Version July 2025
INTRODUCTION —
Digoxin-specific antibody (Fab) fragments are the definitive treatment for patients with severe cardiac glycoside (eg, digoxin) 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 Fab fragments based upon different clinical scenarios is discussed here. The indications for treatment with Fab fragments, the diagnosis and general management of cardiac glycoside poisoning, and the clinical use of digoxin are all reviewed separately.
●(See "Treatment with digoxin: Initial dosing, monitoring, and dose modification".)
WHAT ARE FAB FRAGMENTS? —
Digoxin immune Fab fragments are purified preparations consisting of the Fab portion of IgG anti-digoxin antibodies derived from immunized sheep. These fragments bind free digoxin, thereby forming digoxin-immune fragment complexes. As the concentration 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 of the large size of both digoxin and the digoxin-immune complex, neither is effectively cleared by hemodialysis.
KINETICS AND ADVERSE EFFECTS OF FAB FRAGMENTS —
Digoxin immune Fab is commercially available as DigiFab [4]. Each vial of digoxin immune Fab contains 40 mg of Fab fragments and binds approximately 0.5 mg of digoxin. Digoxin immune Fab has an elimination half-life of approximately 15 to 20 hours. However, the half-life may be up to 10 times longer with kidney function impairment. The volume of distribution for digoxin immune Fab is 0.3 L/kg.
Hypersensitivity reactions are the primary adverse effects of digoxin immune Fab. Although uncommon, patients with known allergies to sheep or sensitivity to papain or other papaya extracts used to cleave the antibody are at highest risk.
Use of digoxin immune Fab may result in complete reversal of cardiac glycoside effects, precipitating an acute congestive heart failure exacerbation or loss of rate control in patients with atrial fibrillation.
CALCULATING THE DOSE —
The dose of digoxin immune Fab is determined by different methods depending on the clinical scenario and information available. The indications for treatment with digoxin immune Fab are described separately. (See "Digitalis (cardiac glycoside) poisoning", section on 'Antidotal therapy with antibody (Fab) fragments'.)
Neither the digoxin concentration nor amount ingested is known — Treatment in cases of severe toxicity when the amount of digoxin ingested is unknown consists of empiric Fab fragment dosing. Our approach depends on whether cardiac arrest appears imminent.
●Patient with relative hemodynamic stability – Most patients with digoxin poisoning are relatively stable, and arrest is not imminent. In such patients, we administer two vials of digoxin immune Fab over 30 minutes [5,6]. If clinical response is inadequate, then an additional one to two vials are administered.
●Patient in cardiac arrest or cardiac arrest appears imminent – The traditional empiric dosing strategy of 10 vials of digoxin immune Fab in adults or five vials in children administered by slow intravenous (IV) push is reasonable [4]. The initial dose can be repeated if there is inadequate clinical response (although at this time, it is reasonable to reconsider the diagnosis of cardiac glycoside toxicity). 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 digoxin immune Fab vials to give the patient with an acute overdose, when only the amount ingested is known, is based upon the total body load (TBL):
●Step 1 – Calculate the 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. Alternatively, the number of vials (rounded up to whole number) can be calculated as dose (in mg) ingested x 1.6 [which is 0.8/0.5].
Steady state digoxin concentration is known — The number of digoxin immune Fab vials needed for treatment (ie, full reversal of digoxin effects) when the post-distribution 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 concentration of 4.4 ng/mL and weighs 65 kg, the number of vials would be (4.4 x 65)/100 = 2.86, which is rounded up to 3 vials. This formula provides an accurate and quick estimate of the antidote needed for treatment and is derived from a more complex pharmacokinetic calculation [4].
Partial reversal of digoxin effects can be accomplished by providing half the calculated number of vials using the equation above. This approach is reasonable when concerned that full reversal may precipitate an acute congestive heart failure exacerbation or loss of rate control in atrial fibrillation (eg, patient with baseline reduced ejection fraction).
Note that the formula for calculating the number of digoxin immune Fab vials needed is based upon the serum concentration of digoxin and is not the same as any other commercially available agent (eg, digitoxin).
Cardiac glycoside poisoning other than digoxin — Quantitative serum concentrations obtained following poisonings from cardiac glycosides other than digoxin (eg, naturally occurring cardenolides or bufadienolides) do not correlate and cannot be used to calculate the digoxin immune Fab dose. Therefore, empiric dosing is recommended (10 vials initially) in these circumstances. Repeat doses may be needed if clinical response is inadequate.
HOW TO ADMINISTER THE DRUG
Basic guidelines — Digoxin immune Fab should be given over 30 minutes in all patients except those in cardiac arrest or in whom arrest is imminent. In such patients, the digoxin immune Fab can be given as a slow intravenous (IV) push. It is important to emphasize that after digoxin immune Fab is administered, total serum digoxin concentrations will be unreliable and should no longer be obtained or used for clinical decision making. If available, free or unbound digoxin concentrations will be clinically useful.
Chronic toxicity without severe signs — In individuals with chronic toxicity meeting criteria for antidotal therapy but without immediately life-threatening dysrhythmias, 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. Therefore, in the setting of chronic toxicity, the decision to proceed with a full reversal dose of digoxin immune Fab must be made following appropriate risk-benefit analysis.
ADDITIONAL RESOURCES
Regional poison centers — Regional poison centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison centers".)
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
●Mechanism of action – Digoxin-specific antibody (Fab) fragments bind free digoxin, forming digoxin-immune fragment complexes. As the concentration 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.)
●Dosing regimens – The dosing of digoxin immune Fab is based upon the clinical scenario, including whether the amount of digoxin ingested or the serum digoxin concentration is known. (See 'Calculating the dose' above and 'How to administer the drug' above.)
•Known steady state digoxin concentration (see 'Steady state digoxin concentration is known' above):
-Full reversal of digoxin effects: Number of vials (rounded up to whole number) = [(serum digoxin concentration in ng/mL)(patient's weight in kg)]/100
-Partial reversal of digoxin effects: Half the number of vials calculated from the full reversal of digoxin effects formula above
•Neither digoxin concentration nor amount ingested is known (see 'Neither the digoxin concentration nor amount ingested is known' above):
-In patients with relative hemodynamic stability, we administer two vials of digoxin immune Fab, each over 30 minutes, and repeat based on clinical response.
-In patients in cardiac arrest or if cardiac arrest appears imminent, empiric dosing of 10 vials of digoxin immune Fab in adults or five vials in children is given by slow intravenous (IV) push. Dosing can be repeated if there is inadequate clinical response, although alternative diagnosis must be considered.
•Ingested digoxin amount is known but concentration unknown: Number of vials (rounded up to whole number) = Dose (in mg) ingested x 1.6 (see 'Amount of digoxin ingested is known but concentration is unknown' above)
