All concepts, explanations, trials, and studies have been re-written in plain English and may contain errors. I am not a doctor ----------------------------------------------------------- NOTE: You can make the print bigger with the font button on your browser! (It's usually a big "A") ----------------------------------------------------------- Title: The strange life of amiodarone By: Dr. Richard N. Fogoros From: heartdisease.about.com/library/weekly/aa042902a.htm Everyone offered amiodarone should understand the drug and its risks. Amiodarone was developed in Belgium in the 1960s as a drug for treating angina, and was quickly released in most countries, but not in the USA. Doctors quickly noticed that heart rhythm problems in patients taking amiodarone improved. Shortly, word filtered into the USA that amiodarone was an anti-arrhythmic drug that was said to "always work" and "have no side effects." Both statements proved false. In the late 1970s, American doctors started getting amiodarone from Canada and Europe to use in their patients with life-threatening irregular heart rhythm problems. The drug seemed so effective that by the mid 1980s, over ten thousand Americans were taking the drug. Americans studied the drug's effects more carefully than those overseas, and they found that amiodarone was indeed effective for irregular heart rhythms but it also causes bizarre side effects that doctors around the world seemed to have missed. By the mid 1980s, the FDA approved amiodarone for marketing in the USA. Foreign drug manufacturers had threatened to cut off the American supply, having supplied the drug for free to many Americans for over 5 years. American doctors convinced the FDA that not having the drug would be a medical disaster. So - unlike any other drug in modern history - amiodarone became FDA approved without rigorous, randomized clinical trials. AMIODARONE IS A STRANGE DRUG 1) It takes weeks to reach peak effectiveness. This is because amiodarone is stored in most of the body's tissues, so to "load" the body with the drug, all the tissues need to be saturated. Usually, amiodarone is used at very large doses for a week or two (loading), then the dose is reduced 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 afterward. 2) Amiodarone leaves the body very slowly. It is not eliminated by the liver or kidneys. It is lost when amiodarone-containing human cells are lost - such as skin cells or cells from the intestine, which are shed by the millions each day. So if you stop taking the drug, it still remains in your body for months. 3) 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. 4) Amiodarone has many different actions. It fits into two separate classes of anti-arrhythmic drugs - Class 1 and Class 3. It acts like a beta-blocker, it acts like a calcium channel blocker, it dilates blood vessels, and it can block the effect of thyroid hormone. SIDE EFFECTS Amiodarone's side effects are unusual. It took over 10 years for European doctors to admit that they had overlooked some incredibly serious side effects. The drug causes deposits to form on the cornea of the eyes in almost every patient. These deposits may not cause any problems but many patients complain of halos around things in their vision. Amiodarone can turn your skin blue-grey, getting worse over time. It is not certain that this clears up when the drug is stopped. In younger patients, this side effect can be devastating. Amiodarone sensitizes the skin to sunlight, so that even slight exposure can cause a nasty sunburn. People taking amiodarone may have to cover their bodies completely when going outside. Each amiodarone molecule has 4 iodine atoms, so a usual dose of amiodarone provides far more iodine to the body than is needed. The most common result is hypothyroidism - low thyroid. This is fairly easy to treat. However, some patients get hyperthyroidism - high thyroid - and this can be dangerous and hard to treat. Amiodarone can cause liver toxicity, so liver tests must be done regularly. It can also cause gastric reflux, from paralysis of the sphincter (valve) at the lower end of the esophagus. The most serious side effect of amiodarone is lung disease. The drug can cause an acute lung condition that looks like pneumonia, with sudden onset of cough and shortness of breath. This usually improves rapidly once the drug is stopped. The other kind of lung disease side effect is far more dangerous. It is a gradual, stiffening of the lungs that is often overlooked until it is already irreversible. This can happen a month after starting the drug or years after being on it with no problems. This condition can be fatal. IN CONCLUSION Amiodarone should be used for arrhythmias that are life-threatening or that are very disruptive to your life, and for which there are no other reasonable treatments. Despite its draw backs, the drug has helped many patients. However, because of its dangers, amiodarone use should be limited. By prescribing the drug, a doctor should commit himself to becoming a long-term partner with the patient. The patient must learn what to watch for and be vigilant for side effects. It is up to the patient to weigh potential benefits against potential risks and decide if this drug is for him or not. ======================================== Amiodarone is effective for treating irregular heart rhythms. However, it has a poor safety profile. Lung disease (pulmonary toxicity) is of great concern because this side effect can be fatal. This side effect was first described in 1980. Since then, we have seen that it occurs in between 5% and 17% of patients treated with amiodarone. Patients with amiodarone-induced lung problems usually show vague symptoms first - pneumonia or other lung and breathing complaints. Since heart failure patients often have trouble breathing, lung problems from amiodarone in such patients may go undiagnosed. This delayed diagnosis of amiodarone-induced lung toxicity increases risk of death. Diagnosing this side effect may be largely a matter of ruling out other lung problems. Diagnosis is helped by physical exam, imaging of the lungs, lung function tests, lab tests, and nuclear scans. Risk for amiodarone-induced pulmonary toxicity peaks in the first year of treatment, regardless of dose. In certain high-risk patients, even low dose amiodarone may quickly cause lung toxicity. Heart/lung surgery combined with oxygen use makes patients prone to it as well. Before starting amiodarone, at least one chest x-ray and lung function tests should be done, and any high-risk patients should have regular 3 month follow-ups to monitor for lung toxicity. Once diagnosed with amiodarone-induced lung toxicity, amiodarone should be immediately stopped if possible, keeping in mind that the heart rhythm problems are still there and must be treated somehow. Also, the toxic effect often persists because of the long half-life of the drug - up to 45 days. Otherwise, amiodarone can be stopped for several days and then restarted at the lowest effective dose. Non-drug therapy such as an ICD or doing an ablation may also be considered. Steroids (prednisone) may help reverse this lung problem in half of patients who don't have it severely yet. Because of the risk of relapse, steroid therapy probably should be continued for at least 6 months. However, despite steroid treatment, about 10 to 15% of patients still die. It is not possible to predict amiodarone- induced lung toxicity by measuring blood or tissue levels of the drug. The risk of toxicity increases with higher doses and longer length of therapy. It may correspond to total cumulative dose. Title: Careful Monitoring Required to Minimise the Damage of Amiodarone-Induced Pulmonary Toxicity Source: Drug & Ther Perspect 12(12):14-16, 1998 ====================================== Compared to amiodarone's frequent non-heart-related side effects - pulmonary fibrosis, liver and thyroid toxicity, and stomach, skin, central nervous system and eye problems, heart-related side effects are fairly rare - from 2% to 4%. This case shows the potential for life-threatening, bradycardia (too-low heart rate) with high oral loading doses of amiodarone. A 52 year old woman with a history of non-insulin- dependent diabetes, high blood pressure, a-fib, and thyroidectomy for goiter, was admitted to the hospital. She had lost consciousness, followed by lightheadedness, palpitations and chest pain. She had a heart rate of 215 beats per minute. After 100 mg IV lidocaine, her a-fib converted (with left bundle branch block). Her meds were digoxin, metoprolol, warfarin, furosemide, metazalone, glyburide and potassium. Cath showed no artery blockages and an EF of 50%. Oral amiodarone at 600 mg 3 times a day was started after the patient said she did not want any more invasive procedures. Her digoxin dose was cut in half. After 3 doses of amiodarone (total 1.8 grams) she collapsed suddenly. She was back in a-fib with complete heart block. The patient did not respond to atropine and epinephrine but was revived with invasive pacing. At the time of revival, her amiodarone level was 0.6 m g/ml (normal range 1 to 2.5m g/ml). Amiodarone was stopped along with digoxin and metoprolol. The patient recovered fully and had a pacemaker/ICD implanted. Amiodarone raises the blood level of some other drugs, especially digoxin. This can be very serious, and can cause the heart to stop. Hofman and Leisch studied the risk of too- low heart rates in 70 patients started on amiodarone with and without pre-existing arrhythmias. Half of these patients also took digoxin. Twenty-four percent of the patients with pre-existing arrhythmias developed too-low heart rate compared to none in the non-arrhythmia group. Overall risk for heart-related side effects with amiodarone is low. We believe that complete heart block is a rare but potentially life- threatening complication in patients getting high dose oral amiodarone who have pre-existing bundle branch block. In-hospital monitoring should be considered for such patients during the high dose loading phase of oral amiodarone. Title: Complete Heart Block With Cardiac Arrest During Oral Amiodarone Loading Authors: Christian Sticherling, Sharlene Day, Gregory Michaud Source: HeartWeb 4(9), 1999 ======================================= Amiodarone By Dr. Bramah Singh May 13, 1999 - Along with sotalol, amiodarone was the start of controlling heart arrhythmias by prolonging repolarization - the class 3 anti-arrhythmic action. Amiodarone has many complex actions. Amiodarone affects ALL heart tissues, such as the sinus node, the AV node, atrial cells, Purkinje fibers and the ventricular myocardium. Effects differ when the drug is given short-term versus when it is given over a long period of time. It is effective in restoring and maintaining normal rhythm in a-fib and it can prevent fast heart rate and ventricular fibrillation. It slows heart rate and conduction. Amiodarone blocks the sodium-channel (class 1 effect), inhibits nervous system stimulation (class 2 action), blocks potassium channels (class 3 action) and calcium channels (class 4 action). Amiodarone does not reduce the heart's beating strength and rarely causes arrhythmia, making it an option for heart failure patients. Amiodarone is a powerful suppressant of PVCs and runs of fast heart rate. It may reduce sudden death and prolong survival in certain groups of patients. It is now generally agreed that for many patients with ventricular tachycardia and fibrillation, the preferred therapy is ICD. However, amiodarone may also be required. Intravenous Amiodarone IV amiodarone may control fast heart rate and fibrillation in hospitalized heart attack patients who do not respond to other drugs. Such patients are treated with IV lidocaine, procainamide and bretylium. Some studies suggest that IV amiodarone in this setting is an important addition to anti-arrhythmia therapy in these patients. Three doses - 125 mg, 500 mg, 1000 mg per 24 hours) of amiodarone were compared in this group of patients. The highest dose was best for preventing arrhythmia and was well tolerated. Possible Side Effects There is an increasing tendency to use lower doses of amiodarone to control arrhythmia. While the side effect potential of the drug cannot be eliminated, it can be reduced. The major bad side effects are lung toxicity serious liver toxicity, skin changes (reversible), and eye changes, which rarely may become serious. The effects of amiodarone on thyroid function need to be monitored regularly, since it can cause both hypo- and hyperthyroidism.