INTRODUCTION — Digoxin-specific antibody (Fab) fragments are the definitive treatment for patients with severe digitalis poisoning.

Prior to the advent of digoxin-specific antibodies, treatment for cardiac glycoside toxicity was largely supportive [1]. In 1976, antibody fragments were first used successfully to treat patients [2]. These antibodies are highly effective, safe, and widely used in clinical practice [3].

The dosing of digoxin-specific antibody (Fab) fragments based upon different clinical scenarios is discussed here. The indications for treatment with Fab fragments, the diagnosis and general management of digitalis poisoning, and the clinical use of digitalis are all reviewed separately. (See "Digitalis (cardiac glycoside) poisoning", section on 'Antidotal therapy with antibody (Fab) fragments' and "Control of ventricular rate in atrial fibrillation: Pharmacologic therapy", section on 'Digoxin' and "Treatment with digoxin: Initial dosing, monitoring, and dose modification" and "Secondary pharmacologic therapy in heart failure with reduced ejection fraction (HFrEF) in adults", section on 'Digoxin'.)

WHAT ARE FAB FRAGMENTS? — Digoxin-specific antibody (Fab) fragments are purified preparations consisting of the Fab portion of IgG antidigoxin antibodies derived from immunized sheep. These fragments bind free digoxin, thereby forming digoxin-immune fragment complexes. As the level of free digoxin in plasma falls, the resulting concentration gradient facilitates dissociation of digoxin from the sodium-potassium ATPase. Digoxin-immune fragment complexes are renally excreted. Because the size of the digoxin-immune complex molecule is large, hemodialysis is not an effective means of removal.

KINETICS AND ADVERSE EFFECTS OF FAB FRAGMENTS — Fab fragments are commercially available as DigiFab [4]. Each vial of DigiFab contains 40 mg of Fab fragments and binds approximately 0.5 mg of digoxin. DigiFab has an elimination half-life of approximately 15 to 20 hours. However, the half-life may be up to 10 times longer with renal impairment. The volume of distribution for DigiFab 0.3 L/kg.

Adverse effects of DigiFab include anaphylactic and anaphylactoid reactions, which are uncommon, as a Fab fragment lacks the immunogenic Fc portion of the antibody. However, patients with known allergies to sheep or sensitivity to papain or other papaya extracts used to cleave the antibody are at risk.

CALCULATING THE DOSE — The dose of DigiFab is determined by different methods, depending on the clinical scenario and information available. The indications for treatment with DigiFab are described separately. (See "Digitalis (cardiac glycoside) poisoning", section on 'Antidotal therapy with antibody (Fab) fragments'.)

Neither the digoxin level nor amount ingested is known — Empiric treatment in severe cases of toxicity when the amount of digoxin ingested is unknown consists of 10 vials of Fab fragments which should be repeated if clinical response is inadequate. Often small children can be adequately treated with smaller empiric doses and it is reasonable to start with 5 vials and escalate dose based on clinical response. When empiric dosing is required in very small children, concern for volume overload must be considered.

Amount of digoxin ingested is known but concentration is unknown — The number of Fab fragment vials to give the patient with an acute overdose, when only the amount ingested is known, is based upon the total body load:

●Step 1 – Calculate the total body load (TBL):

•TBL for digoxin = Dose (in mg) ingested x 0.8

(The value 0.8 reflects the bioavailability of digoxin)

●Step 2 – Number of vials = TBL/0.5

•(TBL/0.5 is identical to TBL x 2, which may be an easier calculation)

The number of vials should be rounded up to the nearest whole number. As an example, if the TBL is determined to be 3.125 mg, the number of vials is 3.125/0.5 = 6.25, which is rounded up to 7 vials.

Steady state digoxin concentration is known — The number of Fab fragment vials needed for treatment when the concentration is known is calculated based upon the drug concentration and the patient's weight:

●Number of vials = [(serum digoxin concentration in ng/mL) (patient's weight in kg)]/ 100

The number of vials should be rounded up to the nearest whole number. As an example, if a patient has a digoxin level of 6.7 ng/mL and weighs 65 kg, the number of vials would be (6.7 x 65)/100 = 4.4, which is rounded up to 5 vials.

This formula provides an accurate and quick estimate of the antidote needed for treatment. It is derived from a more complex pharmacokinetic calculation, which is available in the US Food and Drug Administration (FDA) prescribing information [4].

Note that the formula for calculating the number of Fab fragment vials needed based upon the serum concentration of digitoxin (which remains in use outside the United States) is not the same as that used for digoxin.

Cardiac glycoside poisoning other than digoxin or digitoxin — Quantitative serum levels obtained in poisonings from cardiac glycosides other than digoxin or digitoxin do not correlate with measurements of these drugs and cannot be used to calculate the Fab fragment dose. Therefore, empiric treatment is provided as if neither the amount ingested nor the concentration was known (10 vials initially). These are starting doses; they may be repeated if clinical response is inadequate after 30 minutes.

HOW TO ADMINISTER THE DRUG

Basic guidelines — Fab fragments should be given over 30 minutes in all patients except those in cardiac arrest or in whom arrest is imminent. In such patients, the Fab fragments can be given as a slow IV push. It is important to emphasize that after Fab fragments are administered total serum digoxin concentrations will be unreliable; only free or unbound digoxin levels will be clinically useful.

Chronic toxicity without severe signs — In individuals with chronic toxicity who do not manifest immediately life-threatening arrhythmias (eg, AV nodal blockade present on ECG, but patient maintains normal blood pressure and clear mentation), half the recommended dose can be given initially in order to avoid unmasking the condition for which the patient is taking digoxin. Giving a full dose can elicit acute decompensated heart failure or atrial fibrillation with rapid ventricular response.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: General measures for acute poisoning treatment".)

SUMMARY AND RECOMMENDATIONS

●Digoxin-specific antibody (Fab) fragments consist of the Fab portion of IgG antidigoxin antibodies. These fragments bind free digoxin, thereby forming digoxin-immune fragment complexes. As the level of free digoxin in plasma falls, the resulting concentration gradient facilitates dissociation of digoxin from the sodium-potassium ATPase. Fab fragment complexes are renally excreted. (See 'What are Fab fragments?' above.)

●The dosing of Fab fragments is based upon the clinical scenario, including whether the amount of digoxin ingested or the serum digoxin concentration is known. Three dosing regimens and guidance for administering the drug are described in the text. (See 'Calculating the dose' above and 'How to administer the drug' above.)