Early Treatment for Digoxin overdose

Digoxin is the most commonly prescribed cardioactive corticosteroid in the US. It is indicated for the treatment of mild to moderate heart failure.1 In therapeutic doses, digoxin increases cardiac contractility and controls the heart rate.

Digoxin toxicity is a clinical diagnosis that relies in part on ECG findings such as signs of increased automaticity and atrioventricular node blockade (premature ventricular contractions, slowed ventricular response).

Serum digoxin concentration is usually greater than the therapeutic range of 0.5 to 0.9 nanograms/mL, but may not be elevated.

In addition to pharmaceuticals, toxicity can also occur from exposure to a number of plants and animals that contain cardioactive corticosteroids, including dogbane, foxglove, lily of the valley, oleander, yellow oleander, red quill, and the Bufo species toad.

Although these other toxins are clinically similar, this topic specifically discusses toxicity from digoxin.


General toxicity from digoxin is typically classified as acute or chronic.


Digoxin usage is decreasing due to its inferiority to other heart failure medications and digoxin toxicity has, therefore, become less common; but it is at risk of being overlooked.2

Using 2005-2010 reports from the National Electronic Injury Surveillance System, an estimated 5156 emergency department visits for digoxin toxicity occurred annually in the US, of which >75% resulted in hospital admissions.3

Digoxin toxicity accounted for approximately 1.0% of all emergency department visits for all adverse drug events among patients aged ≥40 years; this figure was estimated to be 3.3% for patients aged ≥85 years.3

Drug-drug interactions involving digoxin are a common cause of adverse drug effects in older people.4

Rate of emergency department visits and hospitalization for digoxin toxicity appear to be greater for women than men.3,5

Young children are mainly at risk of unintentional medication overdose; adults are mainly at risk from intentional ingestions in a suicide attempt. Dosing errors, increased bioavailability, and decreased clearance may also result in overdose.


Digoxin toxicity can occur through a number of different mechanisms:


  • Overdose after suicide attempt
  • Medication dosing error
  • Malicious intent (homicidal poisoning).


  • Chronic digoxin overmedication
  • Increased gastrointestinal absorption (caused by antibacterial therapy, or by drug-induced P-glycoprotein inhibition)6,7
  • Decreased renal clearance due to renal insufficiency or drugs8,9
  • Displacement of digoxin from protein binding sites8,9
  • Conditions that increase susceptibility to digoxin (electrolyte abnormalities, e.g., hypokalemia, hypomagnesemia, hypercalcemia)10,11
  • Digoxin is largely dependent on p-glycoprotein for elimination. Thus, medications that inhibit p-glycoprotein may increase digoxin levels and potentially cause toxicity. These are numerous, but clinically significant ones include verapamil, diltiazem, amiodarone, quinidine, ketoconazole, itraconazole, vinblastine, doxorubicin, 2,4-dinitrophenol, and erythromycin. These substances may also inhibit cytochrome 3A4.[18] Others include clarithromycin, cyclosporine, propafenone, quinidine, and spironolactone.

Diagnostic Approach

History and physical examination can provide clues towards the diagnosis of digoxin overdose. ECG, digoxin level, electrolytes, and renal function tests should be ordered in all patients who present with suspected digoxin toxicity or exposure.

Digoxin toxicity should be suspected in patients with a history of heart failure or atrial fibrillation, particularly in patients with renal insufficiency.

A drug history should be taken, including any supplements, herbal remedies, over the counter medications and any plant ingestions, with particular attention to the use of p-glycoprotein/cytochrome 3A4 inhibitors.

History and exam in acute toxicity

In acute digoxin toxicity, patients or family members may provide the history of exposure or suicidality. Acute digoxin toxicity is characterized by patients being asymptomatic for minutes to hours after an exposure to digoxin, followed by a rapid deterioration.

The symptoms usually include nausea, vomiting, anorexia, diarrhea, and/or abdominal pain (less common), and may include palpitations, syncope and dyspnea. Acute digoxin toxicity may cause virtually any dysrhythmia. The 2 medications used most commonly in clinical practice are digoxin and digitoxin.

History and exam in chronic toxicity

Chronic digoxin toxicity is more common in elderly patients. It has a more indolent course with a less obvious presentation

It should be considered if the following symptoms are present: nausea, anorexia, abdominal pain, weakness, fatigue, palpitations, syncope, dyspnea, disturbances of color vision with a tendency to yellow halos (xanthopsia), blurred vision, and diplopia.

Patients most often present with gastrointestinal signs (anorexia and vomiting) and generalized nonspecific complaints (generalized weakness and malaise), but could also present with central nervous system depression.

Risk Factors

  • Age >55 years
  • Decreased renal clearance
  • Hyperkalemia (>5.0 meq/l)
  • Hypokalemia (<3.0 to 3.5 meq/l)
  • Concomitant use of specific drugs
  • Hypomagnesemia
  • Hypercalcemia
  • Hypothyroidism

See also: Acute sinusitis Overview

Treatment Approach

The main goal of treatment is to correct cardiac toxicity. Treatment of cardiac toxicity usually leads to resolution of central nervous system and gastrointestinal (GI) symptoms.

Initial treatment includes:

  • General supportive care
  • Discontinuation of digoxin therapy and prevention of further exposure
  • Prevention of further GI absorption
  • Administration of digoxin-specific antibody fragments (digoxin immune Fab)
  • Treatment of specific complications: for example, dysrhythmias and electrolyte abnormalities.

Treatment of chronic toxicity is based on a clinical syndrome, not the serum digoxin concentration, which might be just above the therapeutic range.

If a serum digoxin concentration cannot be obtained, patients are managed based on their presentation, ECG findings, and laboratory results. If toxicity is suspected and the patient is unstable, antidotal therapy is administered prior to confirmatory results.

For patients with chronic digitalis poisoning, therapy may require only a few Fab vials. There is no change in therapy for renal failure other than to note that the elimination half-life of digoxin is prolonged in patients with renal failure.

Supportive care

General supportive care includes attaching patients to a cardiac monitor, providing intravenous fluids in patients with hypotension or volume depletion (with caution for patients with congestive heart failure), supplemental oxygen, and/or repletion of electrolytes in patients with electrolyte abnormalities.

Digoxin binding therapy

Digoxin binding (with digoxin immune Fab) is used in patients with the following features:

  • Severe toxicity or hemodynamic compromise
  • Symptomatic bradyarrhythmias
  • Ventricular dysrhythmias
  • Any patient with digoxin overdose and potassium concentrations >5.0 mEq/L
  • Acute ingestion of >4 mg in a healthy child (or 0.1 mg/kg)
  • Acute ingestion of >10 mg in a healthy adult
  • Serum concentration of ≥10 nanograms/mL 4-6 hours after ingestion (steady state)
  • Serum concentration of ≥15 nanograms/mL at any time.

If indicated, 15 vials of Fab is the quantity typically needed to treat one patient.12 One study suggests 1-2 vials administered in a stepwise fashion based on clinical response.13

Patients who receive digoxin immune Fab have a drop in the serum potassium as it moves intracellularly.14,15

Some patients who have been treated for hyperkalemia and who have also received digoxin immune Fab develop profound hypokalemia.

Therefore, serial potassium measurements are made when patients receive both digoxin immune Fab and other therapies to decrease potassium.16

After administration of digoxin immune Fab, serum digoxin concentrations are usually falsely elevated (10- to 30-fold). Serum digoxin concentration can be measured again 3-4 days after the dose is given,17,18but has been reported to be elevated for up to 10 days, especially in patients with renal insufficiency.18

In certain patients with chronic digoxin toxicity, supportive case is suggested to have similar outcomes to digoxin Fab.19

Management of electrolyte abnormalities

In patients with chronic digoxin toxicity, hyperkalemia is only corrected (e.g., with insulin/glucose) if it is considered life-threatening, because of the risk of producing hypokalemia.

One study showed that insulin interacts directly with Na+/K+ ATPase pumps and alters the effect of digoxin.20 This supports the finding that for patients with diabetes, insulin does not have cardioprotective effects after digoxin intoxication.

Calcium is not used to treat hyperkalemia in patients with suspected digoxin toxicity as it may induce arrhythmia or cardiac arrest.

Patients with acute digoxin toxicity and serum potassium concentrations ≥5.0 mEq/L are treated with digoxin immune Fab; those with hyperkalemia have high mortality rates.

Also, patients with hypokalemia or hypomagnesemia require additional potassium or magnesium with careful monitoring to restore normal serum levels.

GI decontamination

There is a role for GI decontamination with activated charcoal in patients with an acute ingestion of digoxin with low to moderate toxicity.21,22 The primary goal of activated charcoal is to decrease GI absorption of the drug.22,23

Bradycardia management

Adult patients with symptomatic bradycardia are treated with atropine.16 Atropine can be given every 3-5 minutes until there is a response or the 3-mg maximum dose is reached. Pediatric patients with symptomatic bradycardia require lower doses of atropine.

Tachyarrhythmia management

Type IB anti-arrhythmics (e.g., phenytoin, lidocaine) can be used if digoxin immune Fab is unavailable or is being prepared and patients have rapid ventricular dysrhythmias unresponsive to supportive measures.

Transthoracic electrical cardioversion for atrial tachyarrhythmias is associated with the development of lethal ventricular dysrhythmias, so is not used.24

Overdrive suppression with a transvenous pacemaker is also avoided because of associated iatrogenic complications that have been seen in as many as 36% of patients.25,26

Patients with ventricular fibrillation or pulseless ventricular tachycardia require defibrillation along with immunotherapy.

Hemodynamic compromise management

In patients with signs of hemodynamic insufficiency and/or compromise (e.g., hypotension, altered consciousness), digoxin immune Fab is given as primary management.

As a bridge to the administration of digoxin immune Fab, intravenous fluids and direct-acting vasopressors (e.g., phenylephrine, norepinephrine) are used. Cardiac contractility (inotropy) is typically preserved in patients with digoxin toxicity.

Ongoing monitoring and change of medication

Ideally, digoxin is discontinued and a different medication for rate control or a different inotrope prescribed (for atrial fibrillation, atrial flutter or CHF, respectively).

If the patient has to remain on digoxin for some reason, then the dose of digoxin is adjusted for the patient’s medication profile. Glomerular filtration rate and serum digoxin concentration is monitored regularly (every 2-4 weeks).


Primary Prevention

Patients on digoxin require periodic monitoring of their renal function and adjustment of their digoxin dose if creatinine clearance has changed. Serum digoxin concentration is measured 2-3 weeks after any change in therapy or addition of a new medication.

Serum digoxin concentrations are unreliable if obtained earlier than 6 hours after a dose of digoxin.27 The current therapeutic serum digoxin concentration is 0.5 to 0.9 nanograms/mL in patients with heart failure.28

Secondary Prevention

Alternative treatments are effective for two of the major clinical indications for digoxin, congestive heart failure and atrial fibrillation, and may be considered in place of digoxin, particularly in a patient who has experienced toxicity.27,28


  1. Withering W. An account of the foxglove, and some of its medical uses: with practical remarks on dropsy and other diseases. Birmingham: Swinney for Robinson; 1785.
  2. Yang EH, Shah S, Criley JM. Digitalis toxicity: a fading but crucial complication to recognize. Am J Med. 2012 Apr;125(4):337-43.
  3. See I, Shehab N, Kegler SR, et al. Emergency department visits and hospitalizations for digoxin toxicity: United States, 2005 to 2010. Circ Heart Fail. 2014 Jan;7(1):28-34.
  4. Obreli-Neto PR, Nobili A, de Oliveira Baldoni A, et al. Adverse drug reactions caused by drug-drug interactions in elderly outpatients: a prospective cohort study. Eur J Clin Pharmacol. 2012 Dec;68(12):1667-76.
  5. Aarnoudse AL, Dieleman JP, Stricker BH. Age- and gender-specific incidence of hospitalisation for digoxin intoxication. Drug Saf. 2007;30(5):431-6.
  6. Bizjak ED, Mauro VF. Digoxin-macrolide drug interaction. Ann Pharmacother. 1997 Sep;31(9):1077-9.
  7. De Lannoy IA, Koren G, Klein J, et al. Cyclosporin and quinidine inhibition of renal digoxin excretion: evidence for luminal secretion of digoxin. Am J Physiol. 1992 Oct;263(4 Pt 2):F613-22.
  8. Fenster PE, White NW Jr, Hanson CD. Pharmacokinetic evaluation of the digoxin-amiodarone interaction. J Am Coll Cardiol. 1985 Jan;5(1):108-12.
  9. Moysey JO, Jaggarao NS, Grundy EN, et al. Amiodarone increases plasma digoxin concentrations. Br Med J 1981 Jan 24;282(6260):272.
  10. Colt HG, Shapiro AP: Drug-induced illness as a cause for admission to a community hospital. J Am Geriatr Soc. 1989 Apr;37(4):323-6.
  11. Steiness E. Digoxin toxicity compared with myocardial digoxin and potassium concentration. Br J Pharmacol. 1978 Jun;63(2):233-7.
  12. Dart RC, Goldfrank LR, Erstad BL, et al. Expert Consensus guidelines for stocking of antidotes in hospitals that provide emergency care. Ann Emerg Med. 2018 Mar;71(3):314-25.e1.
  13. Chan BS, Buckley NA. Digoxin-specific antibody fragments in the treatment of digoxin toxicity. Clin Toxicol (Phila). 2014 Sep-Oct;52(8):824-36.
  14. Antman EM, Wenger TL, Butler VP Jr, et al. Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments: final report of a multicenter study. Circulation. 1990;81:1744-1752.
  15. Smith TW, Haber E, Yeatman L, et al. Reversal of advanced digoxin intoxication with Fab fragments of digoxin-specific antibodies. N Engl J Med. 1976 Apr 8;294(15):797-800.
  16. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS Guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol.2019 Aug 20;74(7):e51-156.
  17. Lemon M, Andrews DJ, Binks AM, et al. Concentrations of free serum digoxin after treatment with antibody fragments. Br Med J (Clin Res Ed). 1987 Dec 12;295(6612):1520-1.
  18. Miller JJ, Straub RW Jr, Valdes R Jr. Analytical performance of a monoclonal digoxin assay with increased specificity on the ACS:180. Ther Drug Monit. 1996 Feb;18(1):65-72.
  19. Chan BS, Isbister GK, Page CB, et al. Clinical outcomes from early use of digoxin-specific antibodies versus observation in chronic digoxin poisoning (ATOM-4). Clin Toxicol (Phila). 2018 Dec 26:1-6.
  20. Oubaassine R, Weckering M, Kessler L, et al. Insulin interacts directly with Na(+)/K(+)ATPase and protects from digoxin toxicity. Toxicology. 2012 Sep 4;299(1):1-9.
  21. de Silva HA, Fonseka MM, Pathmeswaran A, et al. Multiple-dose activated charcoal for treatment of yellow oleander poisoning: a single-blind, randomised, placebo-controlled trial. Lancet. 2003 Jun 7;361(9373):1935-8.
  22. Boldy DA, Smart V, Vale JA. Multiple doses of charcoal in digoxin poisoning. Lancet. 1985 Nov 9;2(8463):1076-7.
  23. Ibanez C, Carcas AJ, Frias J, et al. Activated charcoal increases digoxin elimination in patients. Int J Cardiol. 1995 Jan 27;48(1):27-30.
  24. Sarubbi B, Ducceschi V, D’Andrea A, et al. Atrial fibrillation: what are the effects of drug therapy on the effectiveness and complications of electrical cardioversion? Can J Cardiol. 1998 Oct;14(10):1267-73.
  25. Bismuth C, Gaultier M, Conso F, et al. Hyperkalemia in acute digitalis poisoning: prognostic significance and therapeutic implications. Clin Toxicol. 1973;6(2):153-62.
  26. Taboulet P, Baud FJ, Bismuth C, et al. Acute digitalis intoxication–is pacing still appropriate? J Toxicol Clin Toxicol. 1993;31(2):261-73.
  27. Gheorghiade M, van Veldhuisen DJ, Colucci WS. Contemporary use of digoxin in the management of cardiovascular disorders. Circulation. 2006 May 30;113(21):2556-64.
  28. Rathore SS, Curtis JP, Wang Y, et al. Association of serum digoxin concentration and outcomes in patients with heart failure. JAMA. 2003 Feb 19;289(7):871-8.

Leave a Comment