Why this drug is interesting

Digoxin immune Fab is close to what an antidote should be. It is an antibody fragment raised against the poison itself, it binds digoxin with high affinity, it removes it from the receptor, and the complex is renally excreted. There is no receptor competition to titrate and no half-life mismatch to manage. In a patient dying of digoxin toxicity it works, and it works within half an hour.

What makes it worth a monograph rather than a protocol line is that the dose is genuinely contested. The current UK label and the current US prescribing information — for the same product, made by the same manufacturer — give formulas that differ by a factor of two, and empiric doses that are not directly comparable at all — each label bands its empiric dosing by a scenario the other does not describe. Neither is wrong; they reflect different national judgements about how much antidote a given degree of toxicity warrants. Most calculators and textbooks reproduce the American figures.

Pharmacology

Mechanism

DigiFab is produced by immunising sheep with a digoxin-albumin conjugate, then cleaving the resulting antibody with papain to yield Fab fragments. The Fc portion is discarded, which is what makes the product tolerable: Fab fragments are small, are less immunogenic than whole antibody, distribute rapidly into the interstitial space, and are renally cleared.

Bound digoxin cannot interact with the Na⁺/K⁺-ATPase, so the free concentration falls and toxicity reverses. The label notes that in vitro binding studies show "similar binding affinities for digoxin and plant cardiac glycoside analogues" — which is why it also works in oleander and other plant glycoside poisoning.

Kinetics

Onset: Improvement in signs and symptoms "ordinarily begin[s] within 30 minutes following completion of administration"
Elimination half-life: About 15 hours in volunteers with normal renal function
Elimination: Renal, as Fab-digoxin complexes
Renal impairment: Excretion of the complexes is slowed, and digoxin may be released after some days from retained complexes
Volume of distribution assumption: Dose estimates assume a steady-state digoxin V_d of 5 L/kg — a population average that "var[ies] widely among individuals"

Indications

The UK licensed indication is the treatment of "known (or strongly suspected) life-threatening digoxin toxicity or cardiac glycoside poisoning associated with ventricular arrhythmias or bradyarrhythmias unresponsive to atropine where measures beyond withdrawal of digoxin or cardiac glycosides and correction of serum electrolyte abnormalities are considered necessary."¹

The label groups the treatment triggers as:

Cardiac arrest due to digoxin or another cardiac glycoside
Severe bradyarrhythmia or life-threatening ventricular arrhythmia
Severe hyperkalaemia — for example K⁺ above 6.5 mmol/L — resistant to adequate rehydration and conventional treatment

It notes that this applies equally to acute overdose on top of usual therapy, acute overdose in a digoxin-naive patient, and toxicity from chronic therapy.

Dosing

Cardiac arrest due to cardiac glycoside

Give as an IV bolus; further doses may be needed if there is no adequate clinical response after 30 minutes.

Weight (adult and child)	DigiFab dose
Over 40 kg	5 vials (200 mg)
20–40 kg	2 vials (80 mg)
20 kg or under	1 vial (40 mg)

Severe arrhythmia or resistant hyperkalaemia — pharmaceutical digoxin

When a digoxin concentration is available — measured 6 hours after the overdose, unless urgently needed in a patient with arrhythmia:

Number of vials = (serum digoxin concentration (ng/mL) × weight (kg)) ÷ 200
DigiFab SmPC, section 4.2 — round up to the nearest vial

When only the ingested dose is known:

Number of vials = Amount of digoxin ingested (mg) × 0.8
DigiFab SmPC, section 4.2 — round up to the nearest vial

Concentrations reported in nmol/L must be converted: [Digoxin] nmol/L × 0.781 = [Digoxin] ng/mL (ng/mL is the same as µg/L).

Non-digoxin cardiac glycosides

For severe bradyarrhythmia, life-threatening ventricular arrhythmia or resistant hyperkalaemia from a glycoside other than pharmaceutical digoxin — yellow oleander, foxglove, lily of the valley — give as an IV bolus and repeat after 15–30 minutes if the response is inadequate:

Weight (adult and child)	DigiFab dose
Over 40 kg	2 vials (80 mg)
40 kg or under	1 vial (40 mg)

Preparation and administration

Reconstitute each vial with 4 mL of Water for Injections by gentle mixing, giving 10 mg/mL
May be diluted further to any convenient volume with 0.9% sodium chloride
Infuse over 30 minutes — or give as an IV bolus in cardiac arrest
Use immediately after reconstitution; single use only
Record the name and batch number — a traceability requirement for biological products

The UK and US labels give different doses

This is worth knowing before you use a calculator, a textbook table or a guideline of uncertain provenance.

Dose calculation — UK SmPC (June 2026) compared with US prescribing information (revised June 2017)
Scenario	UK SmPC¹	US prescribing information²
From serum concentration	(ng/mL × kg) ÷ 200	(ng/mL × kg) ÷ 100
From known ingestion	mg ingested × 0.8	(mg ingested × 0.8) ÷ 0.5 — i.e. × 1.6 for tablets
Acute ingestion, unknown amount, no level	Not given as a separate scenario	20 vials (10, then a further 10)
Chronic toxicity, no level available	Not given as a separate scenario	6 vials in adults and children ≥20 kg; 1 vial under 20 kg
Cardiac arrest	5 vials over 40 kg	Not specified as an arrest-specific dose

The UK label is roughly half the American dose, and it says why you should ask

The UK SmPC opens its posology section by advising discussion with TOXBASE and the UK National Poisons Information Service on 0344 892 0111 (NPIC in Ireland: (01) 809 2566), and directing the reader to the most current TOXBASE guidance.¹ That instruction sits in the label precisely because the dosing is a national clinical judgement rather than a settled pharmacological constant.

The US prescribing information states that each 40 mg vial binds approximately 0.5 mg of digoxin, which — with the shared assumption of a 5 L/kg volume of distribution — is the arithmetic that produces the ÷100 formula. The UK figures imply roughly twice that binding per vial. The practical reading is not that one label is in error, but that UK practice titrates Fab against the clinical response rather than aiming to neutralise the whole estimated body load, and re-doses as required. The label supports this: "If, after several hours, toxicity has not adequately reversed or appears to recur, re-administration of DIGIFAB at a dose guided by clinical judgement may be required."

Follow your local guideline and TOXBASE. If your department's proforma reproduces the ÷100 formula, that is not necessarily wrong — but it should be a deliberate choice, and someone should know which label it came from.

Complications and monitoring

Monitoring

Continuous ECG monitoring during and for at least 24 hours after administration
Temperature, blood pressure and potassium during and after
Adverse reactions may occur up to 14 days after the infusion
Children under 20 kg should be monitored for volume overload

Hypersensitivity

The only contraindication is hypersensitivity to the product. Risk is higher in patients allergic to:

Sheep-derived proteins — the Fab is ovine
Papain, used to cleave the antibody; residues may be present. Papain shares allergenic structures with chymopapain and other papaya extracts, bromelain in pineapple, dust mite allergens and latex
Alpha-gal, or diagnosed alpha-gal syndrome — a mammalian carbohydrate allergy usually acquired after tick bite

Stop the infusion immediately if an anaphylactic reaction occurs. Repeat dosing may itself provoke anaphylaxis, and should only be undertaken where the benefit outweighs that risk. There is no information on re-administration for a second episode of toxicity.

Adverse reactions

All the following are reported as common in the SmPC: hypersensitivity reactions; hypokalaemia and hyperkalaemia; headache and confusion; worsening of cardiac failure, chest pain, hypotension and orthostatic hypotension; nausea, vomiting, diarrhoea, constipation and abdominal distension; influenza-like illness; renal failure; fatigue and infusion-site phlebitis.

Practical use in the ED

Treat the arrhythmia and the potassium, not the level. A digoxin concentration taken before 6 hours after an acute ingestion is a distribution artefact, not a body load — the drug is still moving into tissue. The exception is a patient with an arrhythmia now, where waiting is not an option.
Find out whether it is digoxin. Plant glycoside poisoning uses a different dose table and cannot be dosed from an assay at all.
Call NPIS early. The label asks you to, the doses differ between jurisdictions, and Fab is expensive enough that pharmacy will want the conversation documented.
Find out where the stock is before you need it. Fab is a low-turnover, refrigerated, expensive product. Many hospitals hold only a handful of vials, and 5 vials for an arrest may be the entire stock.
Warn the receiving team about the potassium and the digoxin assay. Both will otherwise be misread — a rising total digoxin level and a falling potassium in a patient who is visibly improving.

Critical appraisal

The efficacy evidence is observational and old, and no better evidence is coming. The pivotal data are multicentre case series from the 1990s in which patients with life-threatening toxicity improved. There is no randomised comparison against supportive care, and there will not be one. As with naloxone, this is a case where mechanistic and observational evidence is a legitimate warrant, and where the absence of a trial should not be read as weakness.
The dose formulas are estimates layered on estimates. A population-average volume of distribution of 5 L/kg — which the label itself says "var[ies] widely among individuals" — is used to convert a concentration into a body load, which is then converted into vials by a binding assumption. The apparent precision of a formula that rounds up to the nearest vial is not real precision.
The UK–US divergence is a genuine and under-discussed disagreement. Two current labels for one product, differing twofold in a life-saving antidote, is unusual. Most digital dose calculators reproduce the US figures without stating which jurisdiction they reflect — and a UK clinician using one will not be told.
Cost shapes practice in a way nobody quite says out loud. Fab is expensive and stocked in small quantities. That is not a clinical argument for a lower dose, but it is a real constraint that quietly favours the titrate-and-repeat approach the UK label describes, and it is more honest to name it than to pretend dosing decisions are purely pharmacological.
The clinical response is a better endpoint than any calculation, and both labels ultimately say so. Reversal of arrhythmia, resolution of hyperkalaemia and improved conduction are visible within half an hour, and re-dosing on clinical grounds is explicitly sanctioned.

References

1
DigiFab 40 mg/1 vial powder for solution for infusion — Summary of Product Characteristics, SERB (MA holder Protherics UK Ltd). electronic Medicines Compendium. Sections 4.1–4.4, 4.8, 5.1–5.2, 6.6. Updated 8 Jun 2026; verified 23 Aug 2026. Source of all UK dose figures, the NPIS instruction and the assay-interference statements.
2
DigiFab (Digoxin Immune Fab, Ovine) — US Prescribing Information, revised June 2017. digifab.health. Source of the ÷100 formula, the 0.5 mg per vial binding figure, the empiric 20-vial and 6-vial doses and the rapid potassium-drop warning. Included here because it differs materially from the UK label.
3
TOXBASE — digoxin; cardiac glycosides; digoxin-specific antibody fragments. National Poisons Information Service. toxbase.org (NHS login required. NPIS 0344 892 0111 — the UK SmPC directs that management be discussed with this service.)
4
Antman EM, Wenger TL, Butler VP Jr, Haber E, Smith TW. Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments: final report of a multicenter study. Circulation 1990;81(6):1744–52. PubMed
5
Eddleston M, Rajapakse S, Rajakanthan, et al. Anti-digoxin Fab fragments in cardiotoxicity induced by ingestion of yellow oleander: a randomised controlled trial. Lancet 2000;355(9208):967–72. PubMed The rare randomised evidence in this field, and it is in plant glycoside poisoning rather than digoxin.
6
Digoxin-specific antibody fragments — monograph. BNF, NICE. bnf.nice.org.uk

Digoxin immune Fab

At a glance