Updated on 01 October 2024
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Updated on 01 October 2024
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Updated on 14 September 2022
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Updated on 26 August 2022
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Updated on 26 August 2022
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Updated on 09 July 2020
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Digo_Tab_IE_S_0.0625mg_v5.pdf
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- Change to section 4.2 - Posology and method of administration
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Updated on 09 July 2020
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Updated on 11 March 2019
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Updated on 22 January 2019
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Updated on 22 January 2019
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Updated on 23 October 2018
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Updated on 17 October 2018
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Updated on 10 May 2018
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Updated on 21 April 2017
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PIL_9868_983.pdf
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Updated on 21 April 2017
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- Change to section 2 - pregnancy, breast feeding and fertility
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- Change to section 3 - how to take/use
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- Change to section 4 - how to report a side effect
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Updated on 19 April 2017
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- New SPC for new product
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Updated on 19 April 2017
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- Change to section 4.1 - Therapeutic indications
- Change to section 4.2 - Posology and method of administration
- Change to section 4.3 - Contraindications
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 4.6 - Pregnancy and lactation
- Change to section 4.8 - Undesirable effects
- Change to Section 4.8 – Undesirable effects - how to report a side effect
- Change to section 4.9 - Overdose
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 5.2 - Pharmacokinetic properties
- Change to section 5.3 - Preclinical safety data
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10 DATE OF REVISION OF THE TEXT
April 2017 2014
5.3 Preclinical safety data
Carcinogenesis, mutagenesis
Digoxin showed no genotoxic potential in in vitro studies (Ames test and mouse lymphoma). No data are available on the carcinogenic potential of digoxin.
5.2 Pharmacokinetic properties
Absorption
The Tmax following IV administration is approximately 1 to 5 hours, while the Tmax for oral administration is 2 to 6 hours. Upon oral administration, digoxin is absorbed from the stomach and upper part of the small intestine. When digoxin is taken after meals, the rate of absorption is slowed, but the total amount of digoxin absorbed is usually unchanged. When taken with meals high in fibre, however, the amount absorbed from an oral dose may be reduced.
Biotransformation
The majority of digoxin is excreted by the kidneys as an intact drug, although a small fraction of the dose is metabolised to pharmacologically active and inactive metabolites. The main metabolites of digoxin are dihydrodigoxin and digoxygenin.
The terminal elimination half-life of digoxin in patients with normal renal function is 30 to 40 h.
Paediatric population
In the newborn period, renal clearance of digoxin is diminished and suitable dosage adjustments must be observed. This is especially 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/1.73m2 at three months, compared to only 32 7 ml/min/1.73m2 at one week. By 12 months digoxin clearance of 88 ± 43 ml / min / 1.73m2 has been reported. Beyond the immediate newborn period, children generally require proportionally larger doses than adults on the basis of body weight and body surface area.
Renal impairment
The terminal elimination half-life of digoxin is prolonged in patients with impaired renal function, and in anuric patients may be of the order of 100 h.
Hepatic impairment
Hepatic impairment has little effect on digoxin clearance.
Elderly
Age-related declines in renal function in elderly patients can result in a lower rates of digoxin clearance than in younger subjects, with reported digoxin clearance rates in the elderly of 53 ml/min/1.73m2.
Gender
Digoxin clearance is 12% – 14% less in females than males and may need to be considered in dosing calculations.
Updated on 18 April 2017
Reasons for updating
- Change to section 1 - what the product is used for
- Change to section 2 - what you need to know - contraindications
- Change to section 2 - what you need to know - warnings and precautions
- Change to section 2 - use in children and adolescents
- Change to section 2 - interactions with other medicines, food or drink
- Change to section 2 - pregnancy, breast feeding and fertility
- Change to section 2 - driving and using machines
- Change to section 3 - use in children/adolescents
- Change to section 4 - possible side effects
- Change to section 4 - how to report a side effect
- Change to section 6 - date of revision
Updated on 10 April 2014
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- Change to section 7 - Marketing authorisation holder
- Change to section 10 - Date of revision of the text
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7 MARKETING AUTHORISATION HOLDER
12/13 Exchange Place
I.F.S.C Dublin 1
3016 Lake Drive,
Citywest Business Campus
Dublin 24
10 DATE OF REVISION OF THE TEXT
October April 20143
Updated on 08 April 2014
Reasons for updating
- Change to date of revision
- Change to MA holder contact details
Updated on 21 November 2013
Reasons for updating
- Change to section 10 - Date of revision of the text
- Change to section 4.3 - Contraindications
- Change to section 2 - Qualitative and quantitative composition
- Change to section 4.2 - Posology and method of administration
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 4.8 - Undesirable effects
- Change to section 4.9 - Overdose
- Change to section 5.2 - Pharmacokinetic properties
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2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Excipients with known effect:
Each tablet contains 95.525mg of Lactose Monohydrate.
For thea full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Tablets
4.1 Therapeutic Iindications
4.2 Posology and method of administration
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%.
Digoxin PG oral solution, 50 micrograms in 1 ml, is supplied with a graduated pipette and this should be used for measurement of all doses
Monitoring
Digoxin toxicity is more commonly associated with serum digoxin concentrations 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 clinical state together with the serum potassium level and thyroid function are important factors (see section 4.9 Overdose).
Dilution of digoxin injection:
Digoxin injection can be administered undiluted or diluted with a 4-fold or greater volume of diluent. The use of less than a 4-fold volume of diluent could lead to precipitation of digoxin. Digoxin injection, 250 micrograms per ml when diluted in the ratio of 1 to 250 (i.e. one 2 ml ampoule containing 500 micrograms added to 500ml of infusion solution) is known to be compatible with the following infusion solutions and stable for up to 48 h at room temperature (20 to 25°C).
Sodium chloride I.V. Infusion B.P., 0.9% w/v.
Sodium Chloride (0.18% w/v/) and Glucose (4% w/v) Intravenous Infusion, B.P.
Glucose I.V. Infusion, B.P., 5% w/v.
Dilution should be carried out either under full aseptic conditions or immediately before use. Any unused solution should be discarded.
Rapid oral loading:
Clinical response should be assessed before giving each additional dose (Ssee section 4.4 Special Ww warnings and precautions for use).
Slow oral loading
Parenteral loading
NOTE: for use 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 four to eight hours. An assessment of clinical response should be performed before giving each additional dose. Each dose should be given by i.v. infusion (see dilution of digoxin injection) over 10 to 20 mins.
Maintenance dose:
Preterm neonates less than 1.5 kg < 25 microgram /kg per 24 hours.
Maintenance dose:
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 above.
Dose rRecommendations in specific patient groups Renal Disorder or with Diuretic Therapy:
See section 4.4 Special w W arnings and p P recautions for u U se.
4.3 Contraindications
LANOXIN is contraindicated in intermittent complete heart block or second degree atrioventricular block, especially if there is a history of Stokes-Adams attacks.
4.4 Special warnings and precautions for use
Treatment with of digoxin should generally be avoided in patients with heart failure associated with cardiac amyloidosis.
Herbal preparations containing St. John’s Wort (Hypericum Pperforatum) should not be used while taking Lanoxin due to the risk of decreased plasma concentrations and reduced clinical effects of Lanoxin (see section 4.5 –Interaction with other medicinal products and other forms of interaction).
4.5 Interaction with other medicinal products and other forms of interaction
Calcium particularly if administered rapidly by the intravenous route, may produce serious arrhythmias in digitalised patients (see also section 4.4 Special wWarnings and Special Pprecautions for uUse).
Serum levels of digoxin may be INCREASED by concomitant administration of the following:
- amiodarone, flecainide, prazosin, propafenone, quinidine, spironolactone, macrolide, antibiotics e.g. erythromycin and clarithromycin, tetracycline (and possibly other antibiotics), gentamicin, itraconazole, quinine, trimethoprim, alprazolam, indomethacin, propantheline, nefazodone, atorvastatin, and ciycclosporin, epoprostenol (transient) and carvedilol.
Serum levels of digoxin may be REDUCED by concomitant administration of the following:
- antacids, some bulk laxatives, kaolin-pectin, acarbose, neomycin, penicillamine, rifampicin, some cytostatics, metoclopramide, sulfphasalazine, salbutamol, adrenaline, cholestyramine, phenytoin and St John's Wort (Hypericum perforatum)
Serum levels of digoxin can be reduced by concomitant use of the herbal preparations, St, John's Wort (Hypericum perforatum). This is due to induction of drug metabolising enzymes and/or P-glycoprotein by St. John's Wort. Herbal preparations containing St. John"'s Wort should therefore not be combined with Lanoxin.
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 (sSee section 5.2 Pharmacokinetics properties).
4.8 Undesirable effects
Adverse reactions are listed below by system organ class and frequency.
Frequenciesy are defined as: very common (³ >1/10), common (³>1/100 and <1/10), uncommon (³>1/1,000 and <1/100), rare (³>1/10,000 and <1/1,000), very rare (<1/10,000), including isolated reports.
Skin and subcutaneous tissue disorders
4.9 Overdose
Symptoms and sSigns
The symptoms and signs of toxicity are generally similar to those described in the Adverse reactions section but may be more frequent and can be more severe.
Signs and symptoms of digoxin toxicity become more frequent with levels above 2.0 nanograms/mL (2.56 nanomol/L) although there is considerable interindividual variation.
However, in deciding whether a patient’s symptoms are due to digoxin, the clinical state, together with serum electrolyte levels and thyroid function are important factors, (see section 4.2 Posology Dosage and method of administration).
Cardiac manifestations
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 block and AV disociation 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 sodiumpotassium (Na+-K+) pump. Hypokalaemia may contribute to toxicity (see section 4.4 Special warnings and Pprecautions for use).
5.2 Pharmacokinetic properties
Elimination
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 (Ssee section 4.5 Interaction with other medicinal products and other forms of interaction).
Following intravenous i.v. 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 cardioinactive 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. The terminal elimination half-life of digoxin in patients with normal renal function is 30 to 40 hours. It is prolonged in patients with impaired renal function, and in anuric patients may be of the order of 100 hours
Since most of the drug is bound to the tissues rather than circulating in the blood, digoxin is not effectively removed from the body during cardiopulmonary by-pass. Furthermore, only about 3% of a digoxin dose is removed from the body during 5 hours of haemodialysis.
Special patient populations
Neonates, infants and children up to 10 years of age
In the newborn period, renal clearance of digoxin is diminished and suitable dosage adjustments must be observed. This is especially pronounced in the premature infant since renal clearance reflects maturation of renal function. Digoxin clearance has been found to be 65.6 +/± 30ml/min/1.73m2 at 3 months, compared to only 32 +/± 7 ml/min/1.73m2 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.
Renal impairment
The terminal elimination half-life is prolonged in patients with impaired renal function, and in anuric patients may be of the order of 100 hours.
Since most of the drug is bound to the tissues rather than circulating in the blood, digoxin is not effectively removed from the body during cardiopulmonary by-pass. Furthermore, only about 3% of a digoxin dose is removed from the body during 5 hours of haemodialysis.[
10 DATE OF REVISION OF THE TEXT
December 2012 October 2013
Updated on 19 November 2013
Reasons for updating
- Change to, or new use for medicine
- Change to warnings or special precautions for use
- Change to storage instructions
- Change to side-effects
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- Change to further information section
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Updated on 28 January 2013
Reasons for updating
- Change to date of revision
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Updated on 14 January 2013
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- Change to section 3 - Pharmaceutical form
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There was a dembossing change from
Previous Round, biconvex tablets, coded Wellcome U3A and coloured blue.
Current tablets are; blue, round, biconvex debossed "DO6" on the one side and plain on the other side.
Updated on 27 May 2011
Reasons for updating
- Change to marketing authorisation holder
Updated on 05 May 2011
Reasons for updating
- Change to section 7 - Marketing authorisation holder
- Change to section 8 - MA number
- Change to section 10 - Date of revision of the text
- SPC retired pending re-submission
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Product ownership changed from GSK to Aspen
Updated on 18 March 2010
Reasons for updating
- Change to section 7 - Marketing authorisation holder
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Updated on 12 March 2010
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- Change to marketing authorisation holder
Updated on 29 September 2008
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
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4.4 Special Warnings and Special Precautions for Use
Addition of “However, the benefit of digoxin in patients with supraventricular arrhythmias is most evident at rest, less evident with exercise.”
4.5 Interaction with Other Medicaments and Other Forms of Interaction
Serum levels of digoxin may be INCREASED by concomitant administration of the following:
Addition of “epoprostenol (transient) and carvedilol.”
Updated on 19 June 2007
Reasons for updating
- Change to section 4.9 - Overdose
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4.9 Overdose
Signs and symptoms of digoxin toxicity become more frequent with levels above 2.0 nanograms/mL (2.56 nanomol/L) although there is considerable interindividual variation. However, in deciding whether a patient's symtoms are due to digoxin, the clinical state, together with serum electrolyte levels and thyroid function are important factors (see Dosage and Administration).
Updated on 12 March 2007
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- Improved electronic presentation
Updated on 07 March 2007
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- Change to section 1 - Name of medicinal product
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1. TRADE NAME OF THE MEDICINAL PRODUCT
Lanoxin PG 62.5 microgram Tablets
Updated on 05 July 2006
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.3 - Contraindications
- Change to section 4.8 - Undesirable effects
- Change to section 4.9 - Overdose
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4.2:
......Monitoring:
Serum concentrations of digoxin may be expressed in Conventional Units of nanograms/ml or SI Units of nanomol/l. To convert nanograms/ml to nanomol/l, multiply nanograms/ml by 1.28.
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. Several post hoc analyses of heart failure patients in the Digitalis Investigation Group trial suggest that the optimal trough difoxin 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 clinical state together with the serum potassium level and thyroid function are important factors (see Overdose). .......
......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 six hours apart, with approximately half the total dose given as the first dose.
Clinical response should be assessed before giving each additional dose (see Warnings and Precautions).
Slow oral loading:
In some patients, for example those with mild heart failure, digitalisation may be achieved more slowly with doses of 250 to 750 micrograms (0.25 to 0.75 mg) daily for one 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.
Parenteral Loading
NOTE: For use 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 four to eight hours. An assessment of clinical response should be performed before giving each additional dose. Each dose should be given by i.v. infusion (see Dilution of digoxin injection) over 10 to 20 mins.........
.....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 dose of 62.5 micrograms (0.0625 mg) daily or less may suffice. Conversely, some patients may require a higher dose......
4.3 Contraindications
.....Digoxin is contraindicated in patients known to be hypersensitive to digoxin, other digitalis glycosides or to any component of the preparation.
4.4 Warnings & precautions
...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.
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 .......
4.8 Undesirable effects
......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 |
4.9 Overdose
Symptoms and Signs
The symptoms and signs of toxicity are generally similar to those described in the Adverse Reactions 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 patient's symtoms are due to digoxin, the clinical state, together with serum electrolyte levels and thyroid function are important factors (see Dosage and Administration).
Adults
In adults without heart disease, clinical observation suggests that an overdose of digoxin of 10 to 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 disocciation 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 (see Warnings and Precautions).
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 verntricular 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.
Extracardiac manifestations
The frequent extracardiac manifestations similar to those seen in adults are gastrointestinal, CNS and visual. However, nausea and vomiting are not frequent in infants and small children.
In addition to the undesirable effects seen with recommended doses, weight loss in older age groups and failure to thrive in infants, abdominal pain due to mesenteric artery ischaemia, drowsiness and behavioural disturbances including psychotic manifestations have been reported in overdose.
Treatment
After recent ingestion, such as accidental or deliberate self-poisoning, the load available for absorption may be reduced by gastric lavage.
Patients with massive digitalis ingestion should receive large doses of activated charcoal to prevent absorption and bind digoxin in the gut during enteroenteric recirculation.
If hypokalaemia is present, it should be corrected with potassium supplements either orally or intravenously, depending on the urgency of the situation. In cases where a large amount of digoxin has been ingested hyperkalaemia may be present due to release of potassium from skeletal muscle. Before administering potassium in digoxin overdose the serum potassium level must be known.
Bradyarrhythmias may respond to atropine but temporary cardiac pacing may be required. Ventricular arrhythmias may respond to lignocaine or phenytoin.
Dialysis is not particularly effective in removing digoxin from the body in potentially life-threatening toxicity.
Digoxin-specific antibody Fab is a specific treatment for digoxin toxicity and is very effective. Rapid reversal of the complications that are associated with serious poisoning by digoxin, digitoxin and related glycosides has followed i.v. administration of digoxin-specific (ovine) antibody fragments (Fab). For details, consult the literature supplied with antibody fragments.
Updated on 05 July 2006
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.3 - Contraindications
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
- Change to section 4.9 - Overdose
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
4.2:
......Monitoring:
Serum concentrations of digoxin may be expressed in Conventional Units of nanograms/ml or SI Units of nanomol/l. To convert nanograms/ml to nanomol/l, multiply nanograms/ml by 1.28.
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. 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 clinical state together with the serum potassium level and thyroid function are important factors (see Overdose). .......
......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 six hours apart, with approximately half the total dose given as the first dose.
Clinical response should be assessed before giving each additional dose (see Warnings and Precautions).
Slow oral loading:
In some patients, for example those with mild heart failure, digitalisation may be achieved more slowly with doses of 250 to 750 micrograms (0.25 to 0.75 mg) daily for one 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.
Parenteral Loading
NOTE: For use 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 four to eight hours. An assessment of clinical response should be performed before giving each additional dose. Each dose should be given by i.v. infusion (see Dilution of digoxin injection) over 10 to 20 mins.........
.....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 dose of 62.5 micrograms (0.0625 mg) daily or less may suffice. Conversely, some patients may require a higher dose......
4.3 Contraindications
.....Digoxin is contraindicated in patients known to be hypersensitive to digoxin, other digitalis glycosides or to any component of the preparation.
4.4 Warnings & precautions
...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.
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 .......
4.8 Undesirable effects
......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 |
4.9 Overdose
Symptoms and Signs
The symptoms and signs of toxicity are generally similar to those described in the Adverse Reactions 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 patient's symtoms are due to digoxin, the clinical state, together with serum electrolyte levels and thyroid function are important factors (see Dosage and Administration).
Adults
In adults without heart disease, clinical observation suggests that an overdose of digoxin of 10 to 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 disocciation 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 (see Warnings and Precautions).
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 verntricular 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.
Extracardiac manifestations
The frequent extracardiac manifestations similar to those seen in adults are gastrointestinal, CNS and visual. However, nausea and vomiting are not frequent in infants and small children.
In addition to the undesirable effects seen with recommended doses, weight loss in older age groups and failure to thrive in infants, abdominal pain due to mesenteric artery ischaemia, drowsiness and behavioural disturbances including psychotic manifestations have been reported in overdose.
Treatment
After recent ingestion, such as accidental or deliberate self-poisoning, the load available for absorption may be reduced by gastric lavage.
Patients with massive digitalis ingestion should receive large doses of activated charcoal to prevent absorption and bind digoxin in the gut during enteroenteric recirculation.
If hypokalaemia is present, it should be corrected with potassium supplements either orally or intravenously, depending on the urgency of the situation. In cases where a large amount of digoxin has been ingested hyperkalaemia may be present due to release of potassium from skeletal muscle. Before administering potassium in digoxin overdose the serum potassium level must be known.
Bradyarrhythmias may respond to atropine but temporary cardiac pacing may be required. Ventricular arrhythmias may respond to lignocaine or phenytoin.
Dialysis is not particularly effective in removing digoxin from the body in potentially life-threatening toxicity.
Digoxin-specific antibody Fab is a specific treatment for digoxin toxicity and is very effective. Rapid reversal of the complications that are associated with serious poisoning by digoxin, digitoxin and related glycosides has followed i.v. administration of digoxin-specific (ovine) antibody fragments (Fab). For details, consult the literature supplied with antibody fragments.
Updated on 31 January 2006
Reasons for updating
- Improved electronic presentation
Updated on 18 January 2006
Reasons for updating
- Change to section 1 - Name of medicinal product
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 01 November 2005
Reasons for updating
- Improved electronic presentation
Updated on 26 May 2005
Reasons for updating
- New PIL for medicines.ie
Updated on 22 February 2005
Reasons for updating
- New SPC for medicines.ie
Legal category:Product subject to medical prescription which may be renewed (B)