Toxicology & Substance Use · Topic 8 of 17

Digoxin Toxicity

Toxicology · cardiac glycosides

Digoxin Toxicity

Dangerous rhythms or rising potassium on digoxin call for digoxin immune Fab — in acute overdose, a potassium above 5.0 is a red flag.

Key numbers

Acute overdose: potassium above 5.0 is ominousK⁺ > 5.0 mEq/L

Fab vials = level × weight ÷ 100ng/mL × kg ÷ 100

01 · GiveGive digoxin immune Fab (DigiFab)

Digoxin immune Fab (40-mg vials, each binding about 0.5 mg digoxin) is the antidote for life-threatening or potentially life-threatening toxicity and lowers the risk of death.

02 · The numberAcute overdose: potassium above 5.0 is ominous

In acute overdose, hyperkalemia tracks severity: before Fab, mortality was about 50% with K⁺ 5.0–5.5 and near 100% above 5.5 mEq/L, so K⁺ > 5.0 is a classic Fab indication.

03 · Look forBidirectional VT points to digoxin toxicity

Serious digoxin-toxic rhythms include bidirectional ventricular tachycardia, nonparoxysmal junctional tachycardia in atrial fibrillation, VF and complete heart block; hyperkalemia is a serious sign.

Causes & risk factors

Why it happens

Chronic toxicity: older age and kidney declineMost toxicity is chronic, in older patients with worsening renal function, dehydration, hypokalemia, hypomagnesemia or hypercalcemia, or interacting drugs (amiodarone, calcium channel blockers, macrolides, NSAIDs, diuretics).

Presentation

What you'll see

Nausea, confusion and visual halosNoncardiac clues are nonspecific: anorexia, nausea, vomiting, diarrhea, headache, confusion and lethargy, plus blurred vision, halos and altered color perception.

Diagnosis & monitoring

Work-up

Life-threatening signs that demand Fab must knowLife-threatening digoxin toxicity: ventricular tachycardia or fibrillation, asystole, symptomatic high-degree AV block or atropine-resistant bradycardia, severe hyperkalemia, or hypotension with end-organ dysfunction — each warrants digoxin immune Fab.

Fab vials = level × weight ÷ 100Dose Fab from a steady-state level: vials = serum digoxin (ng/mL) × weight (kg) ÷ 100; from a known ingestion: vials = mg ingested ÷ 0.5. Round up.

Draw the level 6–8 hours after a doseDraw the digoxin level at least 6–8 hours after the last dose (serum–tissue equilibration); levels correlate poorly with toxicity, which can occur within the therapeutic range of 0.8–2.0 ng/mL.

Potassium can drop fast after FabAfter Fab, potassium shifts back into cells and can fall quickly — check it often in the first hours; heart failure and AF rate may worsen as digoxin's effect is lost.

Empiric Fab: 10 vials acute, 6 chronicWithout a level or ingested amount: acute ingestion — 10 vials, then 10 more if needed (20 total); chronic toxicity — 6 vials in adults.

Do right now

In this order

First moves

Life-threatening signs that demand Fab

→

Acute overdose: potassium above 5.0 is ominousK⁺ > 5.0 mEq/L

→

Give digoxin immune Fab (DigiFab)

→

Potassium can drop fast after Fab

Why each step

Life-threatening signs that demand FabLife-threatening digoxin toxicity: ventricular tachycardia or fibrillation, asystole, symptomatic high-degree AV block or atropine-resistant bradycardia, severe hyperkalemia, or hypotension with end-organ dysfunction — each warrants digoxin immune Fab.

Acute overdose: potassium above 5.0 is ominousIn acute overdose, hyperkalemia tracks severity: before Fab, mortality was about 50% with K⁺ 5.0–5.5 and near 100% above 5.5 mEq/L, so K⁺ > 5.0 is a classic Fab indication.

Give digoxin immune Fab (DigiFab)Digoxin immune Fab (40-mg vials, each binding about 0.5 mg digoxin) is the antidote for life-threatening or potentially life-threatening toxicity and lowers the risk of death.

Management

Orders

Mild chronic toxicity: hold digoxin, fix electrolytesMild chronic toxicity without ECG changes or arrhythmia: stop or reduce digoxin, correct hypokalemia and hypomagnesemia carefully, and monitor on telemetry.

The rules

Know these

Digoxin levels are invalid after FabAfter Fab, standard digoxin immunoassays give clinically misleading results; follow the ECG, potassium and the clinical picture instead.

Dialysis does not remove digoxinDigoxin's large volume of distribution and tissue binding make hemodialysis and hemoperfusion ineffective; activated charcoal may be considered within 2 hours of an acute ingestion.

Acute overdose or chronic toxicity?

Commonly confused

Typical patient	Intentional or accidental large ingestion
Potassium	Hyperkalemia marks severity
Digoxin level	High
Empiric Fab dose (level unknown)	10 vials, then 10 more if needed

Commonly confused

Tell apart

IV calcium: not proven harmful, not helpfulCalcium was historically contraindicated in digoxin toxicity ("stone heart"); human data show no clear harm, but it has no proven benefit for digoxin-induced hyperkalemia — treat that with Fab.

More detail

Reference

Show 5 reference facts

Label indications also include an adult ingestion of ≥ 10 mg (child ≥ 4 mg), an expected level ≥ 10 ng/mL, or a chronic steady-state level > 6 ng/mL.

Infuse Fab over at least 30 minutes; give it as a bolus if cardiac arrest is imminent, accepting more infusion reactions.

Ovine Fab can provoke hypersensitivity, especially in patients allergic to papain, chymopapain, papaya extracts or bromelain.

Atropine and temporary pacing may bridge bradycardia, but pacing in digoxin toxicity should be done only by expert teams; Fab remains the definitive therapy.

Until Fab is available, lidocaine, phenytoin or magnesium may be tried for ventricular dysrhythmias; avoid epinephrine and isoproterenol for bradycardia because they can trigger ventricular fibrillation.

Pearl

In acute digoxin overdose the potassium is the prognosis: hyperkalemia means the sodium–potassium pump is poisoned — give Fab.

Sources · DigiFab (digoxin immune fab, ovine) prescribing information — DailyMed · Andrews P et al. Diagnosis and practical management of digoxin toxicity: a narrative review and consensus. Eur J Emerg Med 2023;30:395–401 · Hack JB et al. Expert consensus on the diagnosis and management of digoxin toxicity. Am J Med 2025;138:25–33 (abstract confirmed via Europe PMC) · Merck Manual Professional — Medications for Heart Failure (digoxin) · Zand F, Asadi S, Katibeh P. Good outcome after digoxin toxicity despite very high serum potassium level. Iran Red Crescent Med J 2011;13:680–681 (cites pre-Fab K⁺–mortality data) · Hyperkalemia management in the emergency department: an expert panel consensus. J Am Coll Emerg Physicians Open 2021;2:e12572 · Merck Manual Professional — General Principles of Poisoning · Lavonas EJ et al. 2023 AHA focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning. Circulation 2023;148:e149–e184 · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).