cause vaso-constriction producing hypertension and/or reduced coronary flow. A slow injection rate is therefore important in hypertensive heart failure and acute myocardial infarction.

Laboratory Tests : 
Patients receiving digoxin should have their serum electrolytes and renal function (BUN and/or serum creatinine) assessed periodically; the frequency of assessments will depend on the clinical setting.


Pregnancy : Category C
Teratogenic Effects :
Animal reproduction studies have not been conducted with digoxin. It is also not known whether digoxin can cause foetal harm when administered to a pregnant woman or can affect reproductive capacity. Digoxin should be given to a pregnant woman only if clearly needed.

Nursing mothers :
Studies have shown that digoxin concentrations in the mothers serum and milk are similar. However, the estimated exposure of a nursing infant to digoxin via breastfeeding will be far below the usual infant maintenance dose. Therefore, this amount should have no pharmacologic effect upon the infant. Nevertheless, caution should be exercised when digoxin is administered to a nursing woman. 

Paediatric Use :
Newborn infants display considerable variability in their tolerance to digoxin. Premature and immature infants are particularly sensitive to the effects of digoxin, and the dosage of the drug must not only be reduced but must be individualized according to their degree of maturity. Digitalis glycosides can cause poisoning in children due to accidental ingestion.
Potassium-depleting diuretics are a major contributing factor to digitalis toxicity. Calcium, particularly if administered rapidly by the intravenous route, may produce serious arrhythmias in digitalized patients. Quinidine, verapamil, amiodarone, propafenone, indomethacin, itraconazole, alprazolam, and spironolactone raise the serum digoxin concentration due to a reduction in clearance and/or volume of distribution of the drug, with the implication that digitalis intoxication may result. Erythromycin and clarithromycin (and possibly other macrolide antibiotics) and tetracycline may increase digoxin absorption in patients who inactivate digoxin by bacterial metabolism in the lower intestine, so that digitalis intoxication may result. Propantheline and diphenoxylate, by decreasing gut motility, may increase digoxin absorption. Antacids, kaolin-pectin, sulfasalazine, neomycin, cholestyramine, certain anticancer drugs, and metoclopramide may interfere with intestinal digoxin absorption, resulting in unexpectedly low serum concentrations. Rifampin may decrease serum digoxin concentration, especially in patients with renal dysfunction, by increasing the non-renal clearance of digoxin. There have been inconsistent reports regarding the effects of other drugs (e.g., quinine, Penicillamine) on serum digoxin concentration. Thyroid administration to a digitalized, hypothyroid patient may increase the dose requirement of digoxin. Concomitant use of digoxin and sympathomimetics increases the risk of cardiac arrhythmias. Succinylcholine may cause a sudden extrusion of potassium from muscle cells, and may thereby cause arrhythmias in digitalized patients. Although calcium channel blockers and digoxin may be useful in combination to control atrial fibrillation, their additive effects on AV node conduction can result in advanced or complete heart block. Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia. Digoxin concentrations are increased by about 15 % when digoxin and carvedilol are administered concomitantly. Therefore, increased monitoring of digoxin is recommended when initiating, adjusting, or discontinuing carvedilol. Due to the considerable variability of these interactions, dosage of digoxin should be individualized when patients receive these medications concurrently. Furthermore, caution should be exercised when combining digoxin with any drug that may cause a significant deterioration in renal function, since a decline in glomerular filtration or tubular secretion may impair the excretion of digoxin.
Since central nervous system and visual disturbances have been reported in patients receiving DIXISOL, patients should exercise caution before driving, using machinery or participating in dangerous activities. 
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. 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 : Thrombocytopaenia
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.

Symptoms and signs :
The systems and signs of toxicity are generally similar to those described in the Side effects section but may be more frequent and can be more severe. Signs and symptoms of digoxin toxicity become more frequent with levels above 3.0 nanograms/ml (3.84 nanomol/l) although there is considerable interindividual variation. However, in deciding whether a patients symptoms are due to digoxin, the clinical state, together with serum electrolyte levels and thyroid function are important factors. 

Adults :
In adults without heart disease clinical observation suggests that an overdose of digoxin of 10 -15 mg was the dose resulting in death of half of the patients. If more than 25 mg of digoxin was ingested by an adult without heart disease, death or progressive toxicity responsive only to digoxin-binding Fab antibody fragments resulted.

Cardiac manifestations :
Cardiac manifestations are the most frequent and serious sign of both acute and chronic toxicity. Peak cardiac effects generally occur 3 to 6 hours following overdosage and may persist for the ensuing 24 hours or longer. Digoxin toxicity may result in almost any type of arrhythmia. Multiple rhythm disturbances in the same patient are common. These include paroxysmal atrial tachycardia with variable atrioventricular (AV) block, accelerated junctional rhythm, slow atrial fibrillation (with very little variation in the ventricular rate) and bi directional ventricular tachycardia. Premature ventricular contractions (PVCs) are often the earliest and most common arrhythmia. Bigeminy or trigeminy also occur frequently. Sinus bradycardia and other bradyarrhythmias are very common. First, second, third degree heart blocks and AV dissociation are also common. Early toxicity may only be manifested by prolongation of the PR interval. Ventricular tachycardia may also be a manifestation of toxicity. Cardiac arrest from asystole or ventricular fibrillation due to digoxin toxicity is usually fatal. Acute massive digoxin overdosage can result in mild to pronounced hyperkalaemia due to inhibition of the sodium-potassium (Na+-K+) pump. Hypokalaemia may contribute to toxicity. 

Non-cardiac manifestations :
Gastrointestinal symptoms are very common in both acute and chronic toxicity. The symptoms precede cardiac manifestations in approximately half of the patients in most literature reports. Anorexia, nausea and vomiting have been reported with an incidence up to 80 %. These symptoms usually present early in the course of an overdose. Neurologic and visual manifestations occur in both acute and chronic toxicity. Dizziness, various CNS disturbances, fatigue and malaise are very common. The most frequent visual disturbance is an aberration of colour vision (predominance of yellow green). These neurological and visual symptoms may persist even after other signs of toxicity have resolved. In chronic toxicity, non-specific extracardiac symptoms, such as malaise and weakness, may predominate.

Children :
In children aged 1 to 3 years without heart disease, clinical observation suggests that an overdose of digoxin of 6 to 10 mg was the dose resulting in death in half of the patients. If more than 10 mg of digoxin was ingested by a child aged 1 to 3 years without heart disease, the outcome was uniformly fatal when Fab fragment treatment was not given. Most manifestations of toxicity in children occur during or shortly after the loading phase with digoxin.
Cardiac manifestations :
The same arrhythmias or combination of arrhythmias that occur in adults can occur in paediatrics. Sinus tachycardia, supraventricular tachycardia, and rapid atrial fibrillation are seen less frequently in the paediatric population. Paediatric patients are more likely to present with an AV conduction disturbance or a sinus bradycardia. Ventricular ectopy is less common, however in massive overdose, ventricular ectopy; ventricular tachycardia and ventricular fibrillation have been reported. In neonates, sinus bradycardia or sinus arrest and/or prolonged PR intervals are frequent signs of toxicity. Sinus bradycardia is common in young infants and children. In older children, AV blocks are the most common conduction disorders. Any arrhythmia or alteration in cardiac conduction that develops in a child taking digoxin should be assumed to be caused by digoxin, until further evaluation proves otherwise. 

In addition to cardiac monitoring, digoxin should be temporarily discontinued until the adverse reaction resolves and may be all that is required to treat the adverse reaction such as in asymptomatic bradycardia or digoxin related heart block. Every effort should also be made to correct factors that may contribute to the adverse reaction (such as electrolyte disturbances, thyroid function, or concurrent medications) Once the adverse reaction has resolved, therapy with digoxin may be reinstituted, following a careful reassessment of dose. When the primary manifestation of digoxin overdosage is a cardiac arrhythmia, additional therapy may be needed. If the rhythm disturbance is a symptomatic bradyarrhythmia or heart block, consideration should be given to the reversal of toxicity with Digoxin Immune Fab (Ovine), the use of atropine, or the insertion of a temporary cardiac pacemaker. Digoxin Immune Fab (Ovine) is a specific antidote for digoxin and may be used to reverse potentially life-threatening ventricular arrhythmias due to digoxin overdosage.
Massive Digitalis Overdosage : 
Manifestations of life-threatening toxicity include ventricular tachycardia or ventricular fibrillation, or progressive bradyarrhythmias, or heart block. Digoxin Immune Fab (Ovine) should be used to reverse the toxic effects of ingestion of a massive overdose. The decision to administer Digoxin Immune Fab (Ovine) to a patient who has ingested a massive dose of digoxin but who has not yet manifested life-threatening toxicity should depend on the likelihood that life-threatening toxicity will occur. Digoxin is not effectively removed from the body by dialysis due to its large extravascular volume of distribution. Patients with massive digitalis ingestion should receive large doses of activated charcoal to prevent absorption and bind digoxin in the gut during enteroenteric recirculation. Emesis may be indicated especially if ingestion has occurred within 30 minutes of the patients presentation at the hospital. Emesis should not be induced in patients who are obtunded. If a patient presents more than 2 hours after ingestion or already has toxic manifestations, it may be unsafe to induce vomiting because such maneuvers may induce an acute vagal episode that can worsen digitalis-related arrhythmias. In cases where a large amount of digoxin has been ingested, hyperkalemia may be present due to release of potassium from skeletal muscle. Hyperkalaemia caused by massive digitalis toxicity is best treated with Digoxin Immune Fab (Ovine); initial treatment with glucose and insulin may also be required if hyperkalaemia itself is acutely life-threatening. 

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. 

Store below  30°C (86°F), protected from light. Do not refrigerate. Avoid exposure to excessive heat.
24 months from the date of manufacture.

DIXISOL is supplied as 500 mcg of Digoxin B.P. in 2 ml aqueous solution. Such 5 Ampoules of  2 ml are packed in a Box.
Disclaimer : For the use of a Registered Medical Practitioner or a Hospital or a Institution only. Also it is not intended to be used by healthcare professionals or patients for the purpose of prescribing or administering these products. Questions regarding the complete and current content of product labeling / specification / presentation should be directed to SGPharma.
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