Amiodarone

Mechanism :

Amiodarone is a class three anti-arrhythmic drug. It works in two ways (1) prolongation of the myocardial cell-action potential duration and refractory period and (2) non-competitive alpha- and beta-adrenergic inhibition.

Indication :

Refractory supraventricular tachycardia
Junctional ectopic tachycardia
Atrial fibrillation
Atrial flutter
Shock resistant ventricular fibrillation
Pulseless tachycardia in resuscitation

Contraindications :

Cardiogenic shock;

Severe sinus-node dysfunction, causing marked sinus bradycardia;

Second- or third-degree atrioventricular block;

Bradycardia, that has caused syncope.

Known hypersensitivity to the drug or to any of its components, including iodine.

Dosing :

Supraventricular tachycardia:

Oral: 10 to 20 mg/kg/day in 2 divided doses for 7 to 10 days; then reduce to 5 to 10 mg/kg/day once daily for 2 to 7 months.

Tachyarrhythmia, including junctional ectopic tachycardia (JET), paroxysmal supraventricular tachycardia (PSVT):

IV: 5 mg/kg given over 60 minutes. May repeat again. Max: 15 mg/kg/day.

Continuous IV infusion: Initial: 5 mcg/kg/min; increase incrementally as clinically needed; upto 15 mcg/kg/min.

Oral: 10 to 15 mg/kg/day in 1 to 2 divided doses/day for 4 to 14 days or until adequate control of arrhythmia; dosage should then be reduced to 5 mg/kg/day given once daily for several weeks.

Shock refractory VF or pulseless VT:

IV: 5 mg/kg (Maximum: 300 mg/dose) rapid bolus; may repeat twice up to a maximum total dose of 15 mg/kg.

Adverse Effect :

Malaise, fatigue, tremors, ataxia, peripheral neuropathy, nausea, vomiting, constipation, anorexia, increase liver enzymes, optic neuropathy, papilledema, corneal degeneration, photosensitivity, lens opacities, macular degeneration, photosensitivity rash, exacerbation of arrhythmias, congestive heart failure, bradycardia, hypothyroidism, thrombocytopenia.

Interaction :

Histamine H1 antagonists: Interval prolongation and torsade de pointes.
Histamine H2 antagonists: Cimetidine inhibits CYP3A4 and can increase serum amiodarone levels.
Antidepressants: QT interval prolongation and torsade de pointes.
Protease inhibitors: Increases in amiodarone concentrations.
Fluoroquinolones, Macrolide Antibiotics, and Azoles: Known to cause QTc prolongation
Cyclosporine: persistently elevated plasma concentrations of cyclosporine resulting in elevated creatinine.
HMG-CoA Reductase Inhibitors: Myopathy/rhabdomyolysis.
Digoxin: Increase in the serum digoxin concentration that may reach toxic levels with resultant clinical toxicity.
Quinidine, Procainamide, Disopyramide, and Phenytoin: Increased steady-state levels of quinidine, procainamide, and phenytoin during concomitant therapy with amiodarone..
Antihypertensives: ß-receptor blocking agents or calcium channel antagonists because of the possible potentiation of bradycardia, sinus arrest, and AV block.
Anticoagulants: Potentiation of warfarin-type anticoagulant response is almost always seen in patients receiving amiodarone and can result in serious or fatal bleeding.
Rifampin: Decrease in serum concentrations of amiodarone.

Hepatic Dose :

Dosage reduction with frequent monitoring of liver functions is advisable. Amiodarone dose should be reduced, or the treatment discontinued if the transaminases > 3 times upper limit of normal (ULN). If jaundice appears, discontinue therapy.