PassFinals
Pharmacology & Therapeutics

Digoxin Toxicity

Digoxin inhibits the myocardial sodium-potassium pump, so in excess it both blocks conduction and provokes ectopic firing, giving bradycardia, heart block and ventricular arrhythmia.

In a nutshell

Digoxin toxicity is cardiac glycoside excess causing bradycardia, atrioventricular (AV) block and ventricular arrhythmia alongside gastrointestinal, visual and neurological symptoms, and it occurs at concentrations inside the therapeutic range. Stop digoxin, treat symptomatic bradycardia with atropine 500 micrograms intravenously, and give digoxin-specific antibody fragments for ventricular arrhythmia, high-degree block, potassium above 6.5 mmol/L or hypotension.

Classic presentation

An 82-year-old taking digoxin, furosemide and spironolactone presents with vomiting, yellow-tinged vision and a pulse of 30 after a rise in creatinine.

Key points

  • There is no NICE guideline and no UK national guideline on digoxin toxicity. The BNF, NHS Specialist Pharmacy Service and local Digifab protocols do the practical work.
  • Therapeutic range 0.7 to 2.0 nanograms/mL. Below 1.5 without hypokalaemia toxicity is unlikely, 1.5 to 3.0 possible, above 3.0 likely, and toxicity still occurs inside the range.
  • Digoxin is not removed by dialysis: the volume of distribution is 5 to 10 L/kg and protein binding about 20%, so almost none of it is in plasma.
  • Digifab is an ovine protein and can cause anaphylaxis. Each 40 mg vial costs about 750 pounds, which is why half-neutralisation is standard rather than full.
  • The BNF halves the digoxin dose with amiodarone, dronedarone or quinine. Diuretics act indirectly, by causing the hypokalaemia that potentiates digoxin.
  • The Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) flags long-term digoxin above 125 micrograms daily when the estimated glomerular filtration rate (eGFR) is under 30 mL/minute/1.73 m2.
  • Calcium in digoxin-toxic hyperkalaemia is contested. No current UK source contraindicates it; UK trust guidance treats it as a caution and gives it more slowly.
  • Most cases are chronic accumulation in an older patient whose kidney function has slipped, not deliberate overdose, which is why they are missed.

First-line investigation

12-lead ECG with continuous monitoring, plus urea and electrolytes, magnesium, calcium, renal function and a digoxin level taken at least 6 hours after the last dose.

Management

Stop the drug, read the ECG, treat the bradycardia

  • Withhold all digoxin. ABCDE, continuous cardiac monitoring, 12-lead ECG, intravenous access. Phone the National Poisons Information Service (NPIS) on 0344 892 0111.1,7
  • Send urea and electrolytes, magnesium, calcium, renal function and a digoxin level at least 6 hours after the last dose, ideally 8 to 12.3,1
  • Symptomatic bradycardia: atropine 500 micrograms IV, repeated every 3 to 5 minutes to a maximum total of 3 mg.11
  • Do not give atropine in high-degree atrioventricular block with a broad QRS. It is ineffective and can worsen the block.11

Interpret the level, correct the electrolytes

  • Therapeutic range 0.7 to 2.0 nanograms/mL. Below 1.5 without hypokalaemia toxicity is unlikely; 1.5 to 3.0 possible; above 3.0 likely.3
  • Reverse tick ST depression is digoxin effect at therapeutic levels. Toxicity shows as bradycardia, all degrees of block and ventricular arrhythmia.2,5
  • Correct hypokalaemia with ready-mixed potassium chloride: maximum 20 mmol/hour, and not above 40 mmol/L peripherally.9,3
  • Hypomagnesaemia with arrhythmia: magnesium sulfate 2 g IV over 10 to 15 minutes, repeated once if necessary.10

Digoxin-specific antibody fragments

  • Indications: ventricular tachycardia, ventricular fibrillation, asystole, symptomatic high-degree atrioventricular block, potassium above 6.5 mmol/L, or hypotension with end-organ dysfunction.2,4
  • Full neutralisation, in 40 mg vials: mg ingested multiplied by 1.6, or level in micrograms/L multiplied by weight in kg then divided by 100. Round up.12
  • Give half the calculated dose first; the rest if there is no response within 2 hours, or if toxicity recurs. Unknown amount: three to five vials.12,2
  • Reconstitute each 40 mg vial with 4 mL water for injections, dilute in sodium chloride 0.9%, infuse over 30 minutes.4,12
  • Do not use the United States multiplier of 2 with a UK protocol. UK full neutralisation uses 1.6; half neutralisation uses 0.8.2,12

Hyperkalaemia, calcium and what to avoid

  • The antidote is the potassium-lowering treatment: restoring the pump drops the potassium. Insulin-glucose can overshoot into hypokalaemia and worsen the toxicity.2,13
  • Calcium is contested, not contraindicated. UK Kidney Association 2023 says nothing about digoxin; its dose is calcium gluconate 10% 30 mL IV over 10 minutes.13
  • Royal Cornwall V7.0 says consider digoxin toxicity first. Bristol and Weston v5.2 gives calcium over 30 minutes in 100 mL glucose 5%. Neither is national guidance.6,14
  • Avoid DC cardioversion unless there is no alternative. Transvenous pacing can precipitate asystole or ventricular fibrillation. Isoprenaline is hard to titrate safely.2

After the antidote

  • Continuous ECG for at least 24 hours, with regular temperature, blood pressure and potassium. Improvement usually starts within 30 minutes.12
  • Complexes dissociate from about 12 hours and Fab's half-life is about 20 hours, so toxicity can recur. Repeat doses follow clinical features.2
  • Do not measure a digoxin level after Digifab: it interferes with the assay, so the result adds nothing.12
  • Renal impairment delays clearance of the complex and free digoxin can reappear days later, so observe longer and recheck renal function.12
  • Before restarting digoxin, reassess the indication, dose, renal function, electrolytes, interactions and who will monitor the level.3,1

Exam traps

  • Reverse tick is digoxin effect, not toxicity. Its presence proves the patient takes digoxin and nothing more.
  • A therapeutic concentration does not exclude toxicity, and a level drawn under 6 hours after a dose is uninterpretably high.
  • In chronic toxicity potassium is low and that worsens it. In acute overdose potassium is high and that measures the severity.
  • Do not give a UK Digifab formula an American multiplier. The UK uses 1.6 for full neutralisation, the United States 2, and they are not interchangeable.
  • Do not measure a digoxin level after antibody fragments. Fab interferes with the assay, so the number is meaningless.
  • Do not DC cardiovert digoxin-toxic ventricular tachycardia if there is any alternative; mortality is significant even at low energy.
  • Atropine is useless and may be harmful in high-degree AV block with a broad QRS. That patient needs the antidote.
  • Insulin-glucose for digoxin-toxic hyperkalaemia can overshoot into hypokalaemia and worsen the toxicity. The antibody fragments lower the potassium themselves.

Illustrations

Na/K-ATPase mechanism and potassium competitionDiagram of the myocyte Na/K-ATPase pump showing digoxin and potassium competing for the same binding site on the alpha subunit, and downstream effects on the Na/Ca exchanger.PassFinals · original
Digoxin-specific antibody fragment mechanismDiagram illustrating how digoxin-specific antibody fragments (DigiFab) bind circulating digoxin with greater affinity than the Na/K-ATPase pump and draw it out of the tissue compartment.PassFinals · original

Key sources

  1. BNF, Digoxin (Drug action, indications and dose, the cautions list (hypercalcaemia, hypokalaemia, hypomagnesaemia and hypoxia, each carrying a risk of digitalis toxicity), the STOPP criteria, the instruction to halve the dose with amiodarone, dronedarone and quinine, and the rule that blood for plasma-digoxin assay is taken at least 6 hours after a dose. Text taken from reports/textbook-source-packs/batch06/digoxin.md, fetched live 2026-08-07; bnf.nice.org.uk returns an empty body to automated fetching.)
  2. Andrews PJ, Thompson H. Digoxin: monitoring, limitations of its use, and managing toxicity. British Journal of Cardiology 2024;31(suppl 3):S19-S23 (doi 10.5837/bjc.2024.s10. Source of the reverse-tick correction, the atropine, pacing, cardioversion and isoprenaline cautions, the half-neutralisation formulae, the volume of distribution and protein binding that explain why dialysis fails, the assay ceiling, the Box 1 indications reproduced from the 2023 European consensus, and the mortality figures. Declared conflict: the supplement was solely funded by a grant from BTG Pharmaceuticals (a SERB company), the DigiFab manufacturer, and both authors received an honorarium.)Published 1 Aug 2024
  3. NHS Specialist Pharmacy Service, Digoxin monitoring (The therapeutic range of 0.7 to 2.0 nanograms/mL, the three toxicity-likelihood bands, sampling no less than 6 hours and ideally 8 to 12 hours after the last dose, the 7-day interval after a dose change in normal renal function, and the baseline and annual monitoring panel. The page states it was last updated 27 December 2023.)Updated 27 Dec 2023
  4. BNF, Digoxin-specific antibody fragments (The licensed indication wording and the administration instructions: reconstitute with water for injections 4 mL per vial, dilute in sodium chloride 0.9%, give over 30 minutes. The monograph deliberately gives no dose, directing that serious cases are discussed with the National Poisons Information Service and the product literature consulted. Text from reports/textbook-source-packs/batch06/digoxin-specific-antibody-fragments.md, fetched live 2026-08-07.)
  5. Royal College of Emergency Medicine and National Poisons Information Service, Management of Patients with Suspected but Unidentified Poisoning in the Emergency Department (April 2025. Table 4 on page 9 gives, for digoxin and other cardiac glycosides: ST 'sagging' with QRS prolongation, T wave inversion, shortened QT with PR prolongation, deteriorating to bradycardia and ventricular arrhythmias, with atropine as initial management.)Published 1 Apr 2025
  6. Royal Cornwall Hospitals NHS Trust, Adult Hyperkalaemia Management Clinical Guideline V7.0 (Approved December 2025, valid to December 2028, written in accordance with UK Kidney Association 2023. Section 2.1 gives the severity bands, severe being 6.5 mmol/L or more. Section 2.6.1 carries the digoxin caution verbatim: calcium gluconate can increase the effects of oral digoxin, digoxin toxicity can result in hyperkalaemia, and use of calcium gluconate as a cardiac stabiliser can enhance this process, so consider digoxin toxicity prior to administration. A single-trust guideline, not national guidance.)Published 1 Dec 2025
  7. TOXBASE and the UK National Poisons Information Service (NPIS) (The primary UK clinical toxicology database. Its public page states that TOXBASE is for registered health professionals only and gives the UK NPIS telephone number 0344 892 0111. The database itself sits behind a login and was not consulted for this chapter; nothing here rests on it except the contact route.)
  8. National Poisons Information Service, TOXBASE (The publicly readable NPIS description of TOXBASE: over 21,000 monographs, coordinated by the NPIS Edinburgh Unit, commissioned by the UK Health Security Agency, free to UK NHS units, and explicitly not available for public access. Descriptive only; it carries no clinical content and supports no number in this chapter.)
  9. BNF, Potassium chloride (Directions for administration: ready-mixed infusion solutions should be used where possible, the maximum infusion rate is 20 mmol/hour, and for peripheral infusion the concentration should not usually exceed 40 mmol/L. Contra-indicated at a plasma-potassium concentration above 5 mmol/L. Text from reports/textbook-source-packs/batch06/potassium-chloride.md, fetched live 2026-08-07.)
  10. BNF, Magnesium sulfate (Emergency treatment of serious arrhythmias, adult: 2 g by intravenous injection over 10 to 15 minutes, dose may be repeated once if necessary. Text from reports/textbook-source-packs/batch04/magnesium-sulfate.md, fetched live 2026-08-07.)
  11. Resuscitation Council UK, Adult advanced life support Guidelines (2025 guidelines, bradycardia section: if bradycardia is accompanied by adverse signs, give atropine 500 micrograms IV and, if necessary, repeat every 3 to 5 minutes to a total of 3 mg. The same section states that atropine should not be given to patients with high-degree atrioventricular block and wide QRS, because it is ineffective and may worsen the block.)
  12. Gloucestershire Hospitals NHS Foundation Trust, Guidance for Managing Digoxin Overdose with Digifab (The four-path acute, acute-on-chronic, chronic and under-20 kg algorithm, both full-neutralisation formulae, the half-dose-first rule, reconstitution and infusion, continuous ECG monitoring for at least 24 hours, and the statement that Digifab interferes with serum digoxin monitoring so there is no clinical benefit in measuring it afterwards. The PDF footer reads approved by the Drug and Therapeutics Committee October 2015, updated May 2020, review date May 2023: a single-trust protocol past its review date.)Updated 1 May 2020
  13. UK Kidney Association, Clinical Practice Guideline: Treatment of Acute Hyperkalaemia in Adults (Final version October 2023, published 19 December 2023. Guideline 16.2a: calcium gluconate 10% 30 mL over 10 minutes, or calcium chloride 10% 10 mL over 5 minutes. Guidelines 16.3.1 and 16.3.2: 10 units soluble insulin in 25 g glucose. The word digoxin appears exactly once in the whole document, in an appendix list of causes of hyperkalaemia, and there is no digoxin caveat attached to the calcium recommendation.)Published 19 Dec 2023
  14. University Hospitals Bristol and Weston NHS Foundation Trust, Management of Acute Hyperkalaemia in Adults v5.2 (Page 6: if also taking digoxin, administer calcium over 30 minutes in 100 mL 5% dextrose to prevent myocardial digoxin toxicity, and seek senior opinion about digoxin antibody fragments. Page 8: the hypokalaemic response to salbutamol is attenuated in patients taking digoxin. The cited authority for the digoxin line is the GAIN (Northern Ireland) 2014 guideline, and the document's own review date of 1 December 2023 has passed, so it corroborates practice rather than carrying current authority.)Updated 5 Sept 2023

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.