Drugs List

Therapeutic Indications

Uses

Cardiac failure with atrial fibrillation
Chronic cardiac failure with predominant systolic dysfunction
Supraventricular arrhythmias - prophylaxis and treatment

Contraindications

Cardiac glycoside toxicity
Hereditary fructose intolerance
History of Stokes-Adams attacks
Hypertrophic obstructive cardiomyopathy without AF or heart failure
Intermittent complete heart block
Myocarditis
Second degree atrioventricular block
Ventricular fibrillation
Ventricular tachycardia

Precautions and Warnings

Cardiac glycosides given two weeks prior to therapy
Elderly
Atrial tachycardia with atrioventricular block
Breastfeeding
Cardiac amyloidosis
Constrictive pericarditis
Glucose-galactose malabsorption syndrome
Hypokalaemia
Hypomagnesaemia
Hypoxia
Malabsorption syndrome
Non-paced sinus node dysfunction
Pregnancy
Prior to electrical cardioversion
Recent myocardial infarction
Renal impairment
Severe hypercalcaemia
Severe respiratory disease
Supraventricular arrhythmias secondary to Wolff-Parkinson-White syndrome
Thyroid dysfunction

Patients with beri beri heart disease may not benefit from treatment
Advise ability to drive/operate machinery may be affected by side effects
Some formulations contain sucrose
Do not dilute the oral liquid
Monitor renal function
Monitor serum electrolytes
Narrow therapeutic range - monitoring levels useful to assess toxicity
To monitor serum levels, take blood at least 6 hours after dose
Arrhythmias precipitated by digoxin may resemble those for which drug used
May affect results of some laboratory tests
May cause changes to ECG
Withdrawal of therapy: caution with concurrent ACE inhibitors/diuretics
Withhold therapy for 24 hours before elective direct current cardioversion
Advise patient not to take St John's wort concurrently
Advise patient to take at separate time of day to antacid preparations

Determination of 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.

Administering digoxin to a patient with thyroid disease requires care. Initial and maintenance doses of digoxin 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.

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. When incomplete atrioventricular block already exists, however, 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 contraindicated. 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. Also the use of inotropic drugs in this situation may result in the increase of myocardial oxygen demand and ischaemia for some patients. There may also be an associated higher risk of death.

Although many patients with chronic congestive cardiac failure benefit from acute administration of digoxin, there are some in which it does not lead to constant, marked or lasting haemodynamic improvement. It is therefore important to evaluate the response of each patient individually when digoxin is continued long term.

Patients with malabsorption syndrome or gastrointestinal reconstruction may require increased doses of digoxin.

Advise patient to avoid taking antacids or bulk laxatives at the same time of the day as digoxin to avoid reducing serum digoxin levels.

Pregnancy and Lactation

Pregnancy

Use digoxin with caution in pregnancy.

The use of digoxin in pregnancy is not contraindicated, 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. No reports linking digitalis, or the various digitalis glycosides with congenital defects have been located, and animal studies have failed to show a teratogenic effect. The passage of digoxin to the foetus has been shown to be rapid. It was found that the amount of digoxin recovered from the foetus was dependent on length of gestation by one group of investigators.
Digoxin has been used during all stages of pregnancy for both maternal and foetal indications (such as supraventricular tachycardia and congestive heart failure) without causing foetal harm. It appears that the myocardial sensitivity in the foetus seems to be less than it is in adults (Schaefer, 2007). Direct administration of digoxin via periodic IM injections to the foetus has been used to treat supraventricular tachycardia when indirect therapy via the mother failed to control the arrhythmia. Schaefer (2007) concludes that digitalis glycosides can be used during pregnancy, as there have been no reports linking them with congenital malformations, and they are indicated for some kinds of maternal and foetal tachycardia and for some instances of chronic cardiac failure. However, foetal toxicity has been reported which resulted in neonatal death after maternal overdose. The mother, who was in her 8th month of pregnancy, took an estimated 8.9 mg of digitoxin as a single dose. Delivery occurred 4 days later and the baby demonstrated digitalis cardiac effects until death at age 3 days from prolonged intrauterine anoxia.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use digoxin with caution in breastfeeding.

Digoxin is excreted into breast milk. Digoxin milk: plasma ratios vary from 0.6 to 0.9. No adverse effects in the nursing infant have been reported.

LactMed state that because of the low levels of digoxin present in breast milk, the amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants. If the mother is to receive digoxin intravenously, avoidance of breastfeeding for 2 hours after the dose will lessen the dose the infant receives. Schaefer (2007) states that digoxin is no cause for concern during breastfeeding.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Anorexia
Apathy
Arrhythmias
Atrial tachycardia
Atrioventricular block
Atrioventricular junctional tachycardia
Bigeminy
Bradycardia
CNS disturbances
Conduction disturbances
Confusion
Depression
Diarrhoea
Dizziness
Eosinophilia
Fatigue
Gynaecomastia
Headache
Intestinal ischaemia
Intestinal necrosis
Malaise
Nausea
Premature ventricular contractions
Prolongation of PR interval
Psychosis
Rash
ST depression
Supraventricular tachycardia
Thrombocytopenia
Trigeminy
Ventricular arrhythmias
Visual disturbances
Vomiting
Weakness

Presentation

Oral solution containing digoxin.

Drugs List

Therapeutic Indications

Uses

Cardiac failure with atrial fibrillation
Chronic cardiac failure with predominant systolic dysfunction
Supraventricular arrhythmias - prophylaxis and treatment

Dosage

The dose of digoxin for each patient has to be tailored individually according to age, lean body weight and renal function.

If cardiac glycosides have been given in the 2 weeks preceding digoxin therapy, the optimum loading dose of digoxin will less than recommendations below.

Adults

Children

Neonates

Patients with Renal Impairment

Therapeutic Drug Monitoring

Digoxin Bioavailability
The difference in bioavailability between injectable digoxin 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 Serum Levels
Contact local therapeutic drug monitoring service for specific local digoxin guidelines.

Serum concentrations of digoxin may be expressed in conventional units of nanograms/ml (ng/ml) or SI units of nanomol/l (nmol/l). To convert ng/ml to nmol/l, multiply ng/ml by 1.28.

Serum concentrations of digoxin can be determined by radio immunoassay. Blood should be taken 6 hours or more after last dose. Several post hoc analyses of heart failure patients in the digitalis investigation group trial suggests that the optimal trough digoxin serum level may be 0.5 nanograms per ml to 1 nanograms per ml. This is equivalent to 0.64 nanoMol/litre to 1.28 nanoMol/litre.

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 patients symptoms are due to digoxin, the patient's clinical state together with the serum potassium level and thyroid function are important factors.

Contraindications

Cardiac glycoside toxicity
Hereditary fructose intolerance
History of Stokes-Adams attacks
Hypertrophic obstructive cardiomyopathy without AF or heart failure
Intermittent complete heart block
Myocarditis
Second degree atrioventricular block
Ventricular fibrillation
Ventricular tachycardia

Precautions and Warnings

Cardiac glycosides given two weeks prior to therapy
Elderly
Atrial tachycardia with atrioventricular block
Breastfeeding
Cardiac amyloidosis
Constrictive pericarditis
Glucose-galactose malabsorption syndrome
Hypokalaemia
Hypomagnesaemia
Hypoxia
Malabsorption syndrome
Non-paced sinus node dysfunction
Pregnancy
Prior to electrical cardioversion
Recent myocardial infarction
Renal impairment
Severe hypercalcaemia
Severe respiratory disease
Supraventricular arrhythmias secondary to Wolff-Parkinson-White syndrome
Thyroid dysfunction

Patients with beri beri heart disease may not benefit from treatment
Advise ability to drive/operate machinery may be affected by side effects
Some formulations contain sucrose
Do not dilute the oral liquid
Monitor renal function
Monitor serum electrolytes
Narrow therapeutic range - monitoring levels useful to assess toxicity
To monitor serum levels, take blood at least 6 hours after dose
Arrhythmias precipitated by digoxin may resemble those for which drug used
May affect results of some laboratory tests
May cause changes to ECG
Withdrawal of therapy: caution with concurrent ACE inhibitors/diuretics
Withhold therapy for 24 hours before elective direct current cardioversion
Advise patient not to take St John's wort concurrently
Advise patient to take at separate time of day to antacid preparations

Determination of 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.

Administering digoxin to a patient with thyroid disease requires care. Initial and maintenance doses of digoxin 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.

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. When incomplete atrioventricular block already exists, however, 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 contraindicated. 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. Also the use of inotropic drugs in this situation may result in the increase of myocardial oxygen demand and ischaemia for some patients. There may also be an associated higher risk of death.

Although many patients with chronic congestive cardiac failure benefit from acute administration of digoxin, there are some in which it does not lead to constant, marked or lasting haemodynamic improvement. It is therefore important to evaluate the response of each patient individually when digoxin is continued long term.

Patients with malabsorption syndrome or gastrointestinal reconstruction may require increased doses of digoxin.

Advise patient to avoid taking antacids or bulk laxatives at the same time of the day as digoxin to avoid reducing serum digoxin levels.

Pregnancy and Lactation

Pregnancy

Use digoxin with caution in pregnancy.

The use of digoxin in pregnancy is not contraindicated, 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. No reports linking digitalis, or the various digitalis glycosides with congenital defects have been located, and animal studies have failed to show a teratogenic effect. The passage of digoxin to the foetus has been shown to be rapid. It was found that the amount of digoxin recovered from the foetus was dependent on length of gestation by one group of investigators.
Digoxin has been used during all stages of pregnancy for both maternal and foetal indications (such as supraventricular tachycardia and congestive heart failure) without causing foetal harm. It appears that the myocardial sensitivity in the foetus seems to be less than it is in adults (Schaefer, 2007). Direct administration of digoxin via periodic IM injections to the foetus has been used to treat supraventricular tachycardia when indirect therapy via the mother failed to control the arrhythmia. Schaefer (2007) concludes that digitalis glycosides can be used during pregnancy, as there have been no reports linking them with congenital malformations, and they are indicated for some kinds of maternal and foetal tachycardia and for some instances of chronic cardiac failure. However, foetal toxicity has been reported which resulted in neonatal death after maternal overdose. The mother, who was in her 8th month of pregnancy, took an estimated 8.9 mg of digitoxin as a single dose. Delivery occurred 4 days later and the baby demonstrated digitalis cardiac effects until death at age 3 days from prolonged intrauterine anoxia.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use digoxin with caution in breastfeeding.

Digoxin is excreted into breast milk. Digoxin milk: plasma ratios vary from 0.6 to 0.9. No adverse effects in the nursing infant have been reported.

LactMed state that because of the low levels of digoxin present in breast milk, the amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants. If the mother is to receive digoxin intravenously, avoidance of breastfeeding for 2 hours after the dose will lessen the dose the infant receives. Schaefer (2007) states that digoxin is no cause for concern during breastfeeding.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Anorexia
Apathy
Arrhythmias
Atrial tachycardia
Atrioventricular block
Atrioventricular junctional tachycardia
Bigeminy
Bradycardia
CNS disturbances
Conduction disturbances
Confusion
Depression
Diarrhoea
Dizziness
Eosinophilia
Fatigue
Gynaecomastia
Headache
Intestinal ischaemia
Intestinal necrosis
Malaise
Nausea
Premature ventricular contractions
Prolongation of PR interval
Psychosis
Rash
ST depression
Supraventricular tachycardia
Thrombocytopenia
Trigeminy
Ventricular arrhythmias
Visual disturbances
Vomiting
Weakness

Effects on Laboratory Tests

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.

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: November 2015

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Martindale: The Complete Drug Reference (online) London: Brayfield A (ed). Pharmaceutical Press Accessed on 12 November 2015.

Summary of Product Characteristics: Lanoxin PG Elixir. Aspen. Revised November 2013.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 27 June 2017

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/download.txt
Digoxin Last revised: 7 September, 2013
Last accessed: 12 November, 2015