Amiodarone is metabolized to desethylamiodarone by the cytochrome P450 (CYP450) enzyme group, specifically cytochrome P450 3A4 (CYP3A4). This isoenzyme is present in both the liver and intestines (see " CLINICAL PHARMACOLOGY, Pharmacokinetics "). Amiodarone is also known to be an inhibitor of CYP3A4. Therefore, amiodarone has the potential for interactions with drugs or substances that may be substrates, inhibitors or inducers of CYP3A4. While only a limited number of in vivo drug-drug interactions with amiodarone have been reported, the potential for other interactions should be anticipated. This is especially important for drugs associated with serious toxicity, such as other antiarrhythmics. If such drugs are needed, their dose should be reassessed and, where appropriate, plasma concentration measured.
In view of the long and variable half-life of amiodarone, potential for drug interactions exists not only with concomitant medication but also with drugs administered after discontinuation of amiodarone.
Since amiodarone is a substrate for CYP3A4, drugs/substances that inhibit CYP3A4 may decrease the metabolism and increase serum concentrations of amiodarone, with the potential for toxic effects. Reported examples of this interaction include the following:
There have been cases, some fatal, of amiodarone HCl overdose.
In addition to general supportive measures, the patient's cardiac rhythm and blood pressure should be monitored, and if bradycardia ensues, a (beta)-adrenergic agonist or a pacemaker may be used. Hypotension with inadequate tissue perfusion should be treated with positive inotropic and/or vasopressor agents. Neither amiodarone nor its metabolite is dialyzable.
The acute oral LD50 of amiodarone HCI in mice and rats is greater than 3,000 mg/kg.
Pacerone® is contraindicated in severe sinus-node dysfunction, causing marked sinus bradycardia; second- and third-degree atrioventricular block; and when episodes of bradycardia have caused syncope (except when used in conjunction with a pacemaker).
Pacerone® is contraindicated in patients with a known hypersensitivity to the drug.