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What is amiodarone, and how does it work (mechanism of action)?
Amiodarone is an oral and injectable drug that is used to correct abnormal rhythms of the heart. (It is an antiarrhythmic medication.) Although amiodarone has many side effects, some of which are severe and potentially fatal, it has been successful in treating many arrhythmias when other antiarrhythmic drugs have failed. Amiodarone is considered a "broad spectrum" antiarrhythmic medication, that is, it has multiple and complex effects on the electrical activity of the heart which is responsible for the heart's rhythm. Among its most important electrical effects are:
- a delay in the rate at which the heart's electrical system "recharges" after the heart contracts (repolarization);
- a prolongation in the electrical phase during which the heart's muscle cells are electrically stimulated (action potential);
- a slowing of the speed of electrical conduction (how fast each individual impulse is conducted through the heart's electrical system);
- a reduction in the rapidity of firing of the normal generator of electrical impulses in the heart (the heart's pacemaker);
- a slowing of conduction through various specialized electrical pathways (called accessory pathways) which can be responsible for arrhythmias.
In addition to being an antiarrhythmic medication, amiodarone also causes blood vessels to dilate (enlarge). This effect can result in a drop in blood pressure. Because of this effect, it also may be of benefit in patients with congestive heart failure.
Amiodarone was discovered in 1961 and approved by the FDA in December 1985.
What brand names are available for amiodarone?
Cordarone, Nextrone, Pacerone
Is amiodarone available as a generic drug?
Do I need a prescription for amiodarone?
What are the side effects of amiodarone?
Cordarone is intended for use only in patients with the indicated life-threatening arrhythmias because its use is accompanied by substantial toxicity.
Cordarone has several potentially fatal toxicities, the most important of which is pulmonary toxicity (hypersensitivity pneumonitis or interstitial/alveolar pneumonitis) that has resulted in clinically manifest disease at rates as high as 10 to 17% in some series of patients with ventricular arrhythmias given doses around 400 mg/day, and as abnormal diffusion capacity without symptoms in a much higher percentage of patients. Pulmonary toxicity has been fatal about 10% of the time. Liver injury is common with Cordarone, but is usually mild and evidenced only by abnormal liver enzymes. Overt liver disease can occur, however, and has been fatal in a few cases. Like other antiarrhythmics, Cordarone can exacerbate the arrhythmia, e.g., by making the arrhythmia less well tolerated or more difficult to reverse. This has occurred in 2 to 5% of patients in various series, and significant heart block or sinus bradycardia has been seen in 2 to 5%. All of these events should be manageable in the proper clinical setting in most cases. Although the frequency of such proarrhythmic events does not appear greater with Cordarone than with many other agents used in this population, the effects are prolonged when they occur.
Even in patients at high risk of arrhythmic death, in whom the toxicity of Cordarone is an acceptable risk, Cordarone poses major management problems that could be lifethreatening in a population at risk of sudden death, so that every effort should be made to utilize alternative agents first.
The difficulty of using Cordarone effectively and safely itself poses a significant risk to patients. Patients with the indicated arrhythmias must be hospitalized while the loading dose of Cordarone is given, and a response generally requires at least one week, usually two or more. Because absorption and elimination are variable, maintenance-dose selection is difficult, and it is not unusual to require dosage decrease or discontinuation of treatment.
Common side effects
Common side effects include:
- eye deposits,
- unsteady gait,
- weight loss,
- dizziness, and
- visual changes.
Amiodarone is also associated with:
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What is the dosage for amiodarone?
The recommended dosing schedule is an initial loading dose of 800-1600 mg daily for 1 to 3 weeks, followed by 600-800 mg daily for 1 month, then 400 mg daily for maintenance. Response should be closely monitored and dosing is individualized for each patient. Amiodarone may be administered once daily or given twice daily with meals to minimize stomach upset which is seen more frequently with higher doses.
Which drugs or supplements interact with amiodarone?
Amiodarone may interact with beta-blockers such as atenolol (Tenormin), propranolol (Inderal), metoprolol (Lopressor), or certain calcium channel blockers, such as verapamil (Calan, Isoptin, Verelan, Covera-HS) or diltiazem (Cardizem, Dilacor, Tiazac), resulting in an excessively slow heart rate or a block in the conduction of the electrical impulse through the heart.
Amiodarone increases the blood levels of digoxin (Lanoxin) when the two drugs are given together. It is recommended that the dose of digoxin be cut by 50% when amiodarone therapy is started. Flecainide (Tambocor) blood concentrations increase by more than 50% with amiodarone. Procainamide (Procan-SR, Pronestyl) and quinidine (Quinidex, Quinaglute) concentrations increase by 30%-50% during the first week of amiodarone therapy. Additive electrical effects occurs with these combinations, and worsening arrhythmias may occur as a result. Some experts recommend that the doses of these other drugs be reduced when amiodarone is started. Amiodarone can result in phenytoin (Dilantin) toxicity because it causes a two- or three-fold increase in blood concentrations of phenytoin. Symptoms of phenytoin toxicity including unsteady eye movement (temporary and reversible), tiredness and unsteady gait.
Ritonavir (Norvir), tipranavir (Aptivus), indinavir (Crixivan), and saquinavir (Invirase) can inhibit the enzyme that is responsible for the metabolism (break-down) of amiodarone. They should not be combined with amiodarone.
Amiodarone also can interact with tricyclic antidepressants (for example, amitriptyline [Endep, Elavil]), or phenothiazines (for example, chlorpromazine [Thorazine]) and potentially cause serious arrhythmias.
Amiodarone interacts with warfarin (Coumadin) and increases the risk of bleeding. The bleeding can be serious or even fatal. This effect can occur as early as 4-6 days after the start of the combination of drugs or can be delayed by a few weeks. Clotting studies probably should be done early during treatment with amiodarone among patients taking warfarin.
Amiodarone can interact with some cholesterol-lowering medicines of the statin class, such as simvastatin (Zocor), atorvastatin (Lipitor), and lovastatin (Mevacor), increasing the side effects of statins which include severe muscle breakdown, kidney failure or liver disease. This interaction is dose-related, meaning that lower doses of statins are safer than higher doses when used with amiodarone. An alternative statin, pravastatin (Pravachol), does not share this interaction and is safer in patients taking amiodarone.
Amiodarone inhibits the metabolism of dextromethorphan, the cough suppressant found in most over-the-counter (and some prescription) cough and cold medications (for example, Robitussin-DM). Although the significance of the interaction is unknown, these two drugs probably should not be taken together if possible.
Grapefruit juice may reduce the breakdown of amiodarone in the stomach leading to increased amiodarone blood levels. Grapefruit juice should be avoided during treatment with amiodarone.
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Is amiodarone safe to take if I'm pregnant or breastfeeding?
Amiodarone should not be used during pregnancy because it can cause fetal harm. There have been reports of congenital hypothyroidism or hyperthyroidism when amiodarone was administered during pregnancy.
What else should I know about amiodarone?
What preparations of amiodarone are available?
Tablets: 100, 200 mg. Injection: 50 mg/ml., 1.5 g/ml., 1.8 g/ml.
How should I keep amiodarone stored?
Tablets and injection should be kept at room temperature, 20 C to 25 C (68 F to 77 F).
Amiodarone (Cordarone, Nextrone, Pacerone) is an oral and injectable medication prescribed to correct abnormal rhythms of the heart. Side effects, drug interactions (an extensive list), warnings and precautions, and pregnancy efficacy should be reviewed prior to taking any medication.
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