Digoxin — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	0.005-0.01 mg/kg q12h (for dogs >20 kg); 0.01-0.02 mg/kg q12h (for dogs <20 kg)	q12h	Duration: Chronic therapy; adjust based on serum levels and clinical response Notes: Start with lower end of dose range; monitor serum digoxin levels (therapeutic range: 0.8-2.0 ng/mL).
Cat	PO	0.007-0.01 mg/kg q48h (or 0.01 mg/kg q24h in some cases)	q48h (or q24h)	Duration: Chronic therapy; adjust based on serum levels and clinical response Notes: Cats are more sensitive to digoxin; use lower doses and monitor closely. Therapeutic range: 0.8-2.0 ng/mL.
Horse	PO	0.01-0.02 mg/kg q12h (or 0.02 mg/kg q24h)	q12h or q24h	Duration: Chronic therapy; adjust based on serum levels and clinical response Notes: Monitor serum levels; therapeutic range: 0.8-2.0 ng/mL.
Cattle	PO	0.01-0.02 mg/kg q12h	q12h	Duration: Chronic therapy; adjust based on response Notes: Limited data; use with caution.

Clinical Indications & Species Uses

General Indications

Treatment of congestive heart failure
Control of ventricular rate in atrial fibrillation and atrial flutter

Dog (Canine)

Congestive heart failure (CHF) due to dilated cardiomyopathy or valvular disease
Atrial fibrillation (to control ventricular rate)
Supraventricular tachycardia (as an adjunctive therapy)

Cat (Feline)

Congestive heart failure (CHF) due to hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM)
Atrial fibrillation (to control ventricular rate)
Supraventricular tachycardia

Horse (Equine)

Atrial fibrillation (to control ventricular rate, especially in performance horses)
Congestive heart failure (rarely used)

Cattle (Bovine)

Congestive heart failure (rarely used)
Atrial fibrillation (rarely used)

Pharmacology & Mechanism of Action

Drug Class: Cardiac glycoside | Pharmacological Group: Inotropic agent, antiarrhythmic

Mechanism of Action: Digoxin inhibits the sodium-potassium ATPase (Na+/K+-ATPase) pump on the cell membrane of cardiac myocytes. This inhibition leads to an increase in intracellular sodium, which in turn reduces the activity of the sodium-calcium exchanger, resulting in increased intracellular calcium. The elevated intracellular calcium enhances cardiac contractility (positive inotropy). Additionally, digoxin increases vagal tone, which slows conduction through the atrioventricular (AV) node and reduces heart rate (negative chronotropy). It also has direct effects on the electrical properties of the heart, prolonging the effective refractory period of the AV node and reducing automaticity in the SA node.

Pharmacodynamics: Digoxin increases myocardial contractility, which is beneficial in heart failure. It also slows the ventricular response in atrial fibrillation and atrial flutter by enhancing vagal tone and prolonging AV nodal refractoriness. The therapeutic index is narrow, and the drug's effects are dose-dependent. At toxic levels, digoxin can cause arrhythmias due to increased automaticity and triggered activity. The drug's effects are more pronounced in patients with reduced renal function, as elimination is primarily renal.

⚡ Pharmacokinetics Summary

Absorption: Digoxin is well absorbed after oral administration in most species, but bioavailability varies by formulation. In dogs, the oral bioavailability of tablets is approximately 60-80%, while the elixir has higher bioavailability (about 75-85%). In cats, absorption is also good but may be variable. Food can affect absorption, so it is recommended to administer consistently with respect to meals.

Distribution: Digoxin is widely distributed throughout the body, with a large volume of distribution. It binds to tissues, particularly skeletal muscle and cardiac muscle. It crosses the placenta and is distributed into milk. Protein binding is moderate, approximately 20-30% in dogs and cats.

Metabolism: Digoxin undergoes minimal hepatic metabolism in most species. A small portion is metabolized in the liver, but the majority is excreted unchanged by the kidneys. In some species, such as the horse, metabolism may be more significant.

Excretion: Digoxin is primarily excreted unchanged in the urine via glomerular filtration and active tubular secretion. Renal clearance is proportional to glomerular filtration rate. In animals with renal impairment, the half-life is prolonged, and dosage adjustments are necessary. Biliary excretion and enterohepatic recirculation also occur to a minor extent.

Half-Life: Dog: 23-39 hours; Cat: 40-70 hours; Horse: 20-30 hours; Cattle: 10-20 hours (estimated).

Bioavailability: Oral tablets: 60-80% in dogs; elixir: 75-85% in dogs; oral solution: 70-85% in cats; oral paste: 60-70% in horses.

Protein Binding: 20-30% in dogs and cats; approximately 25% in horses.

Available Formulations & Strengths

Oral Tablet 0.125 mg, 0.25 mg, 0.5 mg (PO)

Oral Elixir 0.05 mg/mL (PO)

Oral Solution 0.25 mg/mL (PO)

Injectable Solution 0.25 mg/mL (IV, IM)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to digoxin or other cardiac glycosides
Ventricular fibrillation or ventricular tachycardia (unless due to heart failure)
Hypertrophic cardiomyopathy (HCM) in cats (may worsen outflow obstruction)
Severe renal impairment (use with extreme caution or avoid)
Concurrent use with calcium gluconate (IV) or other calcium-containing IV solutions
Hypokalemia, hypercalcemia, or hypomagnesemia (correct before therapy)

Warnings & Clinical Precautions:

Narrow therapeutic index; monitor serum digoxin levels regularly.
Use with caution in animals with renal impairment; adjust dose accordingly.
Use with caution in animals with electrolyte imbalances (hypokalemia, hypercalcemia, hypomagnesemia) as they increase digoxin toxicity.
Use with caution in animals with thyroid disease (hypothyroidism may increase sensitivity).
Use with caution in animals with hepatic disease (may affect metabolism).
Monitor for signs of toxicity (anorexia, vomiting, diarrhea, arrhythmias).
In cats, use with extreme caution due to narrow margin of safety.
In horses, monitor for gastrointestinal signs (colic) and arrhythmias.
Do not use in animals with known hypersensitivity.
Avoid concurrent use with drugs that increase digoxin levels (e.g., quinidine, verapamil, amiodarone).

Adverse Effects & Reactions

Common:

Anorexia
Vomiting
Diarrhea
Lethargy
Weight loss

Serious / Severe:

Cardiac arrhythmias (e.g., AV block, ventricular tachycardia, atrial fibrillation)
Heart block
Hyperkalemia (in overdose)
Seizures (rare)
Death

Rare:

Gynecomastia (in males)
Allergic reactions
Thrombocytopenia

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Quinidine	Increases digoxin serum levels by decreasing clearance and displacing from tissue binding sites; risk of toxicity.	High
Verapamil	Increases digoxin serum levels by decreasing renal and non-renal clearance; risk of toxicity.	High
Amiodarone	Increases digoxin serum levels by inhibiting P-glycoprotein and renal clearance; risk of toxicity.	High
Diuretics (e.g., furosemide)	May cause hypokalemia, which increases the risk of digoxin toxicity.	Moderate
Corticosteroids	May cause hypokalemia, increasing digoxin toxicity risk.	Moderate
Antacids (aluminum/magnesium)	May reduce absorption of oral digoxin.	Mild
Kaolin-pectin	May reduce absorption of oral digoxin.	Mild
Succinylcholine	May increase risk of arrhythmias due to hyperkalemia.	Moderate
Beta-blockers (e.g., propranolol)	Additive negative chronotropic effects; may cause bradycardia or heart block.	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

Gastrointestinal signs (anorexia, vomiting, diarrhea)
Cardiac arrhythmias (bradycardia, AV block, ventricular tachycardia, fibrillation)
Hyperkalemia
Lethargy, weakness
Seizures (in severe cases)
Death

Emergency Treatment Protocol: Treatment of digoxin overdose includes: 1) Discontinue digoxin immediately. 2) Administer activated charcoal if ingestion is recent (within 1-2 hours). 3) Correct electrolyte imbalances (potassium, magnesium, calcium). 4) For severe bradycardia or heart block, administer atropine or temporary pacing. 5) For ventricular arrhythmias, use lidocaine or phenytoin (avoid quinidine and procainamide). 6) Digoxin-specific Fab fragments (Digibind) are the definitive antidote and should be used in severe cases. 7) Provide supportive care including IV fluids and cardiac monitoring.

Food Animal Withdrawal Times

🥩 Meat: 30 days🥛 Milk: 7 days

Withdrawal times are estimates; consult regulatory guidelines for specific region. Digoxin is not commonly used in food animals, and extra-label use requires extended withdrawal periods.

Storage, Handling & Regulatory Information

Storage Temperature: Store at room temperature (15-30°C) in a tight, light-resistant container.

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Protect from moisture and light. Keep out of reach of children and animals.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in dogs and cats (oral tablets and elixir). Not approved for horses, cattle, or other species; use is extra-label.

Extra-Label (Off-Label) Use: In the US, extra-label use of digoxin in food animals is prohibited or requires a prolonged withdrawal period under AMDUCA. Use in food animals should be under veterinary supervision with appropriate withdrawal times.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Digoxin is a valuable drug for managing congestive heart failure and controlling ventricular rate in atrial fibrillation. However, its narrow therapeutic index necessitates careful dosing and monitoring. Serum digoxin levels should be measured 6-8 hours after administration (trough levels) and maintained within the therapeutic range (0.8-2.0 ng/mL). Renal function and electrolyte status should be assessed before and during therapy. In cats, lower doses are required due to longer half-life and increased sensitivity. In horses, digoxin is primarily used for atrial fibrillation, but its use is limited by variable absorption and the need for careful monitoring. Always consider alternative therapies (e.g., ACE inhibitors, pimobendan) for heart failure, and use digoxin as an adjunct when indicated. Client education is crucial to recognize signs of toxicity and to ensure compliance with dosing schedules.

References & Literature

📚 Plumb's Veterinary Drug Handbook
📚 Papich Veterinary Pharmacology and Therapeutics
📚 Compendium of Veterinary Products (CVP)