Amiodarone, a class III antiarrhythmic, has become the drug of choice for the management of supraventricular and ventricular arrhythmias.1,2 Although not an FDA- approved indication, the use of amiodarone to treat atrial fibrillation is supported by practice guidelines from the American College of Cardiology/ American Heart Association (AHA) and the European Society of Cardiology.
Amiodarone, a class III antiarrhythmic, has become the drug of choice for the management of supraventricular and ventricular arrhythmias.1,2 Although not an FDA- approved indication, the use of amiodarone to treat atrial fibrillation is supported by practice guidelines from the American College of Cardiology/ American Heart Association (AHA) and the European Society of Cardiology.3 The AHA 2005 Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care suggest that amiodarone may be considered--before other antiarrhythmic therapy is given--for treatment of recurrent ventricular fibrillation and pulseless ventricular tachycardia that is resistant to CPR, precordial shocks, and vasopressors.4
A HIGH-RISK AGENT
Although amiodarone is widely used, it must be considered a high-risk agent. The drug has an extensive adverse-effect profile, including thyroid, hepatic, and pulmonary toxicities.5,6 Before therapy is initiated, baseline thyroid, liver, and pulmonary function tests are recommended. In addition, a baseline chest radiograph and eye examination should be performed. Because of the extremely long half-life of amiodarone, its effects can persist long after it has been discontinued.
Furthermore, amiodarone is associated with significant drug interactions, which require prudent monitoring and dosage adjustments. Our emphasis here is on the clinically relevant interactions; in Tables 1 through 5, we provide strategies to minimize risk.
MECHANISMS OF INTERACTIONCytochrome P-450 enzyme system. Amiodarone is metabolized hepatically and serves as a substrate primarily for cytochrome P-450 (CYP) 3A4. In addition, it is a potent inhibitor of CYP 3A4, 2C9, 2D6, and 1A2.2
As a result, concurrent use of CYP 3A4 inhibitors can cause levels of amiodarone to increase and the use of CYP 3A4 inducers can result in decreased concentrations of amiodarone. Numerous amiodarone drug interactions are associated with the inhibition of CYP 3A4 and other CYP isoenzymes by amiodarone, resulting in increased serum concentrations of the other medications (see Tables 1 through 5 for examples).
Transporter proteins. P-glycoproteins act as energy-dependent transmembrane efflux pumps that play a role in the distribution of medications such as digoxin, cyclosporine, and protease inhibitors.2 These proteins are widely distributed in the intestines, but they are also located among the endothelial cells of the blood-brain barrier, kidneys, liver, and other organs. Amiodarone can inhibit P-glycoprotein expression, which results in supratherapeutic levels of agents absorbed via this pathway.
Pharmacodynamic interaction. This interaction occurs when the pharmacologic response to a given agent is changed by the actions of another drug.2 An example of this type of interaction would be 2 drugs that produce additive effects.
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