Digoxin Immune Fab (DigiFab)

• What it is: Ovine-derived digoxin-specific antibody fragments (Fab) that bind and neutralize free digoxin.
• Primary job: Reverse life-threatening digoxin toxicity (unstable brady/AV block, ventricular arrhythmias, shock, or severe hyperkalemia in acute overdose).
• Onset: Clinical improvement typically within 20–60 minutes; full response may take several hours.
• Dose thinking: Calculate by amount ingested or serum level × weight; if peri-arrest, give empiric vials rather than waiting on data.

• Generic Name: Digoxin immune Fab (ovine)
• Brand Names: DigiFab (U.S.); Digibind (historical)

Digoxin-specific antibody fragments (ovine); specific antidote for digoxin by binding free drug and forming inactive complexes eliminated renally.

Mechanism of Action:

• High-affinity Fab fragments bind free digoxin, forming Fab–digoxin complexes.
• Reduces pharmacologically active (free) digoxin, creating a gradient that draws tissue-bound digoxin into plasma for neutralization.
• Rapid reversal of Na⁺/K⁺-ATPase inhibition improves AV conduction and stabilizes ventricular arrhythmias.
• Complexes are cleared primarily by the kidneys.

Pharmacokinetics:

• Route: IV only (reconstituted lyophilized powder; infuse over ~30 minutes; may give more rapidly in arrest).
• Onset: 20–60 minutes to initial clinical improvement; full effect over several hours.
• Distribution: Mostly intravascular/extracellular; Fab fragments do not cross cell membranes.
• Elimination: Renal clearance of free Fab and Fab–digoxin complexes; t½ ~15–20 hours with normal renal function; prolonged in renal impairment.
• Assays: Standard digoxin immunoassays read total (bound + unbound) after Fab and are not decision-useful.

• Life-threatening digoxin toxicity with hemodynamic instability or significant arrhythmias (ventricular arrhythmias, high-grade AV block, severe symptomatic bradycardia).
• Acute overdose with serum K⁺ ≥5.0–5.5 mEq/L or rapidly rising potassium.
• Known large acute ingestion (especially pediatric) with concerning symptoms/ECG changes.
• Severe chronic toxicity with significant dysrhythmias or syncope, especially in renal impairment.
• When markedly elevated steady-state digoxin levels plus worrisome ECG/clinical findings are present (in consultation with toxicology).

Available Forms:

• Lyophilized powder for IV use; each vial contains 40 mg digoxin immune Fab and binds ≈0.5 mg of digoxin (approximate).
• Reconstitute with sterile water and dilute in normal saline per labeling.

Adult Dosing (consult toxicology/Poison Center):

Calculated Dosing Options:

• Based on amount ingested (acute): Vials ≈ (mg ingested × 0.8) ÷ 0.5. Example: 5 mg → (5 × 0.8)/0.5 = 8 vials.
• Based on serum level (chronic): Vials ≈ (digoxin ng/mL × weight kg) ÷ 100. Example: 4 ng/mL × 70 kg ÷ 100 = 2.8 → 3 vials.

Administration:

• Infuse over ~30 minutes when stable; in arrest/peri-arrest, administer as a slow IV push over several minutes.
• Monitor ECG, blood pressure, and potassium closely during and after administration.

Repeat Dosing: If toxicity persists/recurs (arrhythmias, hyperkalemia, shock), give additional vials guided by clinical status and toxicology.

Contraindications:

• Known severe hypersensitivity to digoxin immune Fab or ovine (sheep) proteins.

Precautions:

• Loss of therapeutic digoxin effect may worsen heart failure or rate control in AF.
• Rapid shift of potassium can lead to hypokalemia; check K⁺ frequently and replete cautiously.
• Renal impairment prolongs Fab–digoxin complex clearance; monitor longer for recurrence.
• Standard digoxin levels are not reliable after Fab; use clinical response and ECG.
• Allergy risk with ovine proteins; treat anaphylaxis per protocol if occurs.

Common:

• Infusion reactions (flushing, chills, fever), nausea/vomiting.
• Hypokalemia after reversal of digoxin effect.
• Worsening HF symptoms in digoxin-dependent patients.

Serious:

• Anaphylaxis/severe hypersensitivity.
• Severe hypokalemia leading to arrhythmias if not monitored/repleted.
• Cardiogenic shock or decompensated HF in digoxin-dependent patients.

• Renal impairment: Expect prolonged effect and delayed complex clearance; monitor longer; repeat dosing may be needed.
• Pediatrics: Dosing uses same formulas; when unknown ingestion and unstable, 5–10 vials empirically with toxicology input.
• Pregnancy/lactation: Use when maternal benefit outweighs risk in life-threatening toxicity; protein nature suggests minimal oral bioavailability to infant.
• Older adults: Higher risk of chronic toxicity and renal impairment—lower threshold to treat when significant dysrhythmias present.

Clinical Monitoring:

• Continuous ECG for resolution of digoxin-related arrhythmias (e.g., bidirectional VT, high-grade AV block).
• Frequent vitals/hemodynamics; assess perfusion and mental status.

Laboratory Monitoring:

• Serum potassium (q1–2h initially in severe cases), magnesium, calcium.
• Renal function (BUN/Cr, urine output).
• Do not use post-Fab digoxin levels to guide therapy.

• 1. BTG International. (2023). DigiFab (digoxin immune Fab) prescribing information. https://www.digifab.com/hcp
• 2. Veltri, K., & Blank, R. (2024). Digoxin toxicity. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK556025/
• 3. Hoffman, R. S., Howland, M. A., Lewin, N. A., Nelson, L. S., & Goldfrank, L. R. (Eds.). (2019). Goldfrank’s toxicologic emergencies (11th ed.). McGraw-Hill.
• 4. BMJ Best Practice. (2024). Digoxin toxicity. https://bestpractice.bmj.com/topics/en-us/1041