What is digoxin (digitalis glycoside) toxicity?

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From the Guidelines

Digoxin toxicity is a life-threatening condition that requires immediate medical attention, and the administration of digoxin-specific antibody fragments (digoxin-Fab) is the recommended treatment for severe cases, as stated in the 2023 American Heart Association guidelines 1.

Causes and Symptoms of Digoxin Toxicity

Digoxin toxicity occurs when levels of the cardiac medication digoxin become too high in the bloodstream, causing harmful effects. This can happen from taking too much digoxin, having reduced kidney function, or from drug interactions that increase digoxin levels. Symptoms range from mild to severe and include:

  • Nausea
  • Vomiting
  • Diarrhea
  • Visual disturbances (seeing yellow halos around objects)
  • Confusion
  • Irregular heartbeat
  • Potentially life-threatening cardiac arrhythmias

Diagnosis and Treatment of Digoxin Toxicity

Diagnosis involves measuring serum digoxin levels, with toxicity typically occurring at levels above 2 ng/mL, though symptoms can appear at lower levels in some patients. Treatment depends on severity and may include:

  • Stopping digoxin
  • Administering activated charcoal for recent overdoses
  • Correcting electrolyte imbalances (especially potassium)
  • Using digoxin-specific antibody fragments (Digibind or DigiFab) in severe cases, as recommended by the 2023 American Heart Association guidelines 1 According to the guidelines, administration of digoxin-Fab is recommended for digoxin or digitoxin poisoning, with a Class of Recommendation (COR) of 1 and a Level of Evidence (LOE) of B-NR 1. Patients taking digoxin should have regular monitoring of drug levels and kidney function, be aware of potential drug interactions, and report any symptoms promptly to their healthcare provider. Certain medications like amiodarone, verapamil, and some antibiotics can increase digoxin levels and should be used cautiously in patients taking this medication. The 2020 American Heart Association guidelines also support the use of antidigoxin Fab fragments for the treatment of serious cardiac arrhythmias induced by digitalis and other cardiac glycoside overdose 1. Additionally, the 2010 American Heart Association guidelines provide guidance on the administration of antidigoxin Fab antibodies, including the dose and timing of administration 1.

From the FDA Drug Label

OVERDOSAGE Digoxin should be temporarily discontinued until the adverse reaction resolves. Treatment of Adverse Reactions Produced by Overdosage: Withdrawal of digoxin may be all that is required to treat the adverse reaction. Manifestations of life-threatening toxicity include ventricular tachycardia or ventricular fibrillation, or progressive bradyarrhythmias, or heart block The administration of more than 10 mg of digoxin in a previously healthy adult, or more than 4 mg in a previously healthy child, or a steady-state serum concentration greater than 10 ng/mL often results in cardiac arrest.

Digoxin toxicity is a condition that occurs when there is an excessive amount of digoxin in the body, leading to adverse reactions.

  • The manifestations of digoxin toxicity include:
    • Cardiac arrhythmias, such as ventricular tachycardia or ventricular fibrillation
    • Progressive bradyarrhythmias
    • Heart block
    • Gastrointestinal disturbances, such as nausea, vomiting, and diarrhea
    • CNS disturbances, such as confusion, delirium, and hallucination
  • The risk of digoxin toxicity is increased in patients with certain conditions, such as electrolyte disturbances or concurrent medications.
  • Treatment of digoxin toxicity may involve withdrawal of the drug, correction of electrolyte disorders, and administration of a specific antidote, such as DIGIBIND 2.

From the Research

Definition and Causes of Digoxin Toxicity

  • Digoxin toxicity can occur during long-term therapy or after an overdose, even when the serum digoxin concentration is within the therapeutic range 3.
  • The narrow therapeutic index of digoxin makes it prone to toxicity, which can be triggered by various factors such as aging, comorbid diseases, and polypharmacy 4.
  • Digoxin toxicity can cause a range of symptoms, including anorexia, nausea, vomiting, neurological symptoms, and fatal arrhythmias 3, 4.

Diagnosis and Management of Digoxin Toxicity

  • The diagnosis of digoxin toxicity can be challenging due to its nonspecific signs and symptoms, and a high index of suspicion is crucial for early recognition and appropriate management 4.
  • Digoxin-specific antibody fragments (digoxin-Fab) are safe and effective in treating severe digoxin toxicity, and their use is recommended in patients with life-threatening arrhythmias and elevated digoxin concentrations 5, 3.
  • The dose of digoxin-Fab required depends on the amount ingested and serum digoxin concentration, but these are not essential for determining the dose 3.
  • Monitoring should continue after treatment with digoxin-Fab due to the small risk of rebound toxicity 3.

Treatment Approaches

  • Digoxin-Fab has a mean plasma half-life of 19-30 hours and a volume of distribution of 0.4 L/kg, and its half-life is prolonged in renal failure 5.
  • The recommended dose of digoxin-Fab in acute poisoning is 80 mg, repeated as required according to clinical parameters, while in chronic poisoning, 40 mg (1 vial) is suggested, repeated after 60 minutes if the patient is still symptomatic 5.
  • Expert consensus recommends considering the time of ingestion and nature of the exposure (acute, acute-on-chronic, chronic) and using digoxin immune Fab for life-threatening exposure to decrease the risk of death 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Management of digoxin toxicity.

Australian prescriber, 2016

Research

Digoxin: current use and approach to toxicity.

The American journal of the medical sciences, 2008

Research

Digoxin-specific antibody fragments in the treatment of digoxin toxicity.

Clinical toxicology (Philadelphia, Pa.), 2014

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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