Important Safety Information Full Prescribing Information
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Risk Factors for Digoxin Toxicity

Risk Factors for Digoxin Toxicity Should Raise the Index of Clinical Suspicion

  • Patients undergoing digoxin therapy who exhibit risk factors for digoxin toxicity should be closely monitored so that any signs of poisoning are identified early to ensure timely treatment.1

Risk factors for potentially life-threatening digoxin toxicity

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Decreased Renal Function1,4

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Renal impairment can lead to increased digoxin levels, as digoxin is primarily eliminated by the kidneys1-4

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Multiple Concomitant Medications4

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Many medications can cause pharmacokinetic and pharmacodynamic interactions with digoxin or a decrease in renal function4

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Advanced Age and Medical Illness3-6

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Older patients are more likely to have decreased renal function and to be taking potentially interacting concomitant medications3-5; advanced heart failure is also associated with decreased renal function6

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Electrolyte Imbalance1,2

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Certain electrolyte imbalances (e.g., hypokalemia, hypercalcemia, hypomagnesemia) can increase sensitivity to digoxin effects1,2*

Particularly with loop diuretic use in chronic digoxin toxicity, hypokalemia may increase sensitivity to digoxin effects2

*In patients with toxicity from acute ingestion, hyperkalemia is associated with high mortality2

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Fluid Status1,4

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Fluid loss or poor fluid intake can lead to electrolyte imbalance1,4

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Any ONE
should raise clinical suspicion for
POTENTIALLY LIFE-THREATENING DIGOXIN TOXICITY


Many Commonly Prescribed Drugs Have Interactions With Digoxin

Common medications that interact with digoxin2†
Antiarrhythmics Amiodarone, propafenone, quinidine Calcium channel blockers Nifedipine, diltiazem, verapamil
Antibiotics Macrolides, tetracyclines Diuretics Spironolactone
Antiviral Ritonavir Immunosuppressants Cyclosporine
Antidiarrheal agents Diphenoxylate NSAIDs Diclofenac, indomethacin
Antifungals Azole antifungals Benzodiazepines Alprazolam
Antimuscarinic agent Propantheline Beta blockers Carvedilol
ACEI/ARBs Captopril, telmisartan PPI Lansoprazole, omeprazole, esomeprazole, rabeprazole
Antidiabetic agents Metformin
Antiarrhythmics Amiodarone, propafenone, quinidine
Antibiotics Macrolides, tetracyclines
Antiviral Ritonavir
Antidiarrheal agents Diphenoxylate
Antifungals Azole antifungals
Antimuscarinic agent Propantheline
ACEI/ARBs Captopril, telmisartan
Antidiabetic agents Metformin
Calcium channel blockers Nifedipine, diltiazem, verapamil
Diuretics Spironolactone
Immunosuppressants Cyclosporine
NSAIDs Diclofenac, indomethacin
Benzodiazepines Alprazolam
Beta blockers Carvedilol
PPI Lansoprazole, omeprazole, esomeprazole, rabeprazole

58% of digoxin toxicity cases had the patient start a new medication prior to their ED admission7,‡

†Not an exhaustive list of drug interactions with digoxin.
‡Results from a retrospective chart review from 2019 to 2022 on all patients admitted with a toxic serum digoxin level where the established therapeutic range for digoxin was 0.8-2.0 ng/ml.7
ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; ED, emergency department; NSAID, nonsteroidal anti-inflammatory drug; PPI, proton pump inhibitor.

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For potentially life-threatening digoxin toxicity, think R.A.P.I.D.1-3

Recognize. Act. Promptly Infuse DIGIFab

View Efficacy Data
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Digoxin Toxicity Clinical Assessment Tool

Understand how to assess for potentially life-threatening digoxin toxicity and learn when to intervene with DIGIFab.

Access the Free Clinical Tool

References

  1. 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
  2. Digoxin oral solution [package insert]. Roxane Laboratories, Inc.; 2011.
  3. DIGIFab Digoxin Immune Fab (ovine) [package insert]. BTG International Inc.; 2017.
  4. Wofford JL, Ettinger WH. Risk factors and manifestations of digoxin toxicity in the elderly. Am J Emerg Med. 1991;9(2):11-15.
  5. 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
  6. McAlister FA, Ezekowitz A, Tonelli M, Armstrong PW. Renal insufficiency and heart failure: Prognostic and therapeutic implications from a prospective cohort study. Circulation. 2004;109(8):1004-1009.
  7. 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.

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.