Digoxin

Registered South African indications:

• Cardiac failure
• Supraventricular arrhythmias

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Complete heart block
• Second degree atrioventricular block
• Arrhythmias caused by cardiac glycoside intoxication
• Supravetricular arrhythmias associated with accessory atrioventricular pathway
• Ventricular tachycardia
• Ventricular fibrillation
• History of Stokes-Adams attacks
• Hypertrophic obstructive cardiomyopathy

Cautions

• Pregnancy
• Breastfeeding
• Severe renal impairment (loading dose when eGFR≤10ml/min/1.73m²)
• Moderate to severe renal impairment (maintenance dose when eGFR≤49ml/min/1.73m²)
• Elderly
• Sinus bradycardia
• Sinoatrial disorder
• Use of cardiac glycosides in the preceding 2 weeks
• Hypokalaemia
• Hypoxia
• Hypomagnesaemia
• Hypercalcaemia
• Thyroid disease
• Malabsorption syndrome
• Gastrointestinal reconstructions
• Elective direct current cardioversion
• Incomplete atrioventricular block
• Recent myocardial infarction
• Cardiac amyloidosis
• Myocarditis
• Constrictive pericarditis
• Beri-beri disease
• Severe respiratory disease
• Galactose intolerance
• Lapp lactase deficiency  
• Glucose-galactose malabsorption
• Fructose intolerance (liq)
• Sucrase-isomaltase insufficiency (liq)

Forms avail. in SA and covered in this monograph: inj, liq, tab

Chronic cardiac failure without supraventricular arrhythmia

• Oral (tab): 0.125-0.25mg, dly

Atrial fibrillation and flutter
- Loading

• Oral (tab, liq): Rapid oral loading: 0.75-1.5mg as single dose

OR

• Oral (tab, liq): Slow oral loading: 0.25-0.75mg dly for 1 week followed by appropriate maintenance dose

OR

• IV: Parenteral loading: 0.5-1mg; Initial: Half total dose, remaining portion of total dose divided and given at intervals of 4-8hrs; Each dose to be given over 10-20mins 

Atrial fibrillation and flutter
- Maintenance

• Oral (tab, liq): Maintenance based on percentage of peak body stores lost each day: Usual dose: 0.125-0.25mg, dly 

Dilution of injection: 2ml ampule containing 250μg/ml added to 500ml IV fluid (0,9% NaCl or 5% dextrose)

If cardiac glycosides were given in the 2 weeks prior, loading dose of digoxin will be less than recommended

Paed. forms avail. in SA and covered in this monograph: inj, liq, tab

Atrial fibrillation
Atrial flutter
Cardiac failure
- Loading

• Oral (tab, liq): Oral loading: 

• IV: Parenteral loading; Initial: Half total dose, remaining portion of total dose divided and given at intervals of 4-8hrs; Each dose to be given over 10-20mins 

Atrial fibrillation
Atrial flutter
Cardiac failure
- Maintenance 

• Preterm neonates: IV, Oral (tab, liq): 20% of 24hr loading dose, dly
• Term neonates and children up to 10 years: IV, Oral (tab, liq): 25% of 24hr loading dose, dly

Dose adjustment dependant on serum digoxin levels

If cardiac glycosides were given in the 2 weeks prior, loading dose of digoxin will be less than recommended

In the newborn period dosing adjustments must be made

Pregnancy

• Caution
• The use of digoxin in pregnancy is not contraindicated, although the dosage may be less predictable in pregnant than in non-pregnant women, with some requiring an increased dosage of digoxin during pregnancy. As with all medicines, use should be considered only when the expected clinical benefit of treatment to the mother outweighs any possible risk to the developing foetus
• Despite extensive antenatal exposure to digitalis preparations, no significant adverse effects have been observed in the foetus or neonate when maternal serum digoxin concentrations are maintained within the normal range. Although it has been speculated that a direct effect of digoxin on the myometrium may result in relative prematurity and low birthweight, a contributing role of the underlying cardiac disease cannot be excluded. Maternally-administered digoxin has been successfully used to treat foetal tachycardia and congestive heart failure
• Adverse foetal effects have been reported in mothers with digitalis toxicity

Breastfeeding

• Caution
• Although digoxin is excreted in breast milk, the quantities are minute and breastfeeding is not contraindicated

Renal Impairment

Loading dose

• eGFR ≥11- 89ml/min/1.73 m²: No dose adjustment recommended
• eGFR ≤10/min/1.73 m²/ESRD: Caution; dose adjustment recommended
  Reduce the loading dose by 50%; If a loading dose is necessary

Maintenance dose

• eGFR ≥50- 89ml/min/1.73 m²: No dose adjustment recommended
• eGFR ≤49ml/min/1.73 m²: Caution; dose adjustment recommended
  Digoxin plasma drug concentration monitoring (TDM) must be used as a guide for future dosing. Dose adjustment should be adopted according to the TDM levels

Hepatic Impairment

• No dose adjustment recommended

Elderly

• Caution; no dose adjustment recommended
  Initial; 0.0625mg, dly; titrate gradually to the therapeutic range; Periodic monitoring of digoxin plasma drug concentration (TDM) is recommended
  Consider 48hrly dosing in the following high-risk groups: Extreme elderly (> 80-year-old), co-existing renal or hepatic dysfunction and in hypothyroidism
  Watch for non-cardiac signs of digitalis toxicity in elderly: anorexia, blurred vision; unexplained confusion

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Dizziness
• Depression
• Fatigue
• Malaise
• Weakness
• Psychosis
• Apathy
• Confusion
• Headache

Cardiovascular Disorders

• Arrhythmia
• Conduction disturbances
• Bigeminy
• Trigeminy
• PR prolongation
• Sinus bradycardia
• Supra ventricular tachyarrhythmia
• Atrial tachycardia
• Junctional  tachycardia
• Ventricular arrhythmia
• Ventricular premature contraction
• ST segment depression

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Intestinal ischaemia
• Intestinal necrosis

Endocrine and Metabolic Disorders1

• Anorexia
• Gynaecomastia

Skin and Subcutaneous Tissue Disorders

• Urticaria

Immune, Blood and Lymphatic System Disorders

• Thrombocytopenia

Sensory Disorders

• Visual disturbances 

• Beta blockers
• Diuretics
• Lithium
• Corticosteroids
• Carbenoloxone
• Suxamethonium
• Calcium
• Alprazolam
• Amiodarone
• Flecainide
• Gentamicin
• Indomethacin 
• Itraconazole
• Prazosin
• Propafenone 
• Quinidine
• Quinine
• Spironolactone 
• Macrolide antibiotics
• Tetracycline 
• Trimethoprim 
• Propantheline
• Atorvastatin
• Ciclosporin
• Epoprostenol
• Carvedilol
• Adrenaline 
• Antacids
• Kaolin-pectin
• Bulk laxatives
• Colestyramine
• Acarbose
• Salbutamol
• Sulfasalazine 
• Neomycin
• Rifampicin
• Cytostatics 
• Phenytoin
• Metoclopramide 
• Penicillamine
• St John's wort 
• Verapamil
• Angiotensin converting enzyme inhibitors
• Calcium channel blockers

• Cardiac monitoring
• Electrolytes
• Digoxin levels

Drug levels

• Serum concentrations of digoxin may be expressed in ng/ml or nmol/L. To convert ng/ml to nmol/L, multiply ng/ml by 1.28
• Blood should be taken 6hrs or more after last dose
• Optimal trough level: 0.5-1.0ng/ml (0.64-1.28nmol/l)
• Toxicity > 2ng/ml (2.56nmol/l)

Tablet 0.25mg, Injection 0.25mg/ml - EML (Hospital)

All other formulations - Non-EML

Digoxin increases contractility of the myocardium by direct activity. It inhibits ATP, and 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. 

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. Increases in efferent vagal impulses result in reduced sympathetic tone and diminished impulse conduction rate through the atria and atrioventricular node. Thus, the major beneficial effect of digoxin is reduction of ventricular rate. Indirect cardiac contractility changes also result from changes in venous compliance brought about by the altered autonomic activity and by direct venous stimulation. 

Tablet 0.0625mg

• Lanoxin (Pharmacare) originator

Tablet 0.25mg 

• Lanoxin  (Pharmacare) originator
• Purgoxin (Pharmacare)

Elixir (per 1ml) 0.05mg

• Lanoxin PG (Pharmacare) originator

Injection (per ml) 0.25mg

• Lanoxin (Pharmacare) originator