toxcard

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)

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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.

4 thoughts on “Toxcard: DigiFab for Digoxin Toxicity”

  1. thanks for the post. A quick recap of usual signs/symptoms of digoxin toxicity would be good here. Especially when the case given had such a non specific presentation.

    1. Thanks for reading, and thanks for the comments! I’m glad you bring this up, as digoxin toxicity is a difficult diagnosis. We will be covering this in a future Tox Card.

  2. A couple of comments:

    10 vial empiric dosing is typically note feasible or necessary. Most hospitals, even large academic centers do not stock 10 vials. Patients rarely require more than 4. While most texts note 10 vial empiric dosing, clinical experience shows that 4 is more appropriate.
    Some have suggested that half dosing of digoxin specific antibodies is just as efficacious as full dosing in chronic adult digoxin toxicity. Especially if patients with severely reduced LVEF, we don’t need to reverse ALL the digoxin (and theoretically could precipitate CHF exacerbation). The goal is just to get back to a therapeutic range. You may want to reference that.

    1. That is a good point, most digoxin toxicity cases probably don’t need the full empiric dosing. However, I believe this empiric dosing is meant to be used for emergent life threatening situations where the patient ingested very large doses (likely suicidal/intentional) and has moribund conditions like severe hyperkalemia or ventricular dysrhythmias, and shock. In these situations history is limited so obtaining the dose ingested is often impossible and waiting for the dig level to come back before treating is dangerous. In these rare extreme situations completely reversing digoxin’s effects is the primary aim and inotropes can be used to help treat CHF. Also, since many residents and medical students use FOAM as a supplemental educational resource I think it is important to use recommendations that are in most textbooks and established drug resources. These are the recommendations that are in Goldfrank’s, Micromedex, and many other established resources. A common complaint with FOAM is that residents don’t learn the basic primary literature and instead end up learning someone’s clinical experience or opinion on the subject. This is not entirely a bad thing since residents may lack clinical experience and hence can learn some tricks of the trade through FOAM. However, the purpose of this toxcards series is to help distill toxicology concepts that they will find in textbooks, drug resources, and in their board exams. Thanks for your comment, it illustrates that this issue is complicated and clinical experience is key too.

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