Important Safety Information Full Prescribing Information
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Potentially Fatal Digoxin Toxicity

Digoxin Toxicity Remains an Important Clinical Problem

As the Aging Population Grows, Digoxin Continues to Play a Role in the Management of Atrial Fibrillation and Heart Failure1

Incidence of Atrial Fibrillation Has Steadily Climbed in Both Inpatient and Outpatient Settings2,*
atrial fibrillation incidence chart

Results from a retrospective cohort study of 514,293 patients from 2001–2018 who received primary care and other healthcare services through a single integrated healthcare delivery network.2

What Causes Digoxin Toxicity?

Digoxin toxicity is a life-threatening condition that typically occurs when the serum digoxin concentration rises above the therapeutic range leading to adverse effects.3

Digoxin toxicity may arise due to acute or chronic intoxication4

Chronic Digoxin Toxicity5,6

  • Kidney injury may reduce elimination of digoxin
  • Drug-drug interactions may enhance the effects of digoxin or lead to increased digoxin concentrations
  • Electrolyte imbalance may increase sensitivity to digoxin (eg, hypokalemia, hypercalcemia, hypomagnesemia)

Acute Digoxin Toxicity4

  • Unintentional overdose (accidental ingestion)
  • Intentional overdose/suicide attempt

Digoxin Toxicity (or Digoxin Poisoning) May Result in Serious Clinical Outcomes, Including Death3,6,7

  • Digoxin toxicity represents 3.3% of ED visits and 5.9% of hospitalizations due to adverse drug events in patients aged ≥85 years8
  • Annual deaths due to digoxin are 4x higher than for lithium and warfarin combined1

ED, emergency department.

skull and crossbones

Potentially toxic levels of digoxin

Serum digoxin concentration of >0.9 ng/mL has been associated with increased mortality3

References

  1. Gona SR, Rosenberg J, Fyffe-Freil RC, Kozakiewicz JM, Money ME. Review: Failure of current digoxin monitoring for toxicity: new monitoring recommendations to maintain therapeutic levels for efficacy. Front Cardiovasc Med. 2023;10:1179892. 
  2. Williams BA, Chamberlain AM, Blankenship JC, Hylek EM, Voyce S. Trends in atrial fibrillation incidence rates within an integrated healthcare delivery system, 2006 to 2018. Jama Netw Open. 2020;3(8):e2014874.
  3. Goldberger AL, Traub SJ. Cardiac arrhythmias due to digoxin toxicity. UpToDate. Updated June 2020. Accessed November 21, 2023. https://www.uptodate.com/contents/cardiac-arrhythmias-due-to-digoxin-toxicity 
  4. Kanji S, MacLean RD. Cardiac glycoside toxicity more than 200 years and counting. Crit Care Clin. 2012(4);28:527-535. 
  5. Digoxin oral solution. Package insert. Roxane Laboratories, Inc.; 2011.
  6. Levine MD, O’Connor A. Digitalis (cardiac glycoside) poisoning. UpToDate. Updated April 2020. Accessed November 21, 2023. https://www.uptodate.com/contents/digitalis-cardiac-glycoside-poisoning
  7. Angraal S, Nuti SV Masoudi FA. Digoxin use and associated adverse events among older adults. Am J Med. 2019;132(10):1191-1198.
  8. See I, Shehab N, Kegler SR, Laskar R, Budnitz DS. Emergency department visits and hospitalizations from digoxin toxicity: United States, 2005 to 2010. Circ Heart Fail. 2014;7(1):28-34. 
  9. 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;71(3):314-325.

INDICATIONS AND USAGE

DIGIFab is indicated for the treatment of patients with life-threatening or potentially life-threatening digoxin toxicity or overdose, including:

  • Known suicidal or accidental consumption of fatal doses of digoxin: 10 mg or more of digoxin in healthy adults, or 4 mg (or more than 0.1 mg/kg) in healthy children, or ingestion of an amount that can cause steady state serum concentrations of ≥10 ng/mL;
  • Chronic ingestions causing steady-state serum digoxin concentrations >6 ng/mL in adults or 4 ng/mL in children;
  • Manifestations of life-threatening toxicity of digoxin overdose such as severe ventricular arrhythmias, progressive bradycardia, and second or third degree heart block not responsive to atropine, serum potassium levels exceeding 5.5 mEq/L in adults or 6 mEq/L in children with rapidly progressive signs and symptoms of digoxin toxicity.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

General

Suicidal ingestion may result from more than one drug. Consider toxic effects of other drugs or poisons in cases where signs and symptoms of digitalis toxicity are not relieved by administration of DIGIFab.

Rapid drop in serum potassium concentration may occur after treatment. Monitor frequently.

Patients with poor cardiac function may deteriorate secondary to the withdrawal of the inotropic action of digoxin by DIGIFab. Monitor frequently and provide additional inotropic support if needed. Postpone re-digitalization, if possible, until the Fab fragments have been eliminated; this may require several days or a week or longer in patients with impaired renal function.

Hypersensitivity Reactions

Anaphylaxis and hypersensitivity reactions are possible. Carefully monitor patients for signs and symptoms of an acute allergic reaction and if one occurs, stop the infusion and treat immediately with appropriate emergency medical care.

Patients with known allergies to sheep protein or those who have previously received intact ovine antibodies or Fab are particularly at risk for an anaphylactic reaction.

Do not administer DIGIFab to patients with a known history of hypersensitivity to papaya or papain unless the benefits outweigh the risks and appropriate management for anaphylactic reactions is readily available.

Use of DIGIFab in Renal Failure

The elimination half-life of DIGIFab in renal failure has not been clearly defined. Monitor patients with severe renal failure who receive DIGIFab for a prolonged period for possible recurrence of toxicity. Monitoring of free (unbound) digoxin concentrations after the administration may be appropriate.

Laboratory Tests

DIGIFab may interfere with digitalis immunoassay measurements. Thus, standard serum digoxin concentration measurements may be clinically misleading until the Fab fragments are eliminated from the body. This may take several days or a week or more in patients with markedly impaired renal function. If possible, obtain serum digoxin samples before DIGIFab administration to establish the level of serum digoxin at the time of diagnosis.

The total serum digoxin concentration may rise precipitously following administration of DIGIFab, but this will be almost entirely bound to the Fab fragment and not able to react with receptors in the body.

Adverse Reactions

The most common adverse reactions (>7%) related to DIGIFab administration are worsening congestive heart failure (13%), hypokalemia (13%) and worsening atrial fibrillation (7%).

Please see full Prescribing Information.