Drug Profile

Pregnancy Warning

Amiodarone can cause fetal harm when administered to a pregnant woman. Fetal exposure may lead to heart, thyroid, neurological and growth abnormalities in newborns. Pregnant women should not use this drug.

Breast-feeding Warning

Amiodarone is excreted in human milk. Because of the potential for serious adverse effects in nursing infants, you should not take this drug while nursing.

FDA BLACK BOX WARNING

Cordarone (AMIODARONE) 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 life-threatening 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. In a retrospective survey of 192 patients with ventricular tachyarrhythmias, 84 required dose reduction and 18 required at least temporary discontinuation because of adverse effects, and several series have reported 15 to 20% overall frequencies of discontinuation due to adverse reactions. The time at which a previously controlled life-threatening arrhythmia will recur after discontinuation or dose adjustment is unpredictable, ranging from weeks to months.

The patient is obviously at great risk during this time and may need prolonged hospitalization. Attempts to substitute other antiarrhythmic agents when Cordarone must be stopped will be made difficult by the gradually, but unpredictably, changing amiodarone body burden. A similar problem exists when Cordarone is not effective; it still poses the risk of an interaction with whatever subsequent treatment is tried.

FDA BLACK BOX WARNING! INCREASED RISK OF DEATH

In the National Heart, Lung, and Blood Institute’s Cardiac Arrhythmia Suppression Trial (CAST) (a long-term, multicentered, randomized, double-blind study), in patients with asymptomatic non-life-threatening ventricular (the large chambers of the heart) arrhythmias (rhythm disturbances) who had a heart attack more than six days but less than two years previous, deaths or nonfatal cardiac arrest were seen in 7.7% of those patients treated with encainide or flecainide, members of the Class 1 group of antiarrhythmic drugs, compared to 3.0% in patients receiving an inactive sugar pill or placebo.

Because of the known ability of the Class 1 drugs, such as quinidine, to cause rhythm disturbances, and the lack of evidence of improved survival for any antiarrhythmic drug in patients without life-threatening heart rhythm disturbances, the use of the Class 1 drugs should be reserved for patients with life-threatening rhythm disturbances of the ventricles. These warnings now appear in the FDA-approved product labeling, or package insert, for all Class 1 drugs, including: disopyramide (NORPACE and generics), flecainide (TAMBOCOR), mexiletine (MEXITIL and generics), moricizine (ETHMOZINE), procainamide (PROCANBID and generics), propafenone (RYTHMOL), quinidine (DURAQUIN, QUINAGLUTE DURA-TABS, QUINIDEX, and generics), and tocainide (TONOCARD).

Warning

When this drug was used to treat rhythm disturbances of the small chambers of the heart (atria), it provided no survival advantage and a higher risk of serious adverse effects than older drugs such as digoxin, the beta-blockers, and the calcium channel blockers diltiazem and verapamil.[1],[2]

This drug is not approved by the FDA to treat rhythm disturbances of the atria.

Tell your doctor if you have or have had:

• allergies including iodine and lactose
• asthma
• high or low blood pressure
• other heart problems, such as bradycardia, congestive heart failure, heart block, or sinus node impairment
• liver problems
• thyroid problems
• pregnancy or are breast-feeding

Tell your doctor about any other drugs you take, including aspirin, herbs, vitamins, and other nonprescription products. Before you start this drug, request a thyroid test.

• Wear identification that you take amiodarone.
• Protect yourself from sunburn during and for several months following stopping treatment, using a sunblock. Wear protective brimmed hats, long sleeves, and pants.
• If you plan to have any surgery, including dental, tell your doctor that you take this drug.

• If you miss a dose, take it as soon as you remember, but skip it if it is almost time for your next scheduled dose. Notify your doctor if you miss two or more doses in a row. Do not take double doses.
• Do not share your medication with others.
• Take the drug at the same time(s) each day.
• Tablet must always be taken the same way, either with or without food.
• Do not break, chew, or crush this drug.
• Injection should be given by a health professional.
• If you stop taking this medication, remember that adverse effects can still last for several weeks or months.
• Store tablets at room temperature with lid on tightly. Do not store in the bathroom. Do not expose to heat, moisture, or strong light. Keep out of reach of children.

The following drugs, biologics (e.g., vaccines, therapeutic antibodies), or foods are listed in Evaluations of Drug Interactions 2003 as causing “highly clinically significant” or “clinically significant” interactions when used together with any of the drugs in this section. In some sections with multiple drugs, the interaction may have been reported for one but not all drugs in this section, but we include the interaction because the drugs in this section are similar to one another. We have also included potentially serious interactions listed in the drug’s FDA-approved professional package insert or in published medical journal articles. There may be other drugs, especially those in the families of drugs listed below, that also will react with this drug to cause severe adverse effects. Make sure to tell your doctor and pharmacist the drugs you are taking and tell them if you are taking any of these interacting drugs:

antihistamines, antipsychotics, AVELOX, beta-blockers, BETAPACE, calcium channel blockers, COUMADIN, CRIXIVAN, cyclosporine, digoxin, DILANTIN, diuretics, DURAQUIN, flecainide, grapefruit juice, halofantrine, indinavir, LANOXICAPS, LANOXIN, lidocaine, LOPRESSOR, metoprolol, mexiletine, MEXITIL, mizolastine, moxifloxacin, NORVIR, ORAP, phenytoin, pimozide, procainamide, PROCANBID, propafenone, QUINAGLUTE DURA-TABS, QUINIDEX, quinidine, RIFADIN, rifampin, ritonavir, RYTHMOL, SANDIMMUNE, sotalol, sparfloxacin, TAMBOCOR, warfarin, ZAGAM, zotepine.

Interactions with amiodarone can occur months after you stop taking amiodarone because it stays in the body for months after stopping treatment.

Call your doctor immediately if you experience:

• difficulty breathing
• dizziness, lightheadedness, or fainting
• fever
• cough
• unusual and uncontrolled movements of the body
• coldness
• dry eyes, sensitivity of eyes to light
• heartbeat becoming faster, slower, or irregular
• nervousness
• numbness or tingling in fingers or toes
• trembling or shaking of hands
• weakness of arms or legs
• swelling or painful scrotum
• sensitivity to heat or sunlight
• skin rash, blue-gray color, coldness, puffiness, or irritation at site of injection
• difficulty sleeping
• sweating
• swelling of legs or feet
• tiredness
• vision changes, blurred or blue-green halos around objects
• difficulty walking (weak arms and legs)
• undesired weight loss or gain
• yellowing of skin or eyes<

Call your doctor if these symptoms continue:

• appetite loss
• constipation
• dizziness
• flushing of face
• hair loss
• headache
• nausea or vomiting
• decreased sexual ability and interest
• sunburn
• bitter or metallic taste

Call your doctor if these symptoms occur after you stop treatment:

• cough
• slight fever
• painful breathing
• shortness of breath

Ask your doctor which of these tests should be done periodically while you are taking this drug:

• liver function tests
• chest examination
• broncoscopy
• chest X-ray
• heart function tests, such as electrocardiogram (ECG, EKG)
• gallium radionuclide scan
• eye examination
• plasma amiodarone determinations
• lung function determinations
• thyroid function determinations