Digibind Antidote

Review and revised 11 July 2014

OVERVIEW

• Digibind is the trade name for a digoxin antidote containing Digoxin-specific antibody Fab fragments
• there is often a reluctance to give digibind due to cost and underestimating the mortality associated with digoxin toxicity, however  it is prudent to administer digibind based on a considered risk assessment and before the life-threatening manifestations of digoxin toxicity develop
• digoxin levels cannot be accurately measured for about 3 weeks after administration of digibind, as they will be artefactually high given that most serum digoxin assays measure both free and digibind-bound digoxin in the circulation (some laboratories may be able to measure free digoxin levels specifically)
• supplies of digibind should be available on site in the emergency department, and in severe toxicities early steps to source more may be necessary

CLASS

• Digoxin-specific antibody Fab fragments

MECHANISM OF ACTION

• digibind has a much higher affinity (high affinity (10⁹–10¹⁰ L/mol) for digoxin than the Na+/K+ ATPase digoxin receptor site
• binds to digoxin in the extracellular spaces preventing digoxin binding to the Na+/K+ ATPase
• creates a concentration gradient that extracts digoxin from the intracellular space
• bound digoxin is then renally eliminated with digibind

PHARMACEUTICS

• powder
• contains 38mg of digoxin-specific Fab fragments
• reconstitute with sterile water

DOSE

• each 38mg vial will bind about 0.5mg of digoxin
• give over 30min or bolus if in an arrest
• improvement in symptoms usually within 30 min, with maximal effect by 4 hours

Acute digoxin toxicity

• Known dose:
  • number of vials = Ingested dose (mg) x 0.8 (bioavailability) x 2 (note that 0.8 represents the 80% oral bioavailability of digoxin)
• Unknown dose:

• Give 5 vials initially if the patient is hemodynamically stable
• Give 10 vials initially if the patient is hemodynamically unstable
• Repeat doses of 5 ampoules should be given every 30 minutes until reversal of digoxin toxicity is achieved
• In cardiac arrest give 20 vials (760 mg), or as many vials as are available if <20 stocked

Chronic digoxin toxicity

• Known level: number of vials required = post-distribution serum digoxin concentration (nanogram/mL) x weight (kg)/100 (multiply by 0.78 if SI units are used for post-distribution serum digoxin concentration)
• empiric dosing: give 2 ampoules and observe for clinical response, if toxicity remains after 30 minutes give a further 2 ampoules
• a source of confusion is the units of measurement used by laboratories: many laboratories measurs serum digoxin levels in nmols/L. The conversion factor is ng/ml x 1.28 = nmols/L

Endpoints

• resolution of nausa and vomiting
• resolution of dysrhythmia
• complete binding of total body digoxin is usually not necessary to control digoxin toxicity

INDICATIONS

Acute digoxin toxicity

•  cardiac arrest
• life-threatening dysrhythmia
• K >5mM
• >10mg ingested (adult), >4mg ingested (child)
• >15 nM level (>12ng/mL)

Chronic digoxin toxicity

•  cardiac arrest
• life-threatening dysrhythmia
• dysrhythmia or increased automaticity unlikely to be tolerated for a prolonged period
• significant gastrointestinal symptoms
• symptoms of digoxin toxicity and coexistent renal failure

Other life-threatening cardiac glycoside toxicities:

• oleander poisoning
• cane toad poisoning (bufotoxin)
• Chinese medicines (e.g. Chan Su, Dan Shen and Lu-Shen-Wan)

No absolute contraindications

ADVERSE EFFECTS

• anaphylaxis (rare)
• effects from withdrawal of digoxin: AF, heart failure (negative inotropy), hypokalemia

PHARMACOKINETICS

• Absorption – IV administration, from the end of infusion  initial response is 20 minutes (0 to 60 min) and maximal response is at 90 minutes (30-360 min)
• Distribution – large Vd
• Metabolism – nil
• Elimination – urinary, t ½ = 11 hrs; bound digoxin has an elimination t1/2 of 16-30h

References

LITFL

• CCC – Digoxin
• CCC – Digoxin Toxicity
• ECG library – Digoxin Effect
• ECG library – Digoxin Toxicity
• CCC – Digibind / Digoxin-specific Fab Fragments
• CCC – Calcium, Digoxin Toxicity and ‘Stone Heart’ Theory

Journal articles and textbooks

• 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 Jun;81(6):1744-52
• McMillin GA, Owen WE, Lambert TL, De BK, Frank EL, Bach PR, Annesley TM, Roberts WL. Comparable effects of DIGIBIND and DigiFab in thirteen digoxin immunoassays. Clin Chem. 2002 Sep;48(9):1580-4.
• Ip D, Syed H, Cohen M. Digoxin specific antibody fragments (Digibind) in digoxin toxicity. BMJ. 2009 Sep 3;339:b2884
• Pincus M. Management of digoxin toxicity. Aust Prescr. 2016 Feb;39(1):18-20. doi: 10.18773/austprescr.2016.006.

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