Digoxin 

Crystals, clear to white, or crystalline powder, white, with a bitter taste. (B263)

• Diluted alcohol: slightly soluble. (B263)
• 40% propylene glycol solution: very slightly soluble. (B263)

• Store tablets, capsules, elixir and injectable forms at room temperature (15 - 30 °C); protect from light. (B263)
• Note: stable at pH 5-8 but hydrolysed at pH less than 3. (B263)

Physical compatibilities

Reported to be physically compatible with: 

• Injectable product is compatible with most commercially available IV solutions, including lactated Ringer's, 5% dextrose, and normal (0.9%) saline. (B263)
• Note: "To prevent the possibility of precipitation occurring, one manufacturer (Glaxo Wellcome) recommends that the injection be diluted by a volume at least 4 times with either sterile water, D5W, or normal saline." (B263)
• Demonstrated physical compatibility with "bretylium tosylate, cimetidine HCl, lidocaine HCl, and verapamil HCl." (B263)

Reported to be physically incompatible with: 

• The injectable product is incompatible with dobutamine HCl, acids and alkalis. (B263)
• Mixing with other medications is not recommended by the manufacturer. (B263)

Note: Physical compatibility is affected by factors such as concentration, pH, temperature and diluents; specialized references should be consulted for more specific information. (B263)

Associated Techniques

Digitalis glycoside general: several electrocardiac effects, including: "decreased conduction velocity through the AV node, and prolonged effective refractory period (ERP). They may also increase the PR interval, decrease the QT interval and cause ST segment depression." (B263)

• For the control of supraventricular tachycardias, particularly atrial fibrillation. (B373.4.w4)
• For the treatment of congestive heart failure associated with primary or secondary myocardial failure, particularly dilated cardiomyopathy (but not for CHF due to valvular insufficiency or intracardiac shunts, unless these conditions have led to secondary tachycardia or myocardial insufficiency. (B373.4.w4)

• Absorbed in the small intestine. (B263)
  • Absorption may be delayed by the presence of food, but the extent of absorption is unchanged. (B263)
  • Peak serum levels following oral elixir usually within 45-60 minutes; after oral tablet usually about 90 minutes. (B263)
  • Some entero-hepatic recirculation occurs. (B263)
• Note: following an initial oral dose, peak effects may be seen at six to eight hours after administration. (B263)
• Note: Bioavailability is affected by the gastro-intestinal flora as well as by the lipid solubility of the particular preparation used, therefore there is individual variation in response to a given dose, as well as variable responses to different preparations. (B373.4.w4)

• Widely distributed. (B263)
  • Highest levels are in the kidneys, heart, intestine, stomach, liver, skeletal muscle. (B263)
  • Lowest levels in the brain and in plasma. (B263)
  • Note: Only small amounts are distributed to fat, therefore doses based on total, rather than lean, body mass may result in overdosage in obese individuals. (B263)

• Mainly renal as unchanged drug: by both glomerular filtration and tubular secretion. (B263, B373.4.w4)
• Slightly metabolised. (B263)

• In dogs:
  • 14.4 - 56 hours reported. (B263)
  • Plasma half life of 22 - 55 hours. (B373.4.w4)
• In cats: 33.3 +/- 9.5 hours. (B263)
• In sheep: 7.15 hours. (B263)
• In horses:
  • 16.9 - 23.2 hours. (B263)
  • Plasma half-life 12 - 48 hours. (B373.4.w4)
• In cattle: 7.8 hours. (B263)

Note: reduced elimination rate in individuals with significant renal disease. (B263, B373.4.w4)

• Absorption of digoxin from the gastro-intestinal tract may be decreased by "Antacids, cimetidine, metoclopramide, neomycin (oral), chemotherapy agents (e.g., cyclophosphamide, doxorubicin, vinca alkaloids, cytarabine)." (B263)
• Serum level may be increased, elimination rate decreased, or toxic effects enhanced, by: "diazepam, quinidine, anticholinergics, succinylcholine, verapamil, tetracycline and erythromycin." (B263)
• Note: Digoxin dosage may need to be adjusted in individuals receiving thyroid replacement therapy. (B263)
• Serum levels of digoxin may be decreased by penicillamine. (B263)
• Drugs that can affect electrolyte balance can alter the efficacy or enhance the toxic effects of
  digoxin: (B263)
  • The patient may have an increased risk of digoxin toxicity if also receiving diuretics such as furosemide and thiazides. (B263)
  • The patient may have an increased risk of digoxin toxicity if recieving drugs which can deplete body potassium, including amphotericin B, glucocorticoids, ACTH, laxatives, sodium polystyrene sulfonate, or drugs which decrease extracellular potassium, such as glucagon, high dose intravenous dextrose or dextrose/insulin infusions. (B263)
• Toxic effects of digoxin may be either decreased or increased in individuals also receiving spironolactone. (B263)
• Note: When used in the treatment of atrial fibrillation or flutter before administration of an antiarrhythmic agent which has anticholinergic activity, such as quinidine, procainamide or disopyramide, digitalis glycosides will reduce, although not totally, the increased ventricular rates that the anti-arrhythmic agent may produce. (B263)

Note: 

• Avoid changing the dose form of orally-administered digoxin. (B373.4.w4)
• If changing from tablet to elixir, reduce the dose by 25%. (B373.4.w4)
• In maintenance therapy, allow six to eight days for any effect of a change in dose form to become evident. B373.4.w4

• Orally, 220 micrograms per m² twice daily: in small dogs, 10 micrograms per kg twice daily, in large dogs 5 micrograms per kg twice daily. For Dobermanns, further reduce the dosage. (B373.4.w4)

Cats: 

• Orally, 7-10 micrograms/kg on alternate days or 4 micrograms/kg daily. Use the elixir. (B373.4.w4)

Horses: 

• Orally, initial dose of 20 micrograms per kg, followed by 20 micrograms per kg daily in two divided doses. 
• Intravenously, 2.5 - 5.0 micrograms per kg twice daily.

Lagomorphs - Oryctolagus cuniculus domesticus - Domestic rabbit:

• 0.005 - 0.01 mg/kg orally every 24 - 48 hours. (B546)
• 0.003 - 0.03 mg/kg orally every 12-48 hours. In the treatment of atrial fibrillation, and mitral and bicuspid valve regurgitation. (J15.27.w1)
• 0.005 - 0.02 mg/kg orally daily or every other day. (B601.10.w10); 0.003 - 0.03 mg/kg orally every 12-48 hours. In the treatment of dilated cardiomyopathy. (J15.27.w1)
• 0.005 - 0.01 mg/kg orally every 24 - 48 hours. (B602.41.w41)

Ferrets - Mustela putorius furo - Ferret:

• 0.005 - 0.01 mg/kg orally every 12 - 24 hours. (B602.41.w41, B631.21.w21) For the treatment of dilated cardiomyopathy. (B631.21.w21)
• 0.005 - 0.01 mg/kg orally (elixir) once or twice daily for maintenance; monitoring of blood levels is recommended. (B626.App.w22, J213.3.w1)
• Lanoxin tablets 1/8 of a 0.125 mg tablet, in solution, once every other day. (B626.App.w22, B631.21.w21)

Great Apes

• Adult Pan troglodytes - Chimpanzee: 0.005 - 0.01 mg/kg orally twice daily; 0.005 - 0.01 mg/kg intravenously as required. (W768.Jun2012.w1)

• This drug has a narrow therapeutic index and significant intraindividual pharmacokinetic variation, therefore monitoring of serum levels of digoxin is strongly recommended. If no loading dose is given, levels should be monitored after six days of treatment, to allow steady state concentration to be reached. (B263)
• Suggested target serum concentration 0.8 - 2.4 ng/mL, preferably under 1.5 ng/mL to avoid toxicity. (B373.4.w4)
  • If the target therapeutic effect (reduced heart rate) is reached with serum concentrations under 0.8 ng/mL, this is acceptable. (B373.4.w4)
• In dogs: suggested therapeutic levels in serum of 0.9 - 3.0 ng/mL (B263)
• In cats: suggested therapeutic levels in serum of 0.9 - 2.0 ng/mL (B263)
• Other species: as a guideline, 0.5 - 2.0 ng/mL (B263)
• Note: 
  • For some atrial arrhythmias it may be necessary to reach levels at the high end of the therapeutic range; higher incidence of adverse effects may occur at these levels. (B263)
  • Usually it is recommended that a trough level should be reached just before the next dose or at least eight hours after the previous dose. (B263)

Other parameters:

• Weight and appetite.
• Heart rate and ECG changes
• Serum electrolyte levels
• Clinical efficacy in reducing the signs of congestive heart failure: improved perfusion, decreased oedema, increased blood oxygen level.

(B263)

• Contraindicated in:
  • Individuals with ventricular fibrillation or in digitalis intoxication. (B263)
  • Individuals with hypertrophic myocardial disorders.(B373.4.w4)
  • Individuals with severe dysrhythmias, including bradycardia. (B373.4.w4)
• Use with extreme caution in:
  • Individuals with glomerulonephritis and heart failure, idiopathic hypertrophic subaortic stenosis (IHSS). (B263)
• Use with caution in individuals with: 
  • "severe pulmonary disease, hypoxia, acute myocarditis, myxedema, or acute myocardial infarction, frequent ventricular premature contractions, ventricular tachycardias, chronic constrictive pericarditis or incomplete AV block." (B263)
    • Cardiac glycosides may be used in individuals with a stable, complete atrioventricular block or severe bradycardia with heart failure, so long as the block was not due to the cardiac glycoside. (B263)
  • Individuals with increased carotid sinus sensitivity, since digitalis glycosides may increase vagal tone. (B263)
  • Individuals with renal disease; monitor serum levels. (B263)
    • Reduce dose in individuals with reduced renal perfusion: for every 50% increase in plasma urea concentration, reduce the dose by 50%, then measure serum levels of digoxin and titrate subsequent doses based on the this. (B373.4.w4)
• Use with care in cats. (B373.4.w4)
• Note: 
  • In individuals with atrial fibrillation, stop administration of digitalis glycosides for one to two days before elective cardioversions. Do not attempt cardioversion in individuals with signs of digitalis toxicity. (B263)
  • Smaller dosages may be needed in individuals with hypernatraemia, hyokalaemia, hypercalcaemia, or which are either hypothyroid or hyperthyroid. (B263)
  • Take care not to confuse the different available concentrations of elixir. (B263)

(B263, B373.4.w4)

Note: 

• Species differ in their sensitivity to the toxic effects of digoxin: cats are more sensitive than dogs. (B263)
• Susceptibility to toxic effects is increased by hypothyroidism, renal insufficiency, obesity, hypokalaemia due to prolonged diuretic therapy, and in aged individuals. (B373.4.w4)

Signs of toxicity

• Cardiac effects are usually seen first. These may include many types of cardiac arrhythmia (e.g. complete or incomplete hearts block, bigeminy, ST segment changes, multifocal premature ventricular contractions or paroxysmal ventricular or atrial tachycardias with block.
  • It can be difficult to determine whether worsening signs are due to toxicity or deterioration of heart disease; serum levels should be checked or digoxin treatment temporarily suspended if there is any risk the signs may be due to toxicity.
  • Reduced cardiac output due to overdose may lead to hypoperfusion and thereby renal dysfunction. (B373.4.w4)
• Extracardiac symptoms include depression and gastro-intestinal upset (e.g. anorexia, weight loss, diarrhoea and vomiting). (B263, B373.4.w4) 
  • With intravenous injection, vomiting may occur; this should not be a cause for alarm. (B263)
• In humans, ocular and neurological signs may occur; these are not prevalent (or not detected) in animals.

(B263)

Warnings

• Warn owners to stop administration is signs of toxicity such as depression and gastro-intestinal effects occur. (B373.4.w4)

• Treatment of chronic digoxin toxicity: usually, temporarily cease administration of the drug. (B263)

Acute toxic dose:

• In dogs, 0.177 mg/kg reported as a toxic dose. (B263)
• Treatment: 
  • Reduce absorption: (B263)
    • If the drug has been ingested, and if cardiotoxic or neurological signs such as seizures have not yet occurred, consider gastric emptying, then administration of activated charcoal to decrease absorption of the drug. Repeated administration of charcoal may be useful, even some time after ingestion, since absorption is slow and some entero-hepatic recirculation takes place. 
    • If available (not generally in veterinary practices) consider giving colestipol, cholestyramine or another anion-exchange resin, to reduce absorption and enterohepatic recirculation.
  • Give supportive and symptomatic treatment as indicated by cardiotoxic signs: (B263)
    • Correct any acid-base, fluid and electrolye imbalances, and treat for hypoxia as require.
    • Preferably monitor serum electrolyte concentrations, arterial blood gases, cardiac function by ECG, and drug levels.
    • If arrhythmias induced by toxicity are life-threatening, it may be necessary to treat with antiarrhthmic agents: phenytoin, lidocaine or propranolol.
    • For sinus bradycardia, sino-atrial arrest, second or third degree atrioventricular block, treatment with atropine may be used. 
  • Specific treatment: Digoxin immune Fab. This is produced from specific digoxin antibodies from sheep; it binds directly to the drug, inactivating it. However, it is extremely expensive and there is only very limited experience with its use in veterinary practice. (B263)

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