Amiodarone: Top 3 Things to Know for Rate or Rhythm Control of AF

Both rate and rhythm control are options for treatment of atrial fibrillation (AF). Highly symptomatic patients or those with reduced left ventricular function as a result of poor rate control may benefit from a rhythm control strategy in the setting of paroxysmal AF. There are many choices for antiarrhythmic agents to promote conversion to sinus rhythm and to maintain sinus rhythm after cardioversion. In those patients with no coronary artery disease (CAD) and no structural heart disease (ie, heart failure [HF] or hypertrophy), class Ic antiarrhythmic medications [flecainide (Tambocor) and propafenone (Rythmol)] are the mainstays of rhythm control therapy. In patients with structural heart disease such as CAD, amiodarone can be used to restore and maintain sinus rhythm. For those in whom rate control is preferred but class Ic agents cannot be used (ie, asymptomatic patients with CAD or HF) amiodarone is an excellent adjunctive medication in addition to beta blockers or calcium channel blockers.

Here are 3 “must know” facts about amiodarone.

1. Class effect. In the Vaughan William classification, amiodarone has a primary class III effect (K+ channels) but actually has effects on all phases of the action potential with class 1 effects (Na+ channels); class II effects (beta blockade); and class IV effects (calcium channel blockade). Therefore, intravenous administration of amiodarone to a hypotensive patient with rapid AF can increase hypotension via beta blockade and calcium channel blockade. Amiodarone also decreases SA- and AV- nodal conduction, which may improve AF with rapid ventricular rate. However, following conversion from AF to sinus rhythm, patients on amiodarone therapy may experience prolonged bradycardia. These pleiotropic effects of amiodarone make it a reliable “go to” choice for patients with complex heart disease (ischemic heart disease, HF, etc) who are in need of rhythm control or an adjunctive rate control agent to treat AF. However, its many effects on cardiac conduction ought to be considered before it is selected as the therapy of choice.

2. Monitoring during amiodarone therapy. The drug’s many effects, which include prolongation of QTc, make routine ECG monitoring during chronic therapy essential-both to assess the QT interval and to determine rhythm.  Amiodarone can also affect the lungs, liver, and thyroid, both acutely and chronically. Therefore, baseline pulmonary and liver function tests (LFTs) and TSH levels are recommended. Thereafter annual chest x-ray, semiannual LFTs, and TSH levels taken every 3-6 months are recommended. Amiodarone has the potential to cause either clinical hyper- or hypothyroidism as well as thyrotoxicosis so clinical monitoring for related symptoms is critical. Other potential effects of amiodarone include photosensitivity, ocular complications, and neurotoxicity. Amiodarone can also have many drug-drug interactions. Particularly for patients on chronic therapy it is prudent to avoid concomitant use of agents that prolong the QT interval; drugs that have depressant effects on SA and AV conduction; and, drugs that inhibit or induce CYP3A activity.

3. Amiodarone pharmacology. “Loading” with amiodarone can be done in several ways – IV, PO, IV followed by PO, or IV and PO together. The loading regimen employed depends on the clinical indication and the rapidity of effect desired. More rapid loading slightly increases the risk of acute side effects. A standard rapid loading regimen (ie. in hospitalized patients) is IV followed by PO administration. For even more rapid loading (ie, in critically ill patients) IV and PO doses can be administered together. For stable outpatients, a PO load is generally recommended over the course of a week (400 mg po BID X 1 wk, followed by 200 mg po QD maintenance). For atrial arrhythmias, a total load of 6-8 grams is recommended. For ventricular arrhythmias, a total 8-10 grams is generally used. Amiodarone has a long half-life (40-55 days) for oral chronic therapy. Therefore, when switching from amiodarone to another class III agent such as dofetelide (Tikosyn), dronedarone, (Multaq), or sotalol (Betapace), reduced doses and close monitoring of the QTc are required.

In general, amiodarone is a highly effective antiarrhythmic agent with many indications and useful clinical applications but its use should be minimized (both the dose and the duration of therapy) due to its many possible side effects. For those patients in whom chronic therapy is the best choice, close monitoring by all clinicians involved in the patient’s care is essential.