Does Dronedarone (Multaq) increase digoxin (Digitalis) toxicity?

From the Guidelines

Dronedarone significantly increases the risk of digoxin toxicity and the combination should be avoided whenever possible. If both medications must be used together, the digoxin dose should be reduced by at least 50% and serum digoxin levels should be closely monitored, aiming for the lower end of the therapeutic range 1. Dronedarone inhibits P-glycoprotein, a transport protein responsible for digoxin elimination, resulting in increased digoxin serum concentrations by approximately 2.5-fold. This interaction can lead to serious adverse effects including nausea, vomiting, visual disturbances, confusion, and potentially life-threatening cardiac arrhythmias. Some key points to consider when using dronedarone and digoxin together include:

• Monitoring serum digoxin levels closely to avoid toxicity 1
• Reducing the digoxin dose by at least 50% when initiating dronedarone therapy 1
• Educating patients about the signs of digoxin toxicity and instructing them to seek immediate medical attention if symptoms develop
• Considering alternative antiarrhythmic medications that have less significant interactions with digoxin, such as amiodarone (though it also interacts with digoxin but is sometimes necessary) 1. It is also important to note that the use of dronedarone in patients with heart failure, particularly those with NYHA class III or IV, may be associated with increased risk of adverse events, including sudden mortality when used with concomitant digoxin therapy 1.

From the FDA Drug Label

Dronedarone increased digoxin exposure by 2.5-fold by inhibiting the P-gP transporter [see Drug Interactions (7. 1)]. Dronedarone can increase digoxin toxicity due to increased exposure.

• If digoxin treatment is continued, halve the dose of digoxin,
• Monitor serum levels closely,
• Observe for toxicity 2.

From the Research

Dronedarone and Digoxin Toxicity

• Dronedarone may increase digoxin plasma levels through inhibition of P-glycoprotein, potentially leading to digoxin toxicity 3, 4, 5, 6.
• Studies have shown that concomitant use of dronedarone and digoxin can increase the risk of digitalis intoxication, although the evidence is not always consistent 3, 5.
• A case report described a patient who presented with chronic symptoms attributable to dronedarone-induced digoxin toxicity, highlighting the importance of monitoring digoxin plasma levels when using these medications together 4.
• The PALLAS trial found that dronedarone was associated with increased cardiovascular death and heart failure in patients with permanent atrial fibrillation, and that the risk was higher in patients taking digoxin 5.
• It is recommended to closely monitor plasma digoxin levels or administer a lower loading dose of digoxin in patients taking dronedarone concomitantly to minimize the risk of toxicity 4, 6.

Mechanism of Interaction

• Dronedarone inhibits P-glycoprotein-mediated digoxin clearance, leading to increased steady-state digoxin levels 4, 5, 6.
• This interaction can increase the risk of digoxin toxicity, particularly in patients with renal impairment or those taking other medications that interact with digoxin 4, 5, 6.

Clinical Implications

• Healthcare providers should be aware of the potential interaction between dronedarone and digoxin and take steps to minimize the risk of toxicity, such as monitoring digoxin plasma levels and adjusting the dose as needed 4, 5, 6.
• Patients taking concomitant dronedarone and digoxin should be closely monitored for signs and symptoms of digoxin toxicity, including nausea, diarrhea, weakness, and arrhythmias 4, 5, 6.