Is it safe to prescribe levofloxacin (Levaquin) to a patient who is taking digoxin?

Levofloxacin and Digoxin Co-Prescription

Levofloxacin can be safely prescribed to patients taking digoxin without dose adjustment, as the FDA label explicitly states no significant pharmacokinetic interaction exists between these medications. 1

Evidence from FDA Drug Label

The FDA-approved levofloxacin label provides definitive guidance on this combination:

• No significant effect of levofloxacin on digoxin peak plasma concentrations, AUC, or other disposition parameters was detected in clinical studies involving healthy volunteers. 1
• Levofloxacin absorption and disposition kinetics were similar in the presence or absence of digoxin. 1
• No dosage adjustment for levofloxacin or digoxin is required when administered concomitantly. 1

This FDA guidance takes precedence over theoretical concerns, as it represents controlled clinical trial data specifically evaluating this drug combination.

Supporting Research Evidence

A placebo-controlled, randomized, double-blind crossover study in 12 healthy subjects confirmed the FDA findings:

• Levofloxacin 500 mg twice daily for 6 days had no significant effect on digoxin pharmacokinetics (Cmax, AUC, or other disposition parameters). 2
• Steady-state levofloxacin absorption and disposition were similar in the presence or absence of digoxin. 2
• An important pharmacokinetic interaction between levofloxacin and digoxin is unlikely to occur when administered concomitantly. 2

Critical Distinction from Other Fluoroquinolones

Levofloxacin differs fundamentally from ciprofloxacin in its interaction profile with digoxin:

• Ciprofloxacin has been associated with digoxin toxicity through a documented drug-drug interaction mechanism. 3
• A case report documented nausea and anorexia consistent with digoxin toxicity when ciprofloxacin was added to a patient's regimen; symptoms resolved 48 hours after discontinuing digoxin. 3
• This interaction profile does not apply to levofloxacin, which has been specifically studied and shown not to interact with digoxin. 1, 2

Practical Clinical Approach

When prescribing levofloxacin to a digoxin-treated patient:

• Proceed with standard dosing of both medications without adjustment. 1
• Routine digoxin level monitoring is not required solely because of levofloxacin co-administration. 1, 2
• Continue standard digoxin monitoring based on the patient's underlying risk factors (age >70 years, renal impairment, electrolyte abnormalities, other interacting medications). 4, 5

Important Caveat: Antidiabetic Drug Interaction

If the patient is also taking antidiabetic agents, monitor blood glucose closely, as levofloxacin can cause both hyperglycemia and hypoglycemia independent of any digoxin interaction:

• Disturbances of blood glucose have been reported in patients treated concomitantly with fluoroquinolones and antidiabetic agents. 1
• Severe hypoglycemia has been documented in elderly patients with Type 2 diabetes receiving oral hypoglycemic agents and levofloxacin. 6
• This glucose monitoring requirement is unrelated to digoxin co-administration but represents a separate safety concern with levofloxacin. 1, 6

Medications That DO Require Digoxin Dose Reduction

For context, the following medications genuinely interact with digoxin and require dose adjustment (unlike levofloxacin):

• Amiodarone, verapamil, diltiazem, clarithromycin, erythromycin, itraconazole, cyclosporine, propafenone, and quinidine require a 30–50% digoxin dose reduction. 4, 5
• Dronedarone requires at least a 50% digoxin dose reduction. 5
• Levofloxacin is not included in this list of interacting medications. 1