All posts by Adriana Garcia

Toxcard: DigiFab for Digoxin Toxicity

Author: Adriana Garcia, MD (Fidel Velázquez Sánchez Hospital) // Edited by: Cynthia Santos, MD (Senior Medical Toxicology Fellow, Emory University School of Medicine), Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)

toxcard
Case:

 A 73 y/o female with PMH of dementia, CHF, and atrial fibrillation presents with confusion, abdominal pain, nausea and vomiting. She is unable to provide a history due to her dementia and AMS. Vitals: BP 160/80 mmHg HR 60 T 36° RR 18. Her EKG demonstrates AV block. Na 140 K 5.3 Cl 105 CO2 20 BUN 40 Cr 2.1. Her digoxin level is 5ng/mL and she weighs 50 kg.

Question:

What dose of Digoxin-specific antibody fragments (DsFab) should you use? How do you administer it?

Pearl:

The dose of DsFab can be estimated in three ways 1) a formula if the dose is known 2) a formula if a serum digoxin level is known or 3) use of an empiric dose. 

1) If amount ingested is known:
  • In an acute overdose the # of vials can be calculated based on the ingested dose. Each vial neutralizes approximately 0.5mg of digoxin.[1,2]

Number of vials=   [(amount ingested in mg) x (0.8 bioavailability)]/(0.5 mg/vial)                                                                    

  • Note: The bioavailability for digoxin tablets is 0.8 and for digoxin capsules it is 1.[1]
  • The table below can also be used as a quick reference to calculate # of vials.
dig table
 Table source: www.drugs.com/pro/digibind.html
 
2) If serum digoxin level is known:

Number of vials=    [(serum digoxin level in ng/ml) x (weight in kg)]/100                                                                            

For our case, # of vials = 5 ng/ml x 50 kg/ 100 = 2.5

3) Emergent situations:

  • In an emergent situation involving an acute ingestion of unknown amount, 10 vials can be given initially for both adults and children. Observe for a response and can repeat with another 10 vials as needed. Monitor for volume overload in children.
  • In an emergent situation involving a chronic ingestion of unknown amount, 3-6 vials can be given for adults and 1-2 vials can be given for children.[1,2]

Indications for DsFab:

  • life-threatening dysrhythmia,
  • hyperkalemia: K+ > 5.0 mEq/L,
  • [digoxin] > 15 ng/ml at any time or > 10 ng/ml 6 hours post ingestion, regardless of clinical effects,
  • chronic elevation of [digoxin] associated with dysrhythmias, significant GI symptoms, or AMS,
  • acute ingestion of 10 mg in an adult or 4 mg in a child,
  • poisoning by non-digoxin cardiac glycoside. [2]

Note: In chronic poisoning, both the potassium and digoxin level may be NORMAL. In fact, it chronic overdoses the potassium level is often decreased.

Administrating DsFab:

  • Each 40mg vial of DigiFab (which binds 0.5 mg digoxin) should be reconstituted with 4 mL sterile water to yield an isosmotic solution with a concentration of 10 mg/mL.
  • The reconstituted solution can be diluted in normal saline to an appropriate volume for administration.
  • Infuse over at least 30 minutes.
  • If cardiac arrest is imminent a bolus injection can be given.
  • The reconstituted solution should be used immediately, if not it can be refrigerated and used within 4 hours.
  • Adverse effects of DigiFab include hypokalemia (K should be monitored frequently) and worsening atrial fibrillation or congestive heart failure. Anaphylaxis is rare.[1,3]
  • Measuring total serum digoxin concentration after DsFab will not be useful since it represents the free plus bound digoxin. Free digoxin concentrations are more clinically useful but they are more difficult to perform, sometimes erroneous  and are not readily available. The patient’s cardiac status should be monitored for signs of recurrent toxicity.[3]

Note: DsFab is only available in the U.S. as DigiFab since 2011. Previously, Digibind was available and used successfully but was discontinued in 2011 when DigiFab came on the market. They are both very similar except that DigiFab is prepared using the digoxin derivative as the hapten.[3]

Main point:

The # of vials of DsFab can be calculated based on the amount ingested for acute overdoses or the digoxin serum concentration in chronic overdoses. In emergent situations where the ingested dose or the serum level is unknown 10 – 20 vials is the recommended for acute ingestions and 3-6 vials for chronic ingestions. Each vial of Digoxin Fab should be reconstituted in 4 mL of sterile water and given slowly over at least 30 minutes. Unless in cardiac arrest, in which a bolus injection can be given. Watch out for hypokalemia and worsening a fib or CHF with Digoxin Fab administration. Don’t rely on measuring digoxin levels after giving DigiFab; the patient’s cardiac status should be monitored for signs of recurrent toxicity.

Reference:
  1. Micromedex Drug Information, Digoxin Immune Fab. Available at: http://micromedex.com/
  2. Hack J. Cardioactive steroids (Chapter). In Goldfrank’s Toxicological Emergencies, 11th edition (2015). Editors: Hoffman R, Howland M, Lewin N, Nelson L, Goldfrank L. McGraw Hill; New York.
  3. Howland M. Antidotes in depth: Digoxin-Specific Antibody Fragments (Chapter). In Goldfrank’s Toxicological Emergencies, 11th edition (2015). Editors: Hoffman R, Howland M, Lewin N, Nelson L, Goldfrank L. McGraw Hill; New York.