Digoxin immune Fab

#complete #carded

Related FACEM curriculum (2022) learning objectives:

• ME 3.8.1.6(e) Principles of management of toxicological presentations including: Indications for antidotes
• ME 3.8.2.4 Identify the appropriate antidote or antivenom.

Digoxin Immune Fab

Presentations

• Lyophilised powder: 40 mg ampoules.

Toxicological Indications

• Cardiac glycoside poisoning with imminent life threat or inpatient care required:
  • Acute digoxin overdose:
    • Cardiac arrest.
    • Life-threatening cardiac dysrhythmia.
    • Ingested dose >10 mg (adult) or >4 mg (child).
    • Serum digoxin >15 nmol/L (12 ng/mL).
    • Serum potassium >5 mmol/L.
  • Chronic digoxin poisoning:
    • Cardiac arrest or life-threatening cardiac dysrhythmia.
    • Dysrhythmias not tolerable long-term.
    • Moderate/severe gastrointestinal symptoms.
    • Symptoms with impaired renal function.
  • Other cardiac glycoside poisoning: Oleander, bufotoxin (cane toad).

Contraindications

• None.

Mechanism of Action

• Created via papain cleavage of IgG raised in sheep against digoxin.
• One ampoule (40 mg) binds 0.5 mg digoxin.
• Binds free digoxin in plasma/interstitium with greater affinity than Na⁺/K⁺-ATPase, creating a gradient for intracellular digoxin to move into the intravascular space for neutralisation.

Pharmacokinetics

• Excreted in urine with a half-life of 16–30 hours.

Administration

General

• Place patient in a monitored area with resuscitation resources.
• Cardiac monitoring mandatory until toxicity resolves.
• Reconstitute ampoule in 100 mL normal saline; infuse over 30 minutes.

Dosage

• Acute digoxin overdose:
  • Known dose: Number of ampoules = ingested dose (mg) × 0.8 × 2.
  • Unknown dose: Start with 5 ampoules if stable; 10 ampoules if unstable. Repeat 5-ampoule doses every 30 minutes until toxicity reversal.
• Chronic digoxin poisoning:
  • Number of ampoules = (serum digoxin ng/mL × body weight kg) ÷ 100.
  • Alternatively, start with 2 ampoules and observe clinical response. Repeat 2-ampoule doses every 30 minutes as needed.
• Other cardiac glycoside poisoning:
  • Start with 5 ampoules if stable; repeat every 30 minutes until toxicity reversal. Severe cases may require up to 30 ampoules.

Duration

• Single dose over 30 minutes typically sufficient.
• Effects apparent in 20 minutes, maximal by 4 hours.
• Rarely, toxicity may recur >24 hours, necessitating further doses.

Therapeutic Endpoints

• Restoration of normal cardiac rhythm and conduction.
• Resolution of gastrointestinal symptoms.

Adverse Drug Reactions

• Hypokalaemia.
• Rare allergy.
• Exacerbation of cardiac failure.
• Loss of rate control in atrial fibrillation.

Specific Considerations

• Pregnancy and paediatrics: No restrictions.

Handy Tips

• In cardiac arrest due to digoxin toxicity, administer 20 ampoules rapidly while continuing CPR.
• Post-treatment serum digoxin levels may appear high due to measurement of Fab-bound digoxin; request assays for free digoxin if available.
• Treat hyperkalaemia with Fab, not calcium (digoxin elevates intracellular myocardial calcium).
• Partial Fab doses may suffice; full body load neutralisation is not necessary.
• For non-life-threatening chronic poisoning, Fab reduces hospital stay.

Pitfalls

• Insufficient Fab availability for life-threatening cases.
• Withholding Fab in chronic toxicity due to expense; risks of prolonged admission and death outweigh antidote cost.

Controversies

• Smaller initial doses with subsequent adjustment may optimise outcomes.
• Dosing is unclear for other glycosides (e.g., oleander).