DESCRIPTION

• Digoxin immune Fab is an antidote used for toxicity from cardiac glycosides.
• Digoxin Fab is a purified Fab antibody that specifically binds the cardiac glycosides, digoxin, and digitoxin, forming a Fab-digoxin complex that terminates the activity of digoxin. It also binds cardiac glycosides from some plants and animals.

FORMS AND USES

Digoxin immune Fab (Digibind) is provided lyophilized in vials containing 40 mg of Fab/vial.

MECHANISM OF ACTION

• The concentration of free digoxin in the intravascular compartment becomes virtually zero since any free digoxin becomes bound to digoxin Fab.
• Toad toxins contain compounds similar to digitalis glycosides and have been successfully treated in some cases by digoxin Fab.

DRUG AND DISEASE INTERACTIONS

Depending on the dose, digoxin immune Fab also terminates the desired therapeutic effects of digoxin or digitoxin and may allow recurrence of underlying rapid ventricular response or congestive heart failure.

PREGNANCY AND LACTATION

• US FDA Pregnancy Category C. The drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in either animals or women.
• Digoxin Fab should be used in pregnant women as it is used in other adult patients.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• MECHANISM OF ACTION
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

DIGOXIN OR DIGITOXIN TOXICITY

• Signs of cardiovascular instability, including hypotension, symptomatic bradycardia, and other potentially unstable dysrhythmias.
• Rapid progression of toxicity, including gastrointestinal or cardiovascular symptoms.
• Hyperkalemia greater than 5.5 mEq/L without other major effects (associated with a poor prognosis).

OTHER CARDIAC GLYCOSIDES (PLANT, APHRODISIAC, OR TOAD SECRETIONS)

• Digoxin immune Fab has been useful for cardiac toxicity induced by plant cardiac glycosides (e.g., oleander and lanatoside C), certain aphrodisiacs (e.g., Rock Hard and Love Stone), and some abused animal products (Bufo toad species).
• A therapeutic trial in patients with cardiac effects following ingestion of these products is warranted (see SECTION IV, Plants—Cardiac Glycosides chapter).

Section Outline:

• DIGOXIN OR DIGITOXIN TOXICITY
• OTHER CARDIAC GLYCOSIDES (PLANT, APHRODISIAC, OR TOAD SECRETIONS)

CONTRAINDICATIONS

Allergy to sheep products contraindicates use (a history of skin irritation to wool products does not constitute an allergy).

ADVERSE EFFECTS

• Allergic reactions to digoxin Fab may occur; however, they have been rare and mild.
• Hypokalemia may develop rapidly; patients with a low or borderline potassium level should receive supplemental potassium during treatment with digoxin immune Fab.
• Loss of digoxin effect may occur; for example, loss of rate control in atrial fibrillation could occur.

Section Outline:

• CONTRAINDICATIONS
• ADVERSE EFFECTS

• If both the amount ingested and the serum digoxin levels are unknown, digoxin immune Fab can be administered empirically.
  • Acute single ingestion. The manufacturer recommends that 20 vials be administered for acute adult or pediatric overdoses. However, most authorities recommend 10 vials as the initial dose with subsequent therapy as needed.
  • Chronic digitalis intoxication. The recommended empiric dose is two to three vials for adults and 1/4 to 1/2 vial for a small child.
• If only the amount of digoxin ingested is known.
  • The following calculation is used:
    • Amount ingested (mg) × [bioavailability/0.6 mg] = dose of Fab in vials
    • The bioavailability of digoxin tablets is 0.8, but is 1.0 for the capsule (Lanoxicaps) and varies for other preparations. If the bioavailability is unknown, the value of 0.8 should be used. Each vial of digoxin immune Fab neutralizes 0.6 mg of digoxin.
    • For example, the dose for ingestion of ten 0.25 mg tablets is: 2.5 mg × (0.8/0.6) = 3.3 vials.
• If a 6-hour or greater postingestion serum concentration is available.
  • The following calculation is used:
    • [serum concentration of digoxin (µg/ml) × 6 L/kg × patient weight (kg)]/[1,000 × 0.6 mg] = number of vials
    • The volume of distribution of digitalis is 6 L/kg.
    • The serum level should be drawn at least 6 hours postingestion.
    • If the patient is dependent on digitalis for cardiac stability, this calculation can be modified to maintain the serum level of unbound digitalis at 1.0. In this modified calculation, the "serum concentration of digoxin" is then reduced to 1.0 µg/ml.
• If other cardiac glycoside, plant, aphrodisiac, or food secretion has been ingested, the dose is unknown.
  • In case reports treatment has typically started with 5 to 10 vials.
  • Additional doses may be necessary. However, it is unlikely that all cardiac glycosides in these products are neutralized by digoxin immune Fab; therefore, if no apparent response is obtained, there should be no delay in using alternative treatments.

• When calculating the required dose of digoxin immune Fab from the serum digoxin concentration, a serum digoxin level drawn earlier than 6 hours after the last digoxin dose is difficult to interpret. Distribution of digoxin requires at least 6 hours, and levels drawn earlier than this will be higher than the actual blood concentration and should not be used in calculating digoxin immune Fab doses.
• Patients who rely on digoxin for medical reasons, such as rate control of atrial fibrillation, should probably not have their entire serum digoxin load reversed with digoxin immune Fab.
  • Doing so could make the patient medically unstable.
  • Thus, partial neutralization may be a safer method to reverse a specific amount of digoxin.
• Digoxin toxicity has recurred in patients with renal failure who received digoxin immune Fab.
  • The Fab-digoxin complex begins to dissociate about 3 days after administration of digoxin immune Fab.
  • If a significant portion of the complex remains unexcreted a week after administration due to renal insufficiency, toxicity may recur.
• If the initial dose of digoxin immune Fab is inadequate, digoxin toxicity may recur within a few hours of the administration of digoxin immune Fab. This is not dangerous if it is anticipated and monitored. Additional digoxin immune Fab should be administered if clinical effects recur.
• Digoxin-like immunoreactive substances are endogenous substances that may be detected by digoxin assays.
  • They have been reported in neonates, and rarely in pregnant women or patients with renal or hepatic failure.
  • Although it produces a high apparent digoxin level, clinically apparent toxic effects should not be present.
• The elderly with cardiac problems may be more likely to succumb to digoxin toxicity and should therefore be more readily treated.

ICD-9-CM 972.1

Poisoning by agents primarily affecting the cardiovascular system: cardiotonic glycosides and drugs of similar action.

RECOMMENDED READING

Taboulet P, Baud FJ, Bismuth C. Clinical features and management of digitalis poisoning: rationale for immunotherapy. Clin Tox 1993;31:247-260.

Woolf AD, Wenger T, Smith TW, et al. The use of digoxin-specific Fab fragments for severe digitalis intoxication in children. N Engl J Med 1992;326:1739-1744.

Authors: Lada Kokan and Kennon Heard

Reviewer: Richard C. Dart