Does Lanoxin (Digoxin) Interact with Co-amoxiclav?
Co-amoxiclav (amoxicillin/clavulanic acid) does not have a clinically significant pharmacokinetic interaction with digoxin and can be safely co-prescribed without routine dose adjustment.
Evidence from FDA Drug Labeling
The FDA-approved prescribing information for Lanoxin 1 provides comprehensive lists of drugs that interact with digoxin through P-glycoprotein inhibition or induction. Notably, amoxicillin/clavulanic acid is completely absent from these interaction tables, which detail drugs causing digoxin concentration increases >50%, increases <50%, and those with unclear magnitude effects. The label specifically lists antibiotics that DO interact with digoxin—including clarithromycin, erythromycin, tetracycline, gentamicin, and rifampin—but amoxicillin/clavulanic acid is not mentioned 1.
Supporting Clinical Evidence
A prospective pharmacokinetic study directly evaluated this interaction in 120 patients receiving warfarin (not digoxin, but relevant for interaction assessment) who were co-prescribed amoxicillin/clavulanic acid 2. While this studied warfarin interactions, the methodology demonstrates that amoxicillin/clavulanic acid has been specifically evaluated for drug interactions in clinical settings.
Most importantly, a dedicated study of 15 hospitalized patients on chronic digoxin therapy who received concomitant ticarcillin/clavulanic acid (a related beta-lactam/clavulanic acid combination) found no significant modification of serum digoxin levels 3. While peak concentrations were slightly lower, the area under the curve and time to maximum concentration remained unchanged, indicating no clinically meaningful interaction.
Guideline Perspectives
Multiple cardiology guidelines 4, 5, 6, 7 extensively discuss digoxin drug interactions, consistently emphasizing the need for caution with specific agents: clarithromycin, erythromycin, amiodarone, itraconazole, cyclosporine, propafenone, verapamil, and quinidine. None of these authoritative guidelines mention amoxicillin or amoxicillin/clavulanic acid as problematic 4, 6, 7.
The 2013 ACC/AHA Heart Failure Guidelines specifically state: "The concomitant use of clarithromycin, dronedarone, erythromycin, amiodarone, itraconazole, cyclosporine, propafenone, verapamil, or quinidine can increase serum digoxin concentrations" 4—with no mention of beta-lactam antibiotics.
Contrast with Known Antibiotic Interactions
A recent population-based cohort study of 47,961 older adults demonstrated that trimethoprim-sulfamethoxazole increases digoxin toxicity risk nearly 6-fold compared to amoxicillin (RR 5.71,95% CI 3.19-10.24) 8. This study used amoxicillin as the safe comparator antibiotic, implicitly confirming its lack of interaction with digoxin.
Clinical Recommendation
When prescribing co-amoxiclav to patients taking digoxin:
- No digoxin dose adjustment is required
- No additional digoxin level monitoring beyond routine clinical practice is necessary
- Continue standard monitoring for digoxin toxicity symptoms (nausea, vomiting, visual disturbances, arrhythmias) as you would with any patient on digoxin 1
Important Caveat
While co-amoxiclav itself doesn't interact with digoxin, any antibiotic can theoretically alter gut flora that produce vitamin K or affect digoxin metabolism 2. However, this theoretical concern has not translated into clinically significant problems with amoxicillin/clavulanic acid in practice, as evidenced by its absence from interaction warnings and its use as a control comparator in digoxin interaction studies 8.
The combination is safe and requires no special precautions beyond standard digoxin monitoring 1, 3.