Amiodarone hydrochloride
Amiodarone hydrochloride (Cordarone)
Amiodarone hydrochloride
(am-ee- OH-dah-rohn)
Pregnancy Category: D Cordarone Cordarone I.V. Pacerone (Rx)

Classification: Antiarrhythmic, class III

See Also: See also Antiarrhythmic Agents.

Action/Kinetics: Blocks sodium channels at rapid pacing frequencies, causing an increase in the duration of the myocardial cell action potential and refractory period, as well as alpha- and beta-adrenergic blockade. The drug decreases sinus rate, increases PR and QT intervals, results in development of U waves, and changes T-wave contour. After IV use, amiodarone relaxes vascular smooth muscle, reduces peripheral vascular resistance (afterload), and increases cardiac index slightly. No significant changes are seen in left ventricular ejection fraction after PO use. Absorption is slow and variable but food increases the rate and extent of absorption. Maximum plasma levels: 3-7 hr after a single dose. Onset: Several days up to 1-3 weeks. Drug may accumulate in the liver, lung, spleen, and adipose tissue. Therapeutic serum levels: 0.5-2.5 mcg/mL. t 1/2: Biphasic: initial t 1/2: 2.5-10 days; final t 1/2: 26-107 days. Effects may persist for several weeks or months after therapy is terminated. Effective plasma concentrations are difficult to predict although concentrations below 1 mg/L are usually ineffective, whereas those above 2.5 mg/L are not necessary. Neither amiodarone nor its metabolite, desethylamiodarone, is dialyzable.
Note: Due to medication errors, it has been proposed that the generic names for amrinone (Inocor) and amiodarone be changed. The proposed new names are inamrinone to replace amrinone and camiodarone to replace amiodarone.

Uses: Oral. Use should be reserved for life-threatening ventricular arrhythmias unresponsive to other therapy, such as recurrent ventricular fibrillation and recurrent, hemodynamically unstable ventricular tachycardia.
IV. Initial treatment and prophylaxis of frequently recurring ventricular fibrillation and hemodynamically unstable ventricular tachycardia in clients refractory to other therapy. Ventricular tachycardia/ventricular fibrillation clients unable to take PO medication. Investigational: Refractory sustained or paroxysmal atrial fibrillation, paroxysmal SVT, symptomatic atrial flutter. Also, low doses in CHF with decreased LV ejection fraction, exercise tolerance and ventricular arrhythmias.

Contraindications: Parenteral or PO use: Marked sinus bradycardia due to severe sinus node dysfunction, second- or third-degree AV block, syncope caused by bradycardia (except when used with a pacemaker). Cardiogenic shock (parenteral use only). Lactation.

Special Concerns: Safety and effectiveness in children have not been determined. The drug may be more sensitive in geriatric clients, especially in thyroid dysfunction. Carefully monitor the IV product in geriatric clients and in those with severe left ventricular dysfunction.

Side Effects: Adverse reactions, some potentially fatal, are common with doses greater than 400 mg/day. Pulmonary: Pulmonary infiltrates or fibrosis, interstitial/alveolar pneumonitis, hypersensitivity pneumonitis, alveolitis, pulmonary inflammation or fibrosis, ARDS (after parenteral use)lung edema, cough and progressive dyspnea. Oral use may cause a clinical syndrome of cough and progressive dyspnea accompanied by functional, radiographic, gallium scan, and pathologic data indicating pulmonary toxicity. CV: Worsening of arrhythmias, paroxysmal ventricular tachycardiaproarrhythmias, symptomatic bradycardia, sinus arrest, SA node dysfunction, CHF edema, hypotension (especially with IV use), cardiac conduction abnormalities, coagulation abnormalities, cardiac arrest (after IV use). IV use may result in atrial fibrillation, nodal arrhythmia, prolonged QT interval, and sinus bradycardia. Hepatic: Abnormal liver function tests, nonspecific hepatic disorders, cholestatic hepatitis, cirrhosis, hepatitis. CNS: Malaise, tremor, lack of coordination, fatigue, ataxia, paresthesias, peripheral neuropathy, abnormal involuntary movements, sleep disturbances, dizziness, insomnia, headache, decreased libido, abnormal gait. GI: N&V;, constipation, anorexia, abdominal pain, abnormal taste and smell, abnormal salivation. Ophthalmologic: Ophthalmic abnormalities, including optic neuropathy and/or optic neuritis (may progress to permanent blindness). Papilledema, corneal degeneration, photosensitivity, eye discomfort, scotoma, lens opacities, macular degeneration. Corneal microdeposits (asymptomatic) in clients on therapy for 6 months or more, photophobia, dry eyes, visual disturbances, blurred vision, halos. Dermatologic: Photosensitivity, solar dermatitis, blue discoloration of skin, rash, alopecia, spontaneous ecchymosis, flushing. Miscellaneous: Hypothyroidism or hyperthyroidism, vasculitis, flushing, pseudotumor cerebri, epididymitis, thrombocytopenia, angioedema. IV use may cause abnormal kidney function, Stevens-Johnson syndrome, respiratory syndrome, and shock.

Laboratory Test Alterations: AST, ALT, GGT. Alteration of thyroid function tests ( serum T ₄, serum T ₃).

Overdose Management: Symptoms: Bradycardia, hypotension, disorders of cardiac rhythm, cardiogenic shockAV block, hepatoxicity. Treatment: Use supportive treatment. Monitor cardiac rhythm and BP. Use a beta-adrenergic agonist or a pacemaker to treat bradycardia; treat hypotension due to insufficient tissue perfusion with a vasopressor or positive inotropic agents. Cholestyramine may hasten the reversal of side effects by increasing elimination. Drug is not dialyzable.

Drug Interactions: Anticoagulants / effect bleeding disorders Beta-adrenergic blocking agents / bradycardia and hypotension Calcium channel blockers / Risk of AV block with verapamil or diltiazem or hypotension with all calcium channel blockers Cholestyramine / Elimination of amiodarone serum levels and half-life Cimetidine / Serum levels of amiodarone Cyclosporine / Plasma drug levels elevated creatinine levels (even with cyclosporine doses) Dextromethorphan / Chronic use of PO amiodarone ( > 2 weeks) impairs drug metabolism Digoxin / Serum digoxin levels toxicity Disopyramide / QT prolongation possible arrhythmias Fentanyl / Possibility of hypotension, bradycardia, CO Flecainide / Plasma flecainide levels Indinavir / Plasma levels of amiodarone due to breakdown by liver Methotrexate / Chronic use of PO amiodarone ( > 2 weeks) impairs drug metabolism Procainamide / Serum procainamide levels toxicity Phenytoin / Serum phenytoin levels toxicity; also, amiodarone levels Quinidine / quinidine toxicity, including fatal cardiac arrhythmias Rifampin / Serum levels of amiodarone due to breakdown by the liver Ritonavir / Levels of amiodarone risk of amiodarone toxicity Theophylline / Serum theophylline levels toxicity (effects may not be seen for 1 week and may last for a prolonged period after drug is discontinued)

How Supplied: Injection: 50 mg/mL; Tablet: 200 mg

Dosage
Due to the drug's side effects, unusual pharmacokinetic properties, and difficult dosing schedule, administer amiodarone in a hospital only by physicians trained in treating life-threatening arrhythmias. Loading doses are required to ensure a reasonable onset of action.
?IV Infusion Life-threatening ventricular arrhythmias.
Loading dose, rapid: 150 mg over the first 10 minutes (15 mg/min). Then, slow loading dose: 360 mg over the next 6 hr (1 mg/min). Maintenance dose: 540 mg over the remaining 18 hr (0.5 mg/min). After the first 24 hr, continue maintenance infusion rate of 0.5 mg/min (720 mg/24 hr). This may be continued with monitoring for 2 to 3 weeks.
Once arrhythmias have been suppressed, the client may be switched to PO amiodarone. The following is intended only as a guideline for PO amiodarone dosage after IV infusion. IV infusion less than 1 week: Initial daily dose of PO amiodarone, 800-1,600 mg. IV infusion from 1 to 3 weeks: Initial daily dose of PO amiodarone, 600-800 mg. IV infusion longer than 3 weeks: Initial daily dose of PO amiodarone, 400 mg.