Published: 2 March 2023

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Digoxin toxicity – don't break my heart

Published: 2 March 2023
Prescriber Update 44(1): 11–13
March 2023

The Centre for Adverse Reactions Monitoring (CARM) recently received a report of digoxin toxicity, where the patient experienced renal failure, hyperkalaemia, bradycardia and cardiac failure (CARM ID: 144388). Although this patient experienced severe cardiac problems, the clinical features of digoxin toxicity can be non-specific and are discussed further in this article.

Digoxin therapy

Digoxin is a cardiac glycoside that increases the force of myocardial contraction and reduces conductivity within the atrioventricular node of the heart. It is used in the management of systolic heart failure and certain supraventricular arrhythmias, particularly atrial flutter and fibrillation.¹

The dose of digoxin should be tailored on an individual basis. Factors to consider include:

• indication for digoxin therapy¹
• patient age¹
• lean body weight¹
• renal function.¹

Digoxin is initiated via a rapid or slow loading dose, followed by a maintenance dose that ranges from 62.5 mcg to 250 mcg per day in adults and children over 10 years of age.^1,2 In order to reduce the risk of medication errors, it is important that healthcare professionals counsel patients about dose changes.

Digoxin toxicity

Digoxin has a narrow therapeutic index, and toxicity is a well-recognised clinical problem associated with significant morbidity and mortality. Toxicity can occur following an acute overdose and in patients on long-term therapy.³

The clinical features of toxicity are often non-specific, and patients can present with visual disturbances and cardiac (dysrhythmia), gastrointestinal (nausea, vomiting, abdominal pain) and neurological (confusion, weakness, delirium) symptoms.³

Serum digoxin levels can be used to assist diagnosis, but they do not correlate consistently with the clinical manifestations of toxicity.³ Patients are at an increased risk of digoxin toxicity when serum digoxin levels rise above 2.6 nmol/L (2 ng/mL).^3,4 However, toxicity can also occur when serum levels are within the therapeutic range, especially in the presence of certain electrolyte disturbances (eg, hypokalaemia).^3,4

There are several risk factors for digoxin toxicity, and serum digoxin levels should be interpreted in conjunction with other clinical markers, such as serum potassium levels and renal and thyroid function tests.⁵

Risk factors for digoxin toxicity (list not exhaustive)

• Renal impairment: digoxin is eliminated in the urine; the half-life of digoxin is prolonged in patients with kidney disease.²
• Concomitant medicines: there are a number of important drug interactions with digoxin, including inducers/inhibitors of P-glycoprotein and medicines associated with electrolyte abnormalities (eg, diuretics).²
• Age: the incidence of digoxin toxicity increases with age.⁶
• Comorbidities: an increase in the number of comorbid conditions, including amyloidosis, thyroid disease and cardiovascular disease, may increase patient susceptibility to digoxin toxicity.⁶
• Electrolyte imbalances: several electrolyte abnormalities, including hypokalaemia, hypomagnesemia and hypercalcemia, increase patient susceptibility to the toxic effects of digoxin.³
• Acute illnesses that may cause dehydration or acute renal insufficiency.³

Management of toxicity includes standard supportive care, correction of electrolyte imbalances, activated charcoal, atropine for acute bradyarrhythmias, and administration of an antidote.^1,7

Contact the National Poisons Centre and/or access TOXINZ for advice on the management of digoxin overdose.

CARM reports

Between January 2008 to December 2022, CARM received 88 case reports with symptoms suggestive of digoxin toxicity, including 5 where drug toxicity was reported as an adverse reaction (CARM ID numbers: 81719, 111281, 113571, 141350, 144388).

Conclusion

Due to digoxin’s narrow therapeutic index, healthcare professionals should remain vigilant about the possibility of digoxin toxicity and consider dose adjustments in patients predisposed to toxicity. Given the potential for harm and the non-specific symptoms of toxicity, remind patients taking digoxin to seek medical attention if they feel unwell.

References

1. Pharmacy Retailing Limited. 2019. Lanoxin Data Sheet November 2019. URL: medsafe.govt.nz/profs/datasheet/l/Lanoxintabelixinj.pdf (accessed 19 December 2022).
2. Giardina E-G. 2022. Treatment with digoxin: initial dosing, monitoring, and dose modification. In: UpToDate 16 August 2022. URL: uptodate.com/contents/treatment-with-digoxin-initial-dosing-monitoring-and-dose-modification (accessed 19 December 2022).
3. Levine MD and O’Connor A. 2022. Digitalis (cardiac glycoside) poisoning. In: UpToDate 9 June 2022. URL: uptodate.com/contents/digitalis-cardiac-glycoside-poisoning (accessed 19 December 2022).
4. Goldberger A. 2022. Cardiac arrhythmias due to digoxin toxicity. In: UpToDate 20 October 2022. URL: uptodate.com/contents/cardiac-arrhythmias-due-to-digoxin-toxicity (accessed 19 December 2022).
5. New Zealand Formulary (NZF). 2023. NZF v127: Digoxin 1 January 2023. URL: nzf.org.nz/nzf_982 (accessed 18 January 2023).
6. Wofford JL and Ettinger WH. 1991. Risk factors and manifestations of digoxin toxicity in the elderly. American Journal of Emergency Medicine 9(2 Suppl 1): 11-5; discussion 33-4. DOI: 10.1016/0735-6757(91)90161-c (accessed 20 December 2022).
7. Pincus M. 2016. Management of digoxin toxicity. Australian Prescriber 39(1): 18-20. DOI: 10.18773/austprescr.2016.006 (accessed 19 December 2022).