Is amiodarone (antiarrhythmic medication) cardiotoxic?

From the Guidelines

Amiodarone can be hard on the heart, despite being used to treat heart rhythm problems, and its use should be carefully considered due to potential side effects and complications, as noted in the 2016 ESC guidelines for the management of atrial fibrillation 1.

Potential Risks and Complications

The medication is typically prescribed for serious arrhythmias like ventricular tachycardia or atrial fibrillation when other treatments have failed. While amiodarone effectively controls abnormal heart rhythms, it can paradoxically cause heart problems including:

• Bradycardia (slow heart rate)
• Heart block
• Worsening of existing arrhythmias, such as torsades de pointes, as mentioned in the 2011 ACCF/AHA/HRS focused updates 1

Monitoring and Maintenance

The typical maintenance dose ranges from 100-400 mg daily, following a loading period. Patients taking amiodarone require regular monitoring, including:

• ECGs
• Thyroid function tests
• Liver function tests
• Pulmonary function tests, as recommended in the 2006 ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation 1

Mechanism of Action and Side Effects

The medication works by blocking potassium channels in heart cells, which prolongs the heart's action potential and refractory period, but this same mechanism can lead to QT interval prolongation and potential complications. Amiodarone has an extremely long half-life (up to 100 days), meaning side effects may persist for weeks or months after stopping the medication, as noted in the 2001 ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation 1.

Key Considerations

When considering the use of amiodarone, it is essential to weigh the potential benefits against the risks, particularly in patients with underlying heart conditions or those taking other medications that may interact with amiodarone, as highlighted in the 2011 ACCF/AHA/HRS focused updates 1 and the 2006 ACC/AHA/ESC guidelines 1.

From the FDA Drug Label

While only a limited number of in vivo drug-drug interactions with amiodarone have been reported, chiefly with the oral formulation, the potential for other interactions should be anticipated. In patients receiving digoxin therapy, administration of oral amiodarone regularly results in an increase in serum digoxin concentration that may reach toxic levels with resultant clinical toxicity Amiodarone taken concomitantly with digoxin increases the serum digoxin concentration by 70% after one day. Antihypertensives: Amiodarone should be used with caution in patients receiving ß- receptor blocking agents (e.g., propranolol, a CYP3A4 inhibitor) or calcium channel antagonists (e.g., verapamil, a CYP3A4 substrate, and diltiazem, a CYP3A4 inhibitor) because of the possible potentiation of bradycardia, sinus arrest, and AV block; Effects of an inadvertent overdose of amiodarone HCl injection include hypotension, cardiogenic shock, bradycardia, AV block, and hepatotoxicity.

Amiodarone can be hard on the heart due to its potential to cause:

• Bradycardia
• Sinus arrest
• AV block
• Cardiogenic shock
• Hypotension when used alone or in combination with other medications, such as digoxin, ß-receptor blocking agents, or calcium channel antagonists 2, 2.

From the Research

Amiodarone's Impact on the Heart

• Amiodarone is considered a highly effective antiarrhythmic drug for the treatment of tachyarrhythmias, including ventricular arrhythmias and atrial fibrillation 3, 4, 5, 6, 7.
• It has been shown to prevent ventricular arrhythmias, such as frequent ventricular extrasystoles or nonsustained runs of ventricular tachycardia, as well as sustained ventricular tachycardia and ventricular fibrillation 3.
• Amiodarone is also effective in reducing the number of appropriate and inappropriate shocks in patients with an implantable cardioverter-defibrillator 3, 4.
• The drug has a low to negligible proarrhythmic action, meaning it does not aggravate heart failure and may even increase left ventricular ejection fraction and improve exercise capacity 5, 6.

Side Effects and Monitoring

• Long-term treatment with amiodarone can lead to side effects such as corneal microdeposits, blue-gray skin discoloration, photosensitivity, hypothyroidism, hyperthyroidism, peripheral neuropathy, optical neuritis, and hepatotoxicity 3, 4, 7.
• Irreversible, severe adverse effects, such as pulmonary toxicity, are very rare under the currently used maintenance dose of 200 mg/day 3.
• Regular monitoring, including laboratory values, lung function tests, and visual acuity, is necessary to minimize the risk of side effects 3, 4, 7.
• Clinicians should be aware of the potential interactions between amiodarone and other medications, such as warfarin, simvastatin, and atorvastatin, and many HIV antiretroviral medications 7.