Before starting

Required

• Baseline
  • Serum calcium
  • Serum creatinine (for creatinine clearance)
  • Serum magnesium
  • Serum potassium
  • Thyroid function tests · digoxin may require dose amendment in thyroid disease
  • Urea and electrolytes

Ongoing once stable

Required

• Annually
  • Serum calcium
  • Serum creatinine (for creatinine clearance)
  • Serum magnesium · increased frequency may be required if long-term PPI, other medicine pre-disposing to hypomagnesaemia, or low calcium level
  • Serum potassium
  • Urea and electrolytes

Increase frequency in elderly or renal impairment

More frequent monitoring may be required in elderly people and people with renal impairment.

Consider

• Periodically in specific circumstances
  • Serum digoxin concentration · taken no less than 6 hours (ideally 8-12 hours) after last dose

When to take a digoxin level

Routine monitoring of serum digoxin is not recommended.

Consider checking serum digoxin levels in circumstances where toxicity is suspected or the digoxin level may be altered. These include:

• patient experiencing adverse effects suggestive of toxicity (such as confusion, nausea, anorexia, or disturbance of colour vision)
• concomitant use of interacting medicines (for example amiodarone, diltiazem, or verapamil)
• deteriorating renal function
• thyroid disease
• advancing age
• suspected poor adherence
• change in digoxin dose (monitor serum digoxin levels 7 days after the last dose change, in patients with normal renal function)

Abnormal results

Digoxin toxicity

Normal and abnormal serum digoxin concentrations

The therapeutic range for serum digoxin concentration is between 0.7 nanograms/mL and 2.0 nanograms/mL. The concentration can thus determine the likelihood of toxicity; in particular:

• Levels less than 1.5 nanograms/mL in the absence of hypokalaemia indicate that digoxin toxicity is unlikely.
• Levels between 1.5 nanograms/mL and 3.0 nanograms/mL, digoxin toxicity should be considered a possibility.
• Levels greater than 3.0 nanograms/mL indicate that digoxin toxicity is likely.

Be mindful of clinical signs of toxicity

However, digoxin toxicity can also occur when the serum digoxin concentration is within the therapeutic range. Therefore always interpret results in the clinical context. The presence of the following toxic symptoms may prompt an urgent measurement:

• nausea and vomiting
• visual disturbance (yellow-green discolouration)
• severe dysrhythmias

Managing toxicity

If toxicity occurs, digoxin should be withdrawn. Serious manifestations require urgent specialist management. Digoxin-specific antibody fragments are available for reversal of life-threatening overdosage.

Electrolyte imbalances

Hypokalaemia, hypomagnesaemia, and hypercalcaemia predispose the patient to digoxin toxicity, and hypokalaemia and hypomagnesaemia should be corrected either orally or intravenously, as appropriate.

Hypocalcaemia may indicate that magnesium levels are also low.

Thyroid function

Initial and maintenance doses of digoxin should be amended when thyroid function is abnormal.

Hypothyroidism

Hypothyroidism may require a reduction is digoxin dose.

Hyperthyroidism

Hyperthyoidism can lead to relative digoxin resistance, and the dose may have to be increased.

Treatment of thyrotoxicosis

During treatment of thyrotoxicosis, dosage should be reduced as the thyrotoxicosis comes under control.

Bibliography

• Smellie WS, Coleman JJ. Pitfalls of testing and summary of guidance on safety monitoring with amiodarone and digoxin. BMJ. 2007 Feb 10;334(7588):312-5
• Aspen Pharma Trading Limited. Summary of Product Characteristics – Digoxin 0.25 mg Tablets. Last revised 04/2022 [cited 09/10/2023]
• Smellie WS, Forth J, Sundar S, et al. Best practice in primary care pathology: review 4. J Clin Pathol. 2006 Sep;59(9):893-902
• National Institute for Health and Care Excellence (NICE). Chronic heart failure in adults: diagnosis and management [NG106]. Sep 2018 [cited October 2023]
• Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press, accessed via Medicines Complete [cited 09/10/2023]
• Aronson JK, Hardman M. ABC of monitoring drug therapy. Digoxin. BMJ 1992, 305: 1149-52
• NICE Clinical Knowledge Summaries (CKS). Atrial fibrillation, digoxin guideline. Updated Mar 2023 [cited 09/10/2023]
• Medicines and Healthcare products Regulatory Agency. Proton pump inhibitors in long-term use: reports of hypomagnesaemia. Drug Safety Update April 2012, vol 5 issue 9: A1. [cited 09/10/2023]
• Giardina E G, Sylvia L. UpToDate. Treatment with digoxin: Initial dosing, monitoring, and dose modification. Last updated Aug 2023. [cited 09/10/2023]
• Patel K, Wright P. Digoxin monitoring and toxicity management. The Pharmaceutical Journal. 2023 Jan;310:7969

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