Drug interactions with digoxin

It is very important to consider interactions when prescribing cardiac glycosides, which have a very narrow therapeutic range.

A reference such as the BNF should be used when starting any new therapy in patients on cardiac glycosides.

Important interactions include:

• antiarrhythmic, antimalarials, calcium channel blockers - many of which increase the plasma concentration of digoxin (1)
  • amiodarone - it is recommended that the dose of digoxin is reduced by half when initiating amiodarone; as the interaction is dose dependent and can be delayed, therefore levels should be checked at 1-2 weeks and at one month after initiation of amiodarone
  • diltiazem - digoxin levels may be increased by 20-85% ; therefore monitor levels
  • verapamil - digoxin levels are increased by about 40% with 160mg per day, and by 70% with 240mg per day; dose adjustment is necessary to avoid toxicity
  • hydroxychloroquine and chloroquine - a 70% increase in digoxin levels has been observed in some patients treated concurrently with these drugs; therefore monitor levels
    
    
• diuretics - prevent potassium depletion in patients taking diuretics by using a potassium-sparing diuretic and monitor the plasma potassium concentration regularly - remember that ACE inhibitors and angiotensin receptor antagonists can result in potassium retention (2)
  
  
• antibiotics - in about 10% of patients digoxin is metabolized by the gut intestinal bacteria, mainly Eubacterium glenum. The antibiotics tetracycline, erythromycin and clarithromycin inhibit this breakdown and so increase the systemic availability of digoxin (2)
  
  
• other interactions (1):
  • benzodiazepines - digoxin toxicity has been observed in some patients treated concurrently with alprazolam or diazepam; monitor levels
  • cliclosporin - marked increase in digoxin levels has been seen in some patients; monitor levels
  • itraconazole - can lead to significant increases in digoxin levels resulting in toxicity
  • NSAIDs - some studies have shown increases in digoxin levels in patients treated with ibuprofen, diclofenac and indometacin; all NSAIDs have the potential to cause renal failure and therefore could result in digoxin toxicity; therefore monitor levels
  • quinine - may result in increased digoxin levels; monitor levels
  • quinidine - digoxin levels may be doubled and therefore doses should be halved to avoid toxicity
    

Reference:

1. Prescriber (2004); 15 (8): 68-73.
2. British Heart Foundation (Factfile 7/2001). The use of digoxin.