digoxin immune Fab (ovine)
Digibind, DigiFab

Available forms
Available by prescription only
Injection: 38-mg vial

Indications and dosages
 Potentially life-threatening digoxin or digitoxin intoxication. Adults and children: Administered I.V. over 30 minutes or as a bolus if cardiac arrest is imminent. Dosage varies based on amount of drug to be neutralized; average dose for adults is 6 vials (228 mg). However, if toxicity resulted from acute digoxin ingestion and neither a serum digoxin level nor an estimated ingestion amount is known, 10 to 20 vials (380 to 760 mg) should be administered. See package insert for complete, specific dosage instructions.

Pharmacodynamics
Cardiac glycoside antidote action: Specific antigen-binding fragments bind to free digoxin in extracellular fluid and intravascularly to prevent and reverse pharmacologic and toxic effects of the cardiac glycoside. This binding is preferential for digoxin and digitoxin; preliminary evidence suggests some binding to other digoxin derivatives and cardioactive metabolites.
 Once free digoxin is bound and removed from serum, tissue-bound digoxin is released into the serum to maintain efflux-influx balance. As digoxin is released, it’s bound and removed by digoxin immune Fab, resulting in a reduction of serum and tissue digoxin. Cardiac glycoside toxicity begins to subside within 30 minutes after completion of a 15- to 30-minute I.V. infusion of digoxin immune Fab. The onset of action and response is variable and appears to depend on rate of infusion, dose administered relative to body load of glycoside, and possibly other, as yet unidentified, factors. Reversal of toxicity, including hyperkalemia, is usually complete within 2 to 6 hours after administration of digoxin immune Fab.

Pharmacokinetics
Absorption: Administered I.V.
Distribution: Distribution isn’t fully characterized. After I.V. administration, drug appears to be distributed rapidly throughout extracellular space, into both plasma and interstitial fluid. It isn’t known whether digoxin immune Fab crosses the placental barrier or appears in breast milk.
Metabolism: Unknown.
Excretion: Excreted in urine via glomerular filtration.

Contraindications and precautions
No known contraindications. Use cautiously in patients known to be allergic to ovine proteins. In these high-risk patients, skin testing is recommended because drug is derived from digoxin-specific antibody fragments obtained from immunized sheep.

Interactions
Drug-drug. Cardiac glycosides, including digoxin, digitoxin, and lanatoside C: When used together, digoxin immune Fab binds cardiac glycosides. This also occurs if redigitalization is attempted before elimination of digoxin immune Fab is complete (several days with normal renal function; 1 week or longer with renal impairment). Drug is used for this effect.

Adverse reactions
CV: heart failure, rapid ventricular rate (both caused by reversal of cardiac glycoside’s therapeutic effects), low cardiac output, atrial fibrillation.
Metabolic: hypokalemia.
Other: hypersensitivity reactions (anaphylaxis).

Effects on lab test results
• May decrease potassium levels.

Overdose and treatment
Limited information is available. However, administration of doses larger than needed for neutralizing the cardiac glycoside may subject patient to increased risk of allergic or febrile reaction or delayed serum sickness. Large doses may also prolong the time span needed before redigitalization.

Special considerations
• Digoxin immune Fab therapy alters standard cardiac glycoside determinations by radioimmunoassay procedures. Results may be falsely increased or decreased, depending on separation method used. Serum potassium levels may decrease rapidly.
• Measure serum digoxin or digitoxin levels before giving antidote because serum levels may be difficult to interpret after therapy with antidote.
• Give I.V. using a 0.22-micron filter needle over 30 minutes or as a bolus injection when cardiac arrest is imminent. Dose depends on amount of digoxin to be neutralized. Each 38-mg vial binds about 0.5 mg of digoxin or digitoxin. Reconstitute vial with 4 ml of sterile water for injection, mix gently, and use immediately. May be stored in refrigerator up to 4 hours.
• To determine appropriate dose, divide the total digitalis body load by 0.5; the resultant number estimates the number of vials required for appropriate dose. Or, in cases of acute ingestion of known quantity of digitalis, multiply the amount of digitalis ingested in milligrams by 0.80 (to account for incomplete absorption).
• Skin testing may be appropriate for high-risk patients. One of two methods may be used:
-Intradermal test: Dilute 0.1 ml of reconstituted solution in 9.9 ml of sterile saline for injection; then withdraw and inject 0.1 ml of this solution intradermally. Inspect site after 20 minutes for signs of erythema or urticaria.
-Scratch test: Dilute as for intradermal test. Place one drop of diluted solution on skin and make a 1/4" scratch through the drop with a sterile needle. Inspect site after 20 minutes for signs of erythema or urticaria. If results are positive, avoid use of digoxin immune Fab unless needed. If systemic reaction occurs, treat symptomatically.
• Pretreat patients with sensitivity or allergy to sheep or ovine products, or when skin test results are positive, with an antihistamine such as diphenhydramine and a corticosteroid before administering digoxin immune Fab.
 ALERT Keep drugs and equipment for resuscitation readily available during administration of digoxin immune Fab for patients who respond poorly to withdrawal of inotropic effects of digoxin. Dopamine or dobutamine, or other cardiac load-reducing agents, may be used. Catecholamines may aggravate arrhythmias induced by digitalis toxicity; use cautiously.
• Closely monitor temperature, blood pressure, ECG, and potassium level before, during, and after administration of antidote.
• Potassium levels must be checked repeatedly because severe digitalis intoxication can cause life-threatening hyperkalemia, and reversal by digoxin immune Fab may lead to rapid hypokalemia.
Breast-feeding patients
• It isn’t known whether digoxin immune Fab appears in breast milk; use cautiously in breast-feeding women.
Pediatric patients
• Consider the risks and the potential benefits. Adverse effects haven’t occurred in infants and small children. Watch for volume overload in small children. Very small doses may require diluting reconstituted solution with 36 ml of sterile saline for injection to produce a 1 mg/ml solution.
• Infants may need smaller doses; manufacturer recommends reconstituting as directed and administering with a tuberculin syringe.

Patient education
• Explain use and administration to patient and family.
• Instruct patient to report adverse effects immediately.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use