Is it okay to give flecainide with digoxin?

Flecainide and Digoxin Coadministration

Yes, flecainide can be given with digoxin, but digoxin levels must be monitored closely because flecainide increases plasma digoxin concentrations by 13-19%, requiring potential dose adjustment. 1

Drug Interaction Mechanism

• Flecainide increases plasma digoxin levels by 13-19% at six hours post-dose when administered concurrently. 2
• The FDA label specifically states that flecainide has been administered to patients receiving digitalis preparations without adverse effects, though monitoring is required. 2
• This interaction occurs because both drugs can affect cardiac conduction, and the pharmacokinetic interaction leads to elevated digoxin concentrations. 3

Monitoring Requirements

• The ACC/AHA/HRS guidelines explicitly recommend monitoring digoxin concentrations when flecainide is coadministered. 1
• Check digoxin levels more frequently when initiating flecainide therapy, targeting trough levels of 0.5-1.0 ng/mL. 4
• Monitor for signs of digoxin toxicity including gastrointestinal symptoms (anorexia, nausea, vomiting), visual changes, and cardiac arrhythmias. 1
• Watch for PR interval prolongation, which occurred in 6 of 15 subjects receiving both drugs concurrently in clinical studies. 3

Dosing Considerations

• No routine digoxin dose reduction is mandated when starting flecainide, unlike with amiodarone (which requires 30-50% reduction) or dronedarone (which requires 50% reduction). 1
• However, be prepared to reduce digoxin dose if levels rise above therapeutic range or toxicity symptoms emerge. 2
• The 13-19% increase in digoxin levels is generally well-tolerated but becomes clinically significant in patients with baseline high-normal digoxin levels or those with risk factors for toxicity. 3

Critical Precautions When Using Both Drugs

• Both drugs have AV nodal blocking properties, creating additive effects on cardiac conduction. 1
• Avoid this combination in patients with second or third-degree AV block without a pacemaker. 1
• Use extreme caution in patients with sinus node dysfunction, even with first-degree AV block. 1
• Patients with renal dysfunction require particular vigilance as both drugs are renally cleared to varying degrees. 1

Clinical Evidence Supporting Coadministration

• Multiple clinical trials have successfully used flecainide and digoxin together for atrial arrhythmias after cardiac surgery, demonstrating safety when properly monitored. 5, 6, 7
• In one randomized study of 29 post-CABG patients, flecainide alone was more effective than digoxin alone for acute atrial arrhythmias, but the combination has been used safely in clinical practice. 7
• A formal interaction study in 15 healthy subjects confirmed the 13-24% increase in digoxin levels but found this was generally well-tolerated with appropriate monitoring. 3

Common Pitfalls to Avoid

• Never assume digoxin levels will remain stable after adding flecainide—always recheck levels within 1-2 weeks. 1
• Don't overlook the additive negative effects on AV conduction, particularly in elderly patients or those with pre-existing conduction disease. 3
• Remember that hypokalemia and hypomagnesemia increase digoxin toxicity risk even at lower serum levels, so electrolytes must be optimized. 8
• Be aware that flecainide is metabolized by CYP2D6, and drugs inhibiting this enzyme (quinidine, fluoxetine) can increase flecainide levels, indirectly worsening the interaction. 9