Simplified Dosing Scheme for DigiFab® in Acute Digoxin Poisoning

Background

Treatment of digoxin toxicity can be quite complex and generally involves the use of digoxin immune Fab (DigiFab®) for symptomatic patients. The dosing of DigiFab can vary depending on the amount ingested, serum concentration, and/or suspected chronicity of toxicity. Alternatively, for an acute ingested of an unknown amount where the serum concentration is not available, it is recommended that 10 vials of DigiFab be administered empirically. This antidote is expensive (~$5,000 per vial) and not always readily available in every hospital. Given the complicated dosing and cost, alternative dosing strategies are being explored.

Evidence

Researchers from Australia first proposed an initial 2-vial DigiFab dose for acute digoxin poisoning in a 2014 review article [1]. They followed this up with a pharmacokinetic study supporting the simplified dosing scheme [2]. Based on their early data, the Australian poison center recommendations were revised to instead use small doses of DigiFab (2 vials at a time) with repeat doses as needed to achieve clinical effect. This allowed them to prospectively study this new dosing strategy in 21 cases of digoxin toxicity [3]. Most patients required less than would have been administered following traditional dosing calculations. Patients receiving the lower-dosing scheme did have a rebound in free digoxin levels >2 ng/mL at a median time of 18 hours in patients with normal renal function and 103 hours in patients with an acute kidney injury. Most patients received 2 vials of DigiFab initially and a median of 4 vials total after receiving additional doses based on persistent or recurrent symptoms. Overall, patients required significantly less antidote with similar clinical outcomes. Importantly, there are limitations with the data to date, highlighted in a letter-to-the-editor (Mahonski 2021). This titration approach should only be considered with input from a toxicologist.

Characteristics and Savings
Amount of digoxin ingested*13 mg (9.5-25 mg)
Initial potassium*5 mEq/L (4.5-5.4 mEq/L)
Fatalities due to digoxin toxicity0
Estimated vials saved^223-356 vials
Estimated cost savings^†$1.1-1.8 million
* Median (IQR)
^ Difference between titrated dosing scheme compared to doses based on ingested amount and serum concentration
† Based on cost of $5000 per vial

Pearls

Following administration of DigiFab, avoid measurement of the total digoxin concentration as this measures both free drug and drug bound to DigiFab, which will cause the result to be falsely elevated [4]. Additionally, extracorporeal treatments are not recommended for the removal of digoxin or the digoxin-Fab complex, regardless of the clinical context.

Bottom Line

  • In select cases of acute digoxin poisoning, patients may safely receive 2 vials of DigiFab with repeat doses as necessary based on symptoms. If considering this treatment approach, it is recommended to consult with a toxicologist and/or pharmacist.
  • Total serum digoxin levels can be falsely elevated following the administration of DigiFab.

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References

  1. Chan BSH, Buckley NA. Digoxin-specific antibody fragments in the treatment of digoxin toxicity. Clin Toxicol (Phila). 2014;52(8):824-836. doi: 10.3109/15563650.2014.943907. PMID: 25089630.
  2. Bracken LM, Chan BSH, Buckley NA. Physiologically based pharmacokinetic modelling of acute digoxin toxicity and the effect of digoxin-specific antibody fragments. Clin Toxicol (Phila). 2019;57(2):117-124. doi: 10.1080/15563650.2018.1503288. PMID: 30306803.
  3. Chan BS, Isbister GK, Chiew A, Isoardi K, Buckley NA. Clinical experience with titrating doses of digoxin antibodies in acute digoxin poisoning. (ATOM-6). Clin Toxicol (Phila). Published online August 23, 2021:1-7. doi: 10.1080/15563650.2021.1968422. PMID: 34424803.
  4. DigiFab®. Package insert. BTG International Inc; 2017.
  5. Mowry JB, Burdmann EA, Anseeuw K, et al. Extracorporeal treatment for digoxin poisoning: systematic review and recommendations from the EXTRIP Workgroup. Clin Toxicol (Phila). 2016;54(2):103-114. doi: 10.3109/15563650.2015.1118488. PMID: 26795743.
Bryan D. Hayes, PharmD, DABAT, FAACT, FASHP

Bryan D. Hayes, PharmD, DABAT, FAACT, FASHP

Leadership Team, ALiEM
Creator and Lead Editor, Capsules and EM Pharm Pearls Series
Attending Pharmacist, EM and Toxicology, MGH
Associate Professor of EM, Division of Medical Toxicology, Harvard Medical School
Bryan D. Hayes, PharmD, DABAT, FAACT, FASHP

@PharmERToxGuy

EM Pharmacist & Toxicologist @MassGeneralEM | Asst Prof @HarvardMed/@EMRES_MGHBWH | @ALiEMteam leadership | Capsules creator, ALiEMU | President, ABAT | #FOAMed
Mike O'Brien, PharmD

Mike O'Brien, PharmD

ALiEM Series Editor, EM Pharm Pearls
EM Clinical Pharmacist
Massachusetts General Hospital
Mike O'Brien, PharmD

@MikeEMPharmD

Emergency Medicine Pharmacist at MGH | #FOAMed | Thoughts & views are my own