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Cordarone (Amiodarone Hydrochloride) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

Drug Interactions

Amiodarone is metabolized to desethylamiodarone by the cytochrome P450 (CYP450) enzyme group, specifically cytochrome P450 3A4 (CYP3A4) and CYP2C8. The CYP3A4 isoenzyme is present in both the liver and intestines (see “CLINICAL PHARMACOLOGY, Pharmacokinetics”). Amiodarone is an inhibitor of CYP3A4 and p-glycoprotein. Therefore, amiodarone has the potential for interactions with drugs or substances that may be substrates, inhibitors or inducers of CYP3A4 and substrates of p-glycoprotein. 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 and CYP2C8, drugs/substances that inhibit CYP3A4 may decrease the metabolism and increase serum concentrations of amiodarone. Reported examples include the following:

Protease inhibitors:

Protease inhibitors are known to inhibit CYP3A4 to varying degrees. A case report of one patient taking amiodarone 200 mg and indinavir 800 mg three times a day resulted in increases in amiodarone concentrations from 0.9 mg/L to 1.3 mg/L. DEA concentrations were not affected. There was no evidence of toxicity. Monitoring for amiodarone toxicity and serial measurement of amiodarone serum concentration during concomitant protease inhibitor therapy should be considered.

OVERDOSAGE

There have been cases, some fatal, of Cordarone overdose.

In addition to general supportive measures, the patient's cardiac rhythm and blood pressure should be monitored, and if bradycardia ensues, a β-adrenergic agonist or a pacemaker may be used. Hypotension with inadequate tissue perfusion should be treated with positive inotropic and/or vasopressor agents. Neither Cordarone nor its metabolite is dialyzable.

The acute oral LD50 of amiodarone HCl in mice and rats is greater than 3,000 mg/kg.

CONTRAINDICATIONS

Cordarone is contraindicated in patients with cardiogenic shock; severe sinus-node dysfunction, causing marked sinus bradycardia; second- or third-degree atrioventricular block; and when episodes of bradycardia have caused syncope (except when used in conjunction with a pacemaker).

Cordarone is contraindicated in patients with a known hypersensitivity to the drug or to any of its components, including iodine.

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