Digoxin Poisoning Management – Pharmacy & Acute Care University

Digoxin is a cardioactive glycoside indicated for atrial flutter, atrial fibrillation, and heart failure
Acts as a sodium/potassium pump inhibitor for cardiac myocytes → toxicity arises with too much intracellular Na+ inhibiting the sodium/calcium pump from working properly (increasing intracellular calcium)
- Increased inotropy within the cardiac myocytes → dysrhythmias
EKG abnormalities: premature ventricular contractions, biphasic T wave, shortened QT interval, AV block
Digoxin therapeutic levels range from 0.8-2.0 ng/ml (toxicity can begin >2 ng/ml)

Pharmacology

	Digoxin Immune Fab (DigiFab or DigiBind)
Dose	1 vial = 40mg (binds to 0.5mg of digoxin) Unknown toxicity level: Initial 10vials Vials = Total body load (mg) x 2 For chronic ingestion of unknown amount 3-6 vials can be given for adults 1-2 vials can be given for children
Administration	IV infusion over 30 minutes If cardiac arrest is imminent a bolus injection can be given
PK/PD	Onset: 20-90 minutes Duration of action: 15 – 20 hrs
Adverse Effects	Orthostatic hypotension, ventricular tachycardia, hypokalemia
Mechanism of Action	Immune antigen-binding fragments that rapidly bind with digoxin to decrease free digoxin levels within the body
Compatibility	0.9% NS Only
Comments	Monitor K+ closely as it shifts intracellularly potentially causing hypokalemia.Total concentration of digoxin may be falsely elevated after administration due to in free drug & bounded drug.Free digoxin concentrations are more clinically useful

Overview of Evidence

Author, year	Design/ sample size	Intervention & Comparison	Outcome
Wei et al., 2021	Case reports (n=121)	DigiBind vs DigiFab adverse events reported to FAERS from 1986-2019	87.2% of DigiBind reports were serious AEs vs. 62.8% of DigiFabHypotension, cardiac arrest, and death were among the most serious AEs
Ward et al, 2000	Observational (n=16)	DigiBind vs DigiFab in healthy volunteers	Both Fab products reduced free digoxin serum concentrations to below assay detection Total digoxin serum concentrations increased approximately 10-fold (indicated fab product binding digoxin)
Renard et al., 1997	Observational (n=16)	Influence of age & renal dysfunction on digoxin-specific Fab pharmacokinetics •Doses 80-800mg infused over 0.25-2hr •Patients aged 35-90 with CrCl 10.6-122.1 ml/min	Linear decrease of total body clearance is linked to renal function and age, but not VdPlasma half-lives ranged from 11-34.5hrsAll patients recovered and no adverse effects were reported
Antman et al., 1990	Open-label trial (n=150)	Digoxin-specific Fab fragment dosed based on total ingested amount (mg) or digoxin serum concentration (ng/ml)	90% of patient toxicity resolved or improved with 10% showing no response Median dose ~ 200mg (5 vials)Highest dose ~ 1600mg (40 vials)

Conclusions

Digoxin toxicity is a serious & life-threatening condition if not appropriately reversed by an available antidote
For unknown amount of ingestion, administer 10 vials of digoxin Immune Fab to treat digoxin toxicity
Age and renal function are proven not to be factors prohibiting digoxin toxicity treatment

References

Bismuth C, Gaultier M, Conso F, Efthymiou ML. Hyperkalemia in acute digitalis poisoning: prognostic significance and therapeutic implications. Clin Toxicol. 1973;6(2):153-162. doi:10.3109/15563657308990513
David MNV, Shetty M. Digoxin. [Updated 2022 Sep 5]. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK556025/
Lexicomp Online, Lexi-Drugs Online. Waltham, MA: UpToDate, Inc.; January 2023. Accessed January 16, 2023. https://online.lexi.com.
Antman et al. Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments. Final report of a multicenter study. Circulation. 1990;81(6):1744-1752. doi:10.1161/01.cir.81.6.1744
Renard C, Grene-Lerouge N, Beau N, Baud F, Scherrmann JM. Pharmacokinetics of digoxin-specific Fab: effects of decreased renal function and age. Br J Clin Pharmacol. 1997;44(2):135-138. doi:10.1046/j.1365-2125.1997.00654.x
Roberts DM, Gallapatthy G, Dunuwille A, Chan BS. Pharmacological treatment of cardiac glycoside poisoning. Br J Clin Pharmacol. 2016;81(3):488-495. doi:10.1111/bcp.12814
Ujhelyi MR, Robert S. Pharmacokinetic aspects of digoxin-specific Fab therapy in the management of digitalis toxicity. Clin Pharmacokinet. 1995;28(6):483-493. doi:10.2165/00003088-199528060-00006
Wei, S., Niu, M.T. & Dores, G.M. Adverse Events Associated with Use of Digoxin Immune Fab Reported to the US Food and Drug Administration Adverse Event Reporting System, 1986–2019. Drugs – Real World Outcomes 8, 253–262 (2021). https://doi.org/10.1007/s40801-021-00242-x
Ward SB, Sjostrom L, Ujhelyi MR. Comparison of the pharmacokinetics and in vivo bioaffinity of DigiTAb versus Digibind. Ther Drug Monit. 2000 Oct;22(5):599-607. doi: 10.1097/00007691-200010000-00016. PMID: 11034267.

Pharmacology

Overview of Evidence

Conclusions

References

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