Amiodarone - uniquely effective, but uniquely toxic
Updated January 04, 2015.
Amiodarone (Cordarone, Pacerone) is the most effective, and certainly the strangest, antiarrhythmic drug ever developed. Anyone being treated with amiodarone should understand the idiosyncrasies - and the risks - associated with this drug.
Unusual features of amiodarone
Amiodarone has several characteristics that make it unique.
First, the drug takes weeks to achieve its maximum effectiveness.
This is because amiodarone is stored in most of the tissues of the body, and to "load" the body with the drug, all the tissues need to be saturated. The typical "loading" regimen of amiodarone, therefore, is to use very large doses for a week or two, then taper the dosage over the next month or so. It is not unusual to give patients 1200 or 1600 mg per day at first, and then maintain them on as little as 100 or 200 mg per day chronically.
Second, amiodarone leaves the body very, very slowly. It is not excreted (like most drugs) by the liver or the kidneys. It is lost when amiodarone-containing human cells are lost - such as skin cells or cells from the GI tract, which are shed by the millions each day. Thus, if it is decided that one needs to stop amiodarone, the drug remains in the body in measurable quantities for months and months. The "half life" of the drug, in contrast to most other drugs, is measured in weeks instead of hours.
Third, because amiodarone is stored in many different kinds of tissues, it can produce side effects affecting many different organs.
Some of these side effects take months or years to develop, so it is never true that one can stop being vigilant.
Fourth, amiodarone works through many different mechanisms, unlike most drugs. It fits into two separate categories of antiarrhythmic drugs (Class I and Class III, for what it's worth). It acts as a beta blocker and also as a calcium blocker. It dilates blood vessels, and and it often acts to "block" the effect of thyroid horomone.
The Side Effects of Amiodarone
The side effects of amiodarone often take weeks or months to develop, so must be watched for as long as the drug is used. These side effects tend to be very unusual for antiarrhytmic drugs - or for any drug, for that matter - and they may take months or years to appear. For this reason, it took more than a decade for doctors to recognize many of these toxicities were even associated with amiodarone. To this day, doctors all too often fail to monitor their patients taking amiodarone long enough, and diligently enough, to recognize that the drug is producing problems.
Amiodarone commonly causes deposits to form on the cornea of the eyes - often leading to "halo-vision," where looking at bright lights at night is like looking at the moon on a foggy evening.
Amiodarone can cause a very disfiguring blue-grey discoloration of the skin, generally in areas of sun exposure.
Amiodarone often sensitizes the skin to sunlight, so that even trivial exposure can cause a fairly nasty sunburn.
Amiodarone can cause thyroid disorders, both hypothyroidism (low thyroid) and hyperthyroidism (high thyroid.) These thyroid problems are common with amiodarone, and can be unusually difficult to recognize and treat. For this reason, patients taking this drug should have their thyroid function routinely monitored.
Amiodarone can cause liver toxicity, so liver enzymes need to be monitored periodically. It can also cause rather severe gastric reflux.
The most serious side effect of amiodarone is lung toxicity. This can take several forms, from an acute lung syndrome that makes patients desperately ill, requires intensive care, and often results in death, to a more insidious, gradual, unnoticeable, "stiffening" of the lungs that both the doctor and patient can overlook until finally severe, probably irreversible lung damage is done.
When should amiodarone be used?
Amiodarone should be used for arrhythmias that are life-threatening or that are very disruptive to one's life, and for which there are no other reasonable therapies. Despite its drawbacks the drug has helped tens of thousands of patients, and has restored them to a nearly normal life. When used appropriately, amiodarone can be a major benefit to patients. But because of the potential toxicity its use should be limited. The doctor should, by prescribing the drug, be committing him/herself to becoming a long-term partner of the patient. He/she should carefully coach the patient on what problems to look for, and together they should be ever vigilant for the side effects of the drug.
Sources:
Goldschlager N, Epstein AE, Naccarelli GV, et al. A practical guide for clinicians who treat patients with amiodarone: 2007. Heart Rhythm 2007; 4:1250.
Vassallo P, Trohman RG. Prescribing amiodarone: an evidence-based review of clinical indications. JAMA 2007; 298:1312.
