I'm diagnosed with pulmonary fibrosis due to amiodarone toxicity

On August 11, 2011, I was given what amounts to a death sentence. I was told I had been diagnosed with pulmonary fibrosis induced by amiodarone toxicity. 

Pulmonary fibrosis is progressive, and there is as yet no treatment for curing it. Normal prognosis is death in two to four years. Often death comes faster, especially when the fibrosis is caused by amiodarone poisoning. It is rare for someone with pulmonary fibrosis to survive for five years or more. 

Pulmonary fibrosis is a scarring of the tissue in the lungs. As pulmonary tissue hardens, it becomes increasingly difficult for the alveoli of the lungs to re-oxygenate blood supply. The victim eventually dies of oxygen deprivation.

There are several medicines that hold promise for slowing the progression of the fibrosis. One is an over-the-counter antioxidant called L-Cysteine Hcl. I'm taking six hundred mg. of that three times a day. There's also a clinical trial just launched for a drug already in use in Europe called pirfenidone (being marketed in Europe as Ebriet). Atlanta is one of the centers for the clinical trial, and I'm in the process of enrolling.

The only remedy for a fibrotic lung is a lung transplant. For that, transplant centers use a one hundred-point scoring system to determine who gets transplants. People over sixty-five―that includes me, at seventy-three―seldom score high enough to get a transplant. But there are exceptions. One of the men in my pulmonary fibrosis support group at Piedmont Hospital is in his early 70s and just got a double transplant. I'm in the process of being evaluated and scored by Emory University Hospitals in Atlanta, the local lung transplant center.

How did I get pulmonary fibrosis?

In July 2010, an electrophysiologist in a group practice in Atlanta prescribed 200 mg. daily of amiodarone for me. The purpose was to control non-life-threatening premature ventricular contractions of my heart. 

The electrophysiologist did not warn me that amiodarone is a deadly poison for seventeen percent of the population. He did not follow U.S. Food and Drug Administration guidelines in prescribing the medication―the FDA says it’s to be used only in life-threatening situations, and then only as a treatment of last resort.

Already by November 2010, family members were noticing the shortness of breath that had overtaken me so gradually that I didn’t recognize it.

By December 2010, when I had an annual physical with a cardiologist at the same practice as the electrophysiologist, I complained of shortness of breath and cyanosis around my fingernails, both symptoms of amiodarone poisoning. In amiodarone poisoning, cyanosis―a blue coloration indicating oxygen deprivation in the blood―occurs around the fingernails. 

The cardiologist who saw me that day didn’t connect the obvious symptoms of amiodarone poisoning with the symptoms I was displaying, although he knew I was taking amiodarone. 

The cardiologist took two chest x-rays as part of my physical, and the radiologist who read them noted the beginnings of interstitial lung disease―but no warning came to me of what the radiologist saw.

By January 2011, I was becoming increasingly aware of my declining lung capacity and difficulty breathing. My wife Kathie and I began to talk to nurses who lived in our neighborhood, asking if they had any ideas of what could be causing my breathing difficulties. We still hadn't figured out that I was suffering from amiodarone poisoning. But the nurses did. Three of them―including his own assistant―ganged up on the electrophysiologist in early February 2011 and told him they thought I had amiodarone poisoning. He  told his assistant to call me to tell me to stop taking the amiodarone―without any explanation of why.

When I had a follow-up appointment in the spring of 2011 with the cardiologist, and told him that the electrophysiologist had discontinued the amiodarone in February, the cardiologist went back to the radiologist’s description of my December chest x-rays and finally saw the warning about the developing interstitial lung disease―another term for idiopathic pulmonary fibrosis.

I was soon thereafter given an echocardiogram that ruled out congestive heart disease as the cause of my symptoms. The technician who administered that test told me my heart was as good as an astronaut’s. Chronic obstructive pulmonary disease (COPD) was also ruled out.

On August 11, 2011, the pulmonologist I was seeing told me that he and the electrophysiologist had discussed my case and agreed that what I had was pulmonary fibrosis brought on by amiodarone toxicity.

So there you are. Based on the longevity of males in my family, I should be expecting another ten  years of healthy, enjoyable life. But that is not likely now. 

I certainly won’t be the first person to die of amiodarone poisoning. There are many cases on record. I may discuss a few of them in future postings on this blog. I don’t know how many postings there will be, because I don’t know how often I will write a post, or more importantly, how much time I have left to write them.

Most of us don’t know when death will come. As a result, we fail to do many things that need to be done to protect those we love and leave behind.

I’ve been giving a lot of thought to the things that need to be done―to the physical things like writing a will (that’s done), and to the spiritual things like preparing the spirit for the crossing over (not done yet, but I’m working on it).

Hopefully, in future posts, I can provide information of both a pragmatic and spiritual nature that will be helpful to others facing the same predicament as me.

The strange history of amiodarone

As I've noted in other posts, I'm dying of pulmonary fibrosis caused by amiodarone toxicity. Amiodarone is a drug that the U.S. Food and Drug Administration recommends for use only in life-threatening situations. An electrophysiologist prescribed the drug for me for a non-life-threatening condition―occasional premature ventricular contractions that posed no danger to my life.

According to About.com Guide Dr. Richard N. Fogoros, M.D., amiodarone, sold under the brand names Cordarone and Pacerone, is the most effective, and certainly the strangest, antiarrhythmic drug ever developed. 

One of the strangest aspects of the drug is its history. It is a history that explains much about why, to this day, many of the more unusual features of the drug are poorly understood by many doctors who prescribe it. 

Amiodarone was developed by a Belgian company in 1961 as a drug for treating angina (chest discomfort related to coronary artery disease), and quickly became a popular anti-angina drug in Europe and South America. However, by the choice of the drug company (probably to avoid the unusually tough American regulatory environment), amiodarone was not offered for release in the United States. 

After a few years a physician in Argentina, Dr. Mauricio Rosenbaum, noticed that amiodarone seemed to reduce cardiac arrhythmias in his patients with heart disease. He began using the drug extensively for heart rhythm disturbances, and then began to publish his results, which were extraordinarily impressive. Clinicians from all over the world (except in the United States) quickly began using the drug to treat cardiac arrhythmias of all sorts. The reputation of amiodarone spread far and wide―amiodarone, the word was, was a unique antiarrhythmic drug that almost always worked, and had virtually no side effects. 

Both of these assertions, of course, proved false.

Beginning in the late 1970s, American electrophysiologists (heart rhythm specialists) began to obtain amiodarone from Canada and Europe to use in their patients with life-threatening arrhythmias who did not respond to any other drugs. The Food and Drug Administration (FDA), the federal agency that oversees drug safety, sanctioned this activity on a compassionate-use basis. 

The early word from Americans seemed to confirm what was being said all over the world―amiodarone was very safe and very effective. Electrophysiologists by the early 1980s were driving to a customs office to clear a foreign shipment of amiodarone, provided free by the Belgian drug company. 

Within a few years, more than 10,000 American patients with potentially lethal arrhythmias were estimated to be receiving amiodarone. Of course, because of the way amiodarone was being distributed, nobody really knew how many patients were receiving the drug. More importantly, because the FDA was not involved in any of this, except to approve of the use of the drug for compassionate reasons, nobody was compiling information on the drug's effectiveness or safety. 

However, many American doctors studied the effects of amiodarone on their own patients somewhat more rigorously than their overseas colleagues had done. As a result, within a year or two the view of amiodarone began to change. 

Amiodarone was indeed more effective at suppressing arrhythmias than any other drug, though by no means as effective as had been advertised, but it produced a bizarre series of side effects―including difficult thyroid disorders, skin discoloration, and potentially life-threatening lung toxicity―that doctors around the world seemed to have missed. The side effects had been missed, for the most part, because they were so unusual and unexpected, and because their onset tended to be insidious and late. 

When the side effects of amiodarone began to be described in medical publications, the FDA became reluctant to approve the drug. However, the FDA soon had little choice. In the mid-1980s, the foreign manufacturers of amiodarone threatened to cut off the American supply. Simply cutting Americans off from the drug would produce a medical (and hence, possibly a political) disaster. So, in 1985, in sharp contrast to any other drug in modern history, amiodarone became FDA-approved without rigorous FDA-sanctioned randomized clinical trials.

Respectful of the drug's newly discovered and very troublesome toxicity, the FDA approved the drug only for life-threatening arrhythmias for which no other treatment was feasible. 

The FDA urged the manufacturers to conduct randomized clinical trials to gain formal approval for indications such as atrial fibrillation, noting that conducting such trials would teach us much about true incidence and seriousness of the drug's side effects. Those trials were never done―possibly because such trials are very expensive, and by this time the patent on amiodarone was expiring, opening the door for generic manufacturers to begin selling it―and the original restrictions on the use of amiodarone have persisted to this day. 

The strange history of amiodarone may explain why some doctors who prescribe this drug seem unaware of the breadth and the subtle nature of many of its side effects―and why some of them do not adequately monitor their patients who take amiodarone, or fully inform their patients as to what to watch out for.

Physician guidelines and precautions for the prescribing of amiodarone

I’ve noted in other posts that I’ve been diagnosed with pulmonary fibrosis due to amiodarone toxicity.

Pulmonary fibrosis is a progressive, fatal disease. There is no cure for it. Death usually occurs in two to four years, although sometimes it comes faster, and sometimes victims live longer.

Amiodarone is a drug with dangerous side effects. It is toxic for about seventeen percent of those who take it.

Following are some U.S. Food and Drug Administration guidelines for physicians prescribing the drug. I’ve highlighted some of the more significant cautions in red.

Pulmonary Toxicity:

“There have been post-marketing reports of acute-onset (days to weeks) pulmonary injury in patients treated with oral Amiodarone with or without initial I.V. therapy. Findings have included pulmonary infiltrates and/or X-ray, pulmonary alveolar hemorrhage, pleural effusion, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, and hypoxia. Some cases have progressed to respiratory failure and/or death. Post-marketing reports describe cases of pulmonary toxicity in patients treated with low doses of Amiodarone; however, reports  suggest that the use of lower loading and maintenance doses of Amiodarone are associated with a decreased incidence of Amiodarone-induced pulmonary toxicity.

“Amiodarone hydrochloride tablets may cause a clinical syndrome of cough and progressive dyspnea accompanied by functional, radiographic, gallium-scan, and pathological data consistent with pulmonary toxicity, the frequency of which varies from 2 to 7% in most published reports, but is as high as 10 to 17% in some reports. Therefore, when Amiodarone therapy is initiated, a baseline chest X-ray and pulmonary-function tests, including diffusion capacity, should be performed. The patient should return for a history, physical exam, and chest X-ray every 3 to 6 months.

“Pulmonary toxicity secondary to Amiodarone seems to result from either indirect or direct toxicity as represented by hypersensitivity pneumonitis (including eosinophilic pneumonia) or interstitial/alveolar pneumonitis, respectively.

“Patients with preexisting pulmonary disease have a poorer prognosis if pulmonary toxicity develops.

Hypersensitivity pneumonitis usually appears earlier in the course of therapy, and rechallenging these patients with Amiodarone results in a more rapid recurrence of greater severity.

Bronchoalveolar lavage is the procedure of choice to confirm this diagnosis, which can be made when a T suppressor/cytotoxic (CD8-positive) lymphocytosis is noted. Steroid therapy should be instituted and Amiodarone therapy discontinued in these patients.

“Interstitial/alveolar pneumonitis may result from the release of oxygen radicals and/or phospholipidosis and is characterized by findings of diffuse alveolar damage, interstitial pneumonitis or fibrosis in lung biopsy specimens. Phospholipidosis (foamy cells, foamy macrophages), due to inhibition of phospholipase, will be present in most cases of Amiodarone-induced pulmonary toxicity; however, these changes also are present in approximately 50% of all patients on Amiodarone therapy. These cells should be used as markers of therapy, but not as evidence of toxicity. A diagnosis of Amiodarone-induced interstitial/alveolar pneumonitis should lead, at a minimum, to dose reduction or, preferably, to withdrawal of the Amiodarone to establish reversibility, especially if other acceptable antiarrhythmic therapies are available. Where these measures have been instituted, a reduction in symptoms of Amiodarone-induced pulmonary toxicity was usually noted within the first week, and a clinical improvement was greatest in the first two to three weeks. Chest X-ray changes usually resolve within two to four months. According to some experts, steroids may prove beneficial. Prednisone in doses of 40 to 60 mg/day or equivalent doses of other steroids have been given and tapered over the course of several weeks depending upon the condition of the patient. In some cases rechallenge with Amiodarone at a lower dose has not resulted in return of toxicity.

“In a patient receiving Amiodarone, any new respiratory symptoms should suggest the possibility of pulmonary toxicity, and the history, physical exam, chest X-ray, and pulmonary-function tests (with diffusion capacity) should be repeated and evaluated. A 15% decrease in diffusion capacity has a high sensitivity but only a moderate specificity for pulmonary toxicity; as the decrease in diffusion capacity approaches 30%, the sensitivity decreases but the specificity increases. A gallium-scan also may be performed as part of the diagnostic workup.

“Fatalities, secondary to pulmonary toxicity, have occurred in approximately 10% of cases. However, in patients with life-threatening arrhythmias, discontinuation of Amiodarone therapy due to suspected drug-induced pulmonary toxicity should be undertaken with caution, as the most common cause of death in these patients is sudden cardiac death. Therefore, every effort should be made to rule out other causes of respiratory impairment (i.e., congestive heart failure with Swan-Ganz catheterization if necessary, respiratory infection, pulmonary embolism, malignancy, etc.) before discontinuing Amiodarone in these patients. In addition, bronchoalveolar lavage, transbronchial lung biopsy and/or open lung biopsy may be necessary to confirm the diagnosis, especially in those cases where no acceptable alternative therapy is available.

“If a diagnosis of Amiodarone-induced hypersensitivity pneumonitis is made, Amiodarone should be discontinued, and treatment with steroids should be instituted. If a diagnosis of Amiodarone-induced interstitial/alveolar pneumonitis is made, steroid therapy should be instituted and, preferably, Amiodarone discontinued or, at a minimum, reduced in dosage. Some cases of Amiodarone-induced interstitial/alveolar pneumonitis may resolve following a reduction in Amiodarone dosage in conjunction with the administration of steroids. In some patients, rechallenge at a lower dose has not resulted in return of interstitial/alveolar pneumonitis; however, in some patients (perhaps because of severe alveolar damage) the pulmonary lesions have not been reversible.”

The doctor who prescribed amiodarone for me gave no warning of the pulmonary dangers, and did not follow recommended FDA practice in my case. He cavalierly prescribed amiodarone without a baseline x-ray, without pulmonary-function tests, without a three-month follow-up, and without any in-patient monitoring. It took three nurses ganging up on him eight months later for him to finally come to the realization that I had been poisoned.

Despite the doctor's rationalization that it takes "years" for amiodarone to "have any effects," there are numerous cases on record of fatal pulmonary fibrosis developing in a few months, and some in which pulmonary toxicity was manifested itself in a matter of days.

While this post is a bit technical, I've included  it because it might serve as a warning to others for whom amiodarone is cavalierly prescribed.