Bedside Snapshot
- Use It For
- Life-threatening digoxin toxicity: ventricular arrhythmias, progressive bradycardia or 2nd/3rd-degree AV block not responsive to atropine; K⁺ >5.5 mEq/L with progressing toxicity; digitoxin poisoning
- Adult Dose
- No arrest: 1–2 vials IV, titrated (differs from label)
- Acute ingestion, amount unknown and critically ill, or arrest: 10 vials IV, then 10 more
- Chronic, level unknown: 6 vials IV; level known: level × kg ÷ 100 vials
- Pediatric Dose
- Label formulas, not the adult titrated dose. Acute, amount unknown: 10–20 vials (watch volume under 20 kg). Chronic, level unknown: 1 vial under 20 kg, 6 vials at 20 kg or more
- Onset / Duration
- IV: first response in 20–60 min; arrhythmias usually resolve in 30–45 min; binding lasts days (longer in renal failure)
- Do Not Give / Hold If
- No absolute contraindication. Caution: sheep protein, papain or papaya allergy, or prior ovine Fab. Stop the infusion for hypotension, wheeze or urticaria; restart slower
- Watch For
- Rapid fall in K⁺ (13%); worsening heart failure (13%) or faster AF (7%) as digoxin effect is lost; infusion reactions; recurrent toxicity in renal failure
- Reversal / Rescue
- Inadequate response: question the diagnosis, look for co-ingestants, redose if toxicity persists or recurs. Bridge: lidocaine or phenytoin for ventricular arrhythmias; atropine or pacing for bradycardia (variable effect)
- Must Remember
- Draw the digoxin level first, but never delay Fab for it in an unstable or peri-arrest patient. Afterward total levels rise and mislead for days: treat the rhythm, perfusion and K⁺, not the number
Indications
ED / ICU / Transport
- Life-threatening digoxin toxicity: severe ventricular arrhythmias (including bidirectional VT), progressive bradycardia, or second- or third-degree AV block not responsive to atropine (AHA 2025 Class 1, B-NR)
- Hyperkalemia from digoxin poisoning: K⁺ >5.5 mEq/L in adults or >6 mEq/L in children with rapidly progressive signs of toxicity (a 2023 European consensus calls K⁺ above 6.5 mmol/L severe)
- Hemodynamic instability: hypotension or shock with end-organ dysfunction and an elevated digoxin level (toxicology consensus criterion, not a label criterion)
- Potentially fatal acute ingestion: 10 mg or more in a healthy adult; 4 mg or more (or more than 0.1 mg/kg) in a healthy child; or an expected steady-state level of 10 ng/mL or more
- Chronic toxicity with a high steady-state level: digoxin >6 ng/mL in adults or >4 ng/mL in children
- Cardiac arrest from digoxin or digitoxin poisoning: Fab goes in alongside standard ACLS/PALS. Among the arrest patients in the 150-patient multicenter series cited by AHA 2025 Part 10, 30 of 56 (54%) survived.
- Digitoxin poisoning: AHA 2025 Class 1, same as digoxin (own dose formula)
Other Uses
- Yellow oleander or Bufo toad venom poisoning: AHA 2025 Class 2a, C-LD (off-label)
- Other plant or animal cardiac glycosides (e.g. foxglove, common oleander): may be reasonable (AHA 2025 Class 2b, C-EO). The evidence is adult case reports only, and the use is off-label.
Dosing & Administration
Doses vary by protocol; follow local protocols and medical direction.
Available Forms
- DigiFab lyophilized powder: 40 mg digoxin immune Fab per single-dose vial. The vial has no preservative, and it also holds about 75 mg mannitol and 2 mg sodium acetate. Add 4 mL sterile water and it comes to about 10 mg/mL.
- Binding capacity: 1 vial (40 mg) binds about 0.5 mg of digoxin.
- Stock: it lives in the hospital pharmacy, refrigerated. EMS does not usually carry it.
Adult Dosing
| Indication | Dose & Route | Repeat / Max | Notes |
|---|---|---|---|
| Life-threatening toxicity without arrest (titrated) | 1–2 vials IV (titrated) | Repeat to bedside response until toxicity resolves; no fixed max | Differs from FDA label: the label calculates the full neutralizing dose from the amount ingested or the serum level. Reassess heart rate, rhythm and K⁺ after each dose. ATOM-6: median total 4 vials (25–35% of the calculated dose); Andrews 2023 uses the same start outside arrest and half neutralization for non-life-threatening cases. |
| Acute ingestion, amount unknown, critically ill | 10 vials IV, then repeat 10 (as the arrest row) | Label total: 20 vials; no fixed max | Use when no level or ingested amount is available; schedule as the arrest row. The label gives the 10 + 10 split to avoid a febrile reaction. |
| Cardiac arrest or arrest imminent | 10 vials IV push now, repeat 10 if no response (total 10–20) | Label: 20 vials as 10 then 10; no fixed max | AHA 2025: the ideal empiric arrest dose is unknown. A 2023 European consensus uses 5 vials, repeated once after 30 min. Bolus raises the rate of infusion reactions; accept that risk in arrest. |
| Acute ingestion, known amount | Vials = body load (mg) ÷ 0.5 IV. Tablets: body load = mg ingested × 0.8 | Round up to the next whole vial; redose if toxicity persists or recurs | Example: 25 tablets of 0.25 mg = 6.25 mg × 0.8 = 5 mg ÷ 0.5 = 10 vials. Capsules and digitoxin: no 0.8 correction. |
| Chronic toxicity, level known | Vials = digoxin level (ng/mL) × weight (kg) ÷ 100 IV | Round up to the next whole vial; redose if toxicity persists or recurs | Example: 4 ng/mL × 70 kg ÷ 100 = 2.8, round up to 3 vials. Use a steady-state level (6–8 hr or more after the last dose). |
| Chronic toxicity, level unknown | 6 vials IV | Redose by clinical response; no fixed max | Label empiric dose for adults and children 20 kg or more. |
| Digitoxin poisoning | Vials = digitoxin level (ng/mL) × weight (kg) ÷ 1,000 IV | Round up; redose by response | Denominator differs because digitoxin has a 10-fold smaller volume of distribution. |
| Yellow oleander or Bufo toad venom | 1,200 mg (30 vials) IV | AHA 2025 initial dose (also listed for other cardioactive steroids); further dosing with a toxicologist | Off-label. Cross-reactivity with plant and toad glycosides is variable. |
Pediatric Dosing
| Indication | Dose (per kg) & Route | Max Single / Max Total | Notes |
|---|---|---|---|
| Acute ingestion, amount unknown, critically ill | Same as adults: 10 vials IV, repeat 10 (not weight-based) | Label total: 20 vials; no fixed max | Watch for volume overload in children under 20 kg. |
| Acute ingestion, known amount | Same formula as adults: vials = body load (mg) ÷ 0.5 IV | Round up; redose if toxicity persists or recurs | Potentially fatal: 4 mg or more, or more than 0.1 mg/kg. |
| Chronic toxicity, level known, 20 kg or more | Vials = level (ng/mL) × weight (kg) ÷ 100 IV | Round up; redose by response | Same as adults. |
| Chronic toxicity, level known, under 20 kg | Dose in mg = (level × weight ÷ 100) × 40 mg IV | Redose by response; no fixed max | Example: 10 kg at 4 ng/mL = 0.4 vial × 40 mg = 16 mg. |
| Chronic toxicity, level unknown | Under 20 kg: 1 vial IV; 20 kg or more: 6 vials IV | Redose by clinical response; no fixed max | Label empiric doses. |
| Yellow oleander or Bufo toad venom | Pediatric dose unknown per AHA 2025: consult | — | Off-label; dose with a toxicologist or poison center. |
| Neonates and infants | Same mg formula as under 20 kg (label table starts at 1 kg) | Redose by response | Safety data are limited; dosing is extrapolated from adults. |
AHA 2025 Part 10 gives no pediatric figure for the titrated dose. That row is adults only, and a child who may need it means a call to the poison center (below).
Weight-based dose checks: pediatric weight-based dosing.
Preparation & Administration
- Reconstitution: 4 mL sterile water for injection per vial, mixed gently (about 10 mg/mL). Do not use if cloudy or containing particles.
- Dilution: add the dose to 0.9% sodium chloride. For very small pediatric doses, dilute one reconstituted vial with 36 mL of 0.9% sodium chloride to 1 mg/mL.
- Rate: IV infusion over at least 30 min. If cardiac arrest is imminent, give as a bolus.
- Infusion reaction: stop and restart slower (see Hold / Reassess).
- Before the first vial: draw a serum digoxin level and a K⁺ if at all possible. In an unstable patient, never delay the Fab for either one.
Dosing Notes:
- Two calculations, two answers? The label points you to the higher one.
- Levels go in as ng/mL. Plug in nmol/L and you overstate the dose by about 28%. The formulas assume a digoxin volume of distribution of about 5 L/kg. Round up. Conversions and draw timing: digoxin level page.
Contraindications & Precautions
Contraindications
- None known (FDA label). In life-threatening toxicity, an allergy history means prepare for anaphylaxis. It is not a reason to withhold the antidote.
Precautions
- Sheep protein allergy or prior ovine antibody or Fab therapy (e.g. a previous DigiFab course or CroFab antivenom): anaphylaxis risk runs higher.
- Papain, chymopapain, papaya or bromelain (pineapple enzyme) allergy: Fab is made by papain digestion. Give it only when the benefit outweighs the risk, and have anaphylaxis treatment ready.
- Poor cardiac function or AF rate controlled by digoxin: Fab removes its inotropic and AV-nodal effects, and heart failure or a fast ventricular rate can follow.
- Renal failure: Fab and Fab-digoxin complexes clear slowly. Toxicity can come back. Monitor for longer.
- Suicidal ingestion: look for co-ingestants. Look hardest when toxicity does not respond to Fab.
- Children under 20 kg: a large empiric dose risks volume overload.
Hold / Reassess If
- Hypotension, wheeze or urticaria during the infusion: stop; restart more slowly once resolved. Anaphylaxis: stop and treat.
- No response after an adequate dose? See Clinical Pearls before you give more.
Epinephrine for anaphylaxis: the label says to weigh its benefit against arrhythmia risk in digitalis toxicity. In true anaphylaxis, don't withhold it. Titrate it on continuous ECG monitoring.
Adverse Effects & Toxicity
Common
- Worsening heart failure: 13% (label). It comes from losing digoxin's inotropic support.
- Hypokalemia: 13% (label). It can come on fast as K⁺ moves back into cells.
- Worsening AF (faster ventricular rate): 7% (label)
- Other (frequency not established): why split large empiric doses 10 + 10 vials? Febrile reaction is the reason. Infusion-site phlebitis and transient postural hypotension also occur.
- Postmarketing: the 1986–2019 FDA reports raised no new safety concerns and no deaths attributable to Fab.
Serious / Life-Threatening
| Effect | Recognition | Management |
|---|---|---|
| Rapid hypokalemia | Falling K⁺ in the first hours after Fab, new ectopy | Frequent K⁺ checks; cautious replacement (the patient may have a total-body K⁺ deficit despite initial hyperkalemia) |
| Decompensated heart failure or rapid AF | Hypotension, pulmonary edema, rising ventricular rate | IV inotropes (dobutamine, dopamine) or vasodilators with ECG monitoring; alternative rate control; do not restart digoxin yet |
| Anaphylaxis | Urticaria, angioedema, bronchospasm, stridor, hypotension, tachycardia | Stop the infusion; oxygen, airway, fluids, diphenhydramine, corticosteroids; epinephrine as needed (see warning) |
| Recurrent (rebound) toxicity | Arrhythmia or bradycardia returns hours later; most likely with renal failure or small titrated doses | Redose by clinical judgment; use free digoxin levels if available |
Overdose & Toxicity Management
- Fab overdose: the label describes no overdose syndrome. A large dose risks losing digoxin's therapeutic effect (heart failure, fast AF) and adding fluid volume in small children. Treat supportively.
- Bridging until Fab acts: atropine (AHA 2025 Part 9 Class 2a, B-NR, for bradycardia with hemodynamic compromise; 1 mg IV every 3–5 min, max 3 mg) and transcutaneous pacing work unpredictably in glycoside poisoning. Pacing must not delay Fab. Lidocaine or phenytoin may be reasonable for ventricular arrhythmias until Fab is given (AHA 2025 Class 2b, C-EO).
- Cardiac arrest: run standard ACLS/PALS, defibrillation included. Add Fab by bolus.
- Hyperkalemia: Fab is the definitive treatment. For calcium, see Clinical Pearls.
- Extracorporeal removal: not recommended (AHA 2025 Class 3: No Benefit, B-NR). Digoxin's large volume of distribution is why it is not well removed.
- Poison center: 1-800-222-1222 (US; poison.org) for dosing help.
Monitoring
| Parameter | When / How Often | Target / Act If |
|---|---|---|
| Clinical: continuous ECG, BP, heart rate, temperature | Before, during and after Fab | Arrhythmia or AV block usually resolves within 30–45 min. Hypotension, wheeze or urticaria: see Hold / Reassess. Fever: possible infusion reaction. No response: see Clinical Pearls. |
| Clinical: heart failure and AF rate | Hours to days after Fab | Pulmonary edema or rapid AF: inotropes or vasodilators and alternative rate control. |
| Laboratory: K⁺, Mg²⁺, Ca²⁺ | Baseline, then frequently in the first several hours | Falling K⁺: cautious replacement (see Adverse Effects; potassium lab page). Persistent hyperkalemia with ongoing toxicity: more Fab. Correct hypomagnesemia (common with diuretics in chronic toxicity). |
| Laboratory: creatinine and urine output | Baseline and as indicated | Renal impairment: monitor for recurrent toxicity for a week or more. |
| Drug levels: total digoxin | Before Fab, if at all possible (6–8 hr or more after the last dose) | Use the pre-Fab level for dosing. After Fab, total digoxin rises sharply because the assay counts bound drug; it can read high for days, a week or more in renal failure. Do not treat the number: judge response by rhythm, perfusion and K⁺. Free digoxin, where available, if recurrence is suspected. |
| Observation and discharge | During and after Fab | Advise return for rash, itching or hives (delayed allergy or serum sickness). |
Interactions & Compatibility
Clinically Significant Interactions
| Drug / Class | Effect | What To Do |
|---|---|---|
| Digoxin restart (re-digitalization) | Circulating Fab binds new digoxin | Postpone until Fab is eliminated: several days, a week or more with renal impairment; use other rate-control drugs meanwhile |
IV Compatibility
- Diluents: sterile water to reconstitute; 0.9% sodium chloride to dilute.
- Y-site: The label gives no Y-site data. Run it on its own line or lumen where you can, and verify with an institutional compatibility resource.
Special Populations
- Pediatrics: the label formulas are extrapolated from adult data, and safety data are limited. Under 20 kg, measure in mg. Use a tuberculin syringe for volumes under 1 mL. The doses are in the Pediatric Dosing table.
- Neonates: there is no separate dosing. The label's mg table starts at 1 kg.
- Pregnancy and lactation: there are no reproduction or milk data. Give Fab when it is clinically needed. Untreated toxicity endangers mother and fetus.
- Older adults: age does not change efficacy. Renal impairment is more common, though, so monitor longer.
- Renal impairment: no dose adjustment. Toxicity can recur for days, so see Monitoring.
- Hepatic impairment: no specific adjustment established.
- Obesity: the label formula uses body weight in kg and never says actual or ideal weight. Round up and redose by response. In extreme obesity, ask the poison center.
Field & Transport Considerations
- Scope: it is started in the ED or ICU under physician or toxicologist direction. RNs and critical-care transport crews may give or continue it during interfacility transfer. Scope varies by state and agency protocol.
- Prehospital: recognize toxicity. Look for bradycardia, AV block, ectopy, bidirectional VT, GI symptoms and confusion. Bring the medication containers, note the ingestion time and amount, and pre-notify so vials are ready.
- Storage: refrigerate vials at 2–8 °C (36–46 °F); do not freeze. A reconstituted vial keeps refrigerated for 4 hr.
- Transport infusion: pump-controlled, on its own line (rate: see Dosing); keep the monitor and defibrillator pads ready.
- Handoff: pre-Fab level with draw and last-dose times, ingested amount and product, vials and times, K⁺ trend, rhythm response, creatinine, any reaction.
Clinical Pearls
Classic ECG clue (exam favorite): Bidirectional VT, or atrial tachycardia with AV block, in a patient on digoxin? Call it digoxin toxicity until proven otherwise. Lidocaine and phenytoin only buy time until Fab is given.
Calcium and the stone heart: Neither AHA 2023 nor 2025 gives a formal recommendation. The 2023 narrative cites limited data suggesting calcium is neither harmful nor beneficial. Digoxin hyperkalemia gets Fab.
No response means rethink: chronic toxicity responds less. Renal failure, AV-nodal blockers or a co-ingestant often contribute. Nothing after an adequate dose? Look for those. Don't stack vial on vial.
Pharmacology
Pharmacokinetics
| Route | Onset | Peak | Duration |
|---|---|---|---|
| IV | First response median 19 min after the infusion; 75% by 60 min (1990 multicenter series, Antman et al.) | Full reversal by 4 hr in 47% and by 20 hr in 93% (label trial) | Binding persists while Fab circulates: days, a week or more in renal failure |
- Mechanism: ovine Fab binds digoxin (affinity 10⁹–10¹⁰ M⁻¹) more tightly than Na⁺/K⁺-ATPase does. Free digoxin falls to near zero within minutes. Tissue digoxin redistributes, and K⁺ re-enters cells.
- Other: Vd about 0.4 L/kg per the 2014 Chan & Buckley review (digoxin 5–10 L/kg; the label gives no Fab Vd); molecular weight about 46,000 Da; half-life 15–20 hr with normal renal function per the label (the review cites 19–30 hr), up to 10-fold longer in impairment; renal elimination; 80% complete and 10% partial response in the 150-patient series.
Names & Classification
- Generic Name
- Digoxin immune Fab (ovine)
- Brand Names
- DigiFab (BTG International); Digibind was the older ovine product (DigiFab is the product currently listed on DailyMed)
- Pharmacologic Class
- Ovine digoxin-specific antibody fragment (monovalent Fab)
- Therapeutic Class
- Antidote (digoxin, digitoxin and other cardiac glycosides)
- Controlled Substance
- Not controlled
- ISMP High-Alert
- No
- Look-Alike / Sound-Alike
- None commonly reported; order and label it as digoxin immune Fab (DigiFab) to avoid confusion with digoxin
References
- BTG International. (2017). DigiFab (ovine digoxin immune Fab) injection, powder, lyophilized, for solution [prescribing information] (label revised June 2017; DailyMed version 11, posted October 1, 2026). DailyMed, National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c05ee6a5-c98b-45f4-83fd-40781639d653
- Cao, D., Arens, A. M., Chow, S. L., Easter, S. R., et al. (2025). Part 10: Adult and pediatric special circumstances of resuscitation: 2025 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation, 152(16 Suppl 2), S578–S672. https://doi.org/10.1161/CIR.0000000000001380
- American Heart Association. (2025). 2025 AHA Guidelines for CPR and ECC, Part 9: Adult Advanced Life Support (Initial Management of Bradycardia recommendations). https://cpr.heart.org/en/resuscitation-science/cpr-and-ecc-guidelines/adult-advanced-life-support
- Lavonas, E. J., Akpunonu, P. D., Arens, A. M., Babu, K. M., et al. (2023). 2023 American Heart Association focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning: An update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation, 148(16), e149–e184. https://doi.org/10.1161/CIR.0000000000001161
- Chan, B. S., Isbister, G. K., Chiew, A., Isoardi, K., & Buckley, N. A. (2022). Clinical experience with titrating doses of digoxin antibodies in acute digoxin poisoning (ATOM-6). Clinical Toxicology, 60(4), 433–439. https://doi.org/10.1080/15563650.2021.1968422
- Andrews, P., Anseeuw, K., Kotecha, D., Lapostolle, F., & Thanacoody, R. (2023). Diagnosis and practical management of digoxin toxicity: A narrative review and consensus. European Journal of Emergency Medicine, 30(6), 395–401. https://doi.org/10.1097/MEJ.0000000000001065
- Wei, S., Niu, M. T., & Dores, G. M. (2021). Adverse events associated with use of digoxin immune Fab reported to the US Food and Drug Administration Adverse Event Reporting System, 1986–2019. Drugs - Real World Outcomes, 8(2), 253–262. https://doi.org/10.1007/s40801-021-00242-x
- Chan, B. S., & Buckley, N. A. (2014). Digoxin-specific antibody fragments in the treatment of digoxin toxicity (landmark systematic review). Clinical Toxicology, 52(8), 824–836. https://doi.org/10.3109/15563650.2014.943907
- Antman, E. M., Wenger, T. L., Butler, V. P., Jr., Haber, E., & Smith, T. W. (1990). Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments: Final report of a multicenter study (landmark trial). Circulation, 81(6), 1744–1752. https://doi.org/10.1161/01.cir.81.6.1744
- Poison Help, American Association of Poison Control Centers. Call a poison center: 1-800-222-1222 (US). poison.org (accessed October 15, 2026). https://www.poison.org/
Medical Disclaimer
- For Educational Purposes Only: This content is intended for educational reference and should not be used for clinical decision-making.
- Not a Substitute for Professional Judgment: Always consult your local protocols, institutional guidelines, and supervising physicians.
- Verify Before Acting: Users are responsible for verifying information through authoritative sources before any clinical application.
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