(2-butylbenzofuran-3-yl)- [4-(2-diethylaminoethoxy)- 3,5-diiodo-phenyl]- methanone (as the hydrochloride salt)

Absorption
Oral
Bioavailability is 35% to 65%; T max is 3 to 7 h. Concentrations of 1 to 2.5 mg/L are effective with acceptable toxicity. Food increases rate and extent of absorption.

Distribution
Oral
Vd is about 60 L/kg.

Oral/IV
Crosses the placenta; excreted in breast milk. More than 96% protein bound.

IV
Rapidly distributed; serum concentrations decline to 10% of peak values within 30 to 45 min after the end of the infusion. Vd is 40 to 84 L/kg (amiodarone) and 68 to 168 L/kg (N-desethyl amiodarone [DEA]).

Metabolism
Metabolized by CYP3A4 to DEA (active).

Elimination
Eliminated primarily by hepatic excretion into bile; some enterohepatic recirculation may occur; negligible renal excretion. Biphasic elimination with initial 50% reduction in plasma levels after 2.5 to 10 days; terminal t ½ is 26 to 107 days (mean, about 53 days) (oral) and 20 to 47 days (IV). Not dialyzable.

Onset
2 to 3 days but more commonly 1 to 3 wk.

Special Populations
Elderly
Cl is lower and t ½ is increased; monitor closely.

Severe left ventricular dysfunction
The t ½ of DEA is prolonged; monitor closely.

Anticoagulants (eg, warfarin)
Warfarin PT increased by 100% after 3 to 4 days; reduce dose of anticoagulant by one third to one half.

Antihypertensives
Use with caution with beta blockers or calcium channel blockers because of the possible potentiation of bradycardia, sinus arrest, and AV block.

Azole antifungals/fluoroquinolones/macrolides
Reports of QTc prolongation with or without torsades de pointes may occur when used concomitantly with amiodarone.

Cardiac glycosides (eg, digoxin)
Digoxin levels are increased and may result in toxicity. Reduce digoxin dose by approximately 50% or discontinue.

Cholestyramine
Cholestyramine increases enterohepatic elimination of amiodarone and may reduce its serum levels and t ½ .

CYP3A4 inducers (eg, rifampin)
Amiodarone and the metabolite, desethylamiodarone, plasma levels may be reduced, decreasing the pharmacologic effect.

CYP3A4 inhibitors (eg, cimetidine, ritonavir)
Amiodarone plasma concentrations may be elevated, increasing the pharmacologic and adverse reactions.

Fentanyl
In combination with amiodarone may cause hypotension, bradycardia, and decreased cardiac output.

Grapefruit juice
Amiodarone plasma concentrations may be elevated, increasing the risk of side effects. Patients taking oral amiodarone should avoid grapefruit juice.

HMG-CoA reductase inhibitors (eg, simvastatin)
Simvastatin plasma levels may be elevated, increasing the risk of adverse reactions (eg, myopathy, rhabdomyolysis).

Lidocaine
Lidocaine plasma concentrations may be elevated, increasing the risk of seizures.

P-glycoprotein and CYP1A2, CYP2C9, CYP2D6, and CYP3A4 (eg, cyclosporine)
Plasma concentrations of drugs metabolized by these CYP enzymes or substrates of P-glycoprotein may be elevated, increasing the risk of side effects.

Protease inhibitors (eg, ritonavir)
Amiodarone plasma concentrations may be elevated, increasing the pharmacologic and adverse reactions.

St. John's wort
Amiodarone plasma levels may be reduced, decreasing the pharmacologic effects.

Trazodone
QT interval prolongation and torsade de pointes have been reported with coadministration.