FDA Medwatch Reports (11/1/97-10/21/02)
Under the FOIA (Freedom of Information Act), all reports for the drug
Amiodarone (also called Cordarone or Pacerone) were obtained for the
last 5 years.
The FDA Medwatch Program is a voluntary reporting system. Physicians
file the majority of reports. It is estimated that only 1-10% of adverse
reactions to drugs are ever reported to the FDA.
The following is a compilation of reports concerning Amiodarone for the
past five years only. This drug has now been on the market for 17 years.
(Reports prior to 11/97 are archived and can be obtained only by
purchasing the entire FDA Medwatch database).
Total number of deaths reported = 452.
Total number of reports filed: over 3,900. The vast majority of these
reports involve side effects serious enough to require hospitalization.
Others involve permanent damage- blindness or permanent damage to lungs,
liver, thyroid or nervous system.
Causes of death: Respiratory failure due to lung damage, liver failure,
kidney failure, failure of multiple organs (e.g. lung, liver and
kidney), congestive heart failure, heart arrhythmias (including sinus
arrest, ventricular tachycardia, cardiogenic shock, and torsades de
pointes), stroke and bone marrow depression.
Other reported side effects according to type:
Lung Toxicity: pneumonitis, fibrosis, pulmonary edema, alveolitis,
pneumonia, pleural effusion, pulmonary hypertension, pulmonary
hemorrhage, Adult Respiratory Distress Syndrome (ARDS), bronchospasm,
shortness of breath, and cough.
Lung damage may be permanent.
Nervous System: neuropathy (numbness and tingling of arms or legs),
tremors, dizziness, imbalance, weakness, fatigue, malaise (generally not
feeling well), headache, abnormal gait (walking), speech disorders,
hoarseness, deafness, disturbances in taste or smell, tinnitus (ringing
in the ears), dysphagia (difficulty swallowing), nightmares, insomnia,
sleep disturbances, depression, suicide, amnesia, delusions,
hallucinations, aggression, delirium, anxiety, syncope (fainting),
confusion, dementia, stroke, convulsions, chorea (rapid involuntary
movements), aphasia (inability to speak), hiccups, muscle twitching,
panic attack, Parkinson's, Alzheimer's, Guillian Barre syndrome,
demyelination, paralysis (tongue, vocal cords, face, diaphragm and
other), increased intracranial pressure, encephalopathy, Bezoar (eating
hair or fuzz) and coma.
Remember recovery from neurological side effects "may be slow and
incomplete."
Liver toxicity: hepatitis, cirrhosis, ascites, liver failure, fatty
liver, liver necrosis and atrophy, biliary fibrosis and stasis and
elevations of liver enzymes and bilirubin.
Heart: worsening of existing arrhythmia, AV block, SA block, bundle
branch block, bradycardia (slow heart rate), tachycardia (fast heart
rate), atrial fibrillation, atrial flutter, ventricular tachycardia,
abnormal EKG (prolonged Qt interval, inverted T wave, pulsus bigeminus),
congestive heart failure, cardiac arrest, cardiac tamponade, ejection
fraction abnormal, palpitations, cardiomegaly (enlarged heart), chest
pain and worsening of angina.
Thyroid: abnormal levels of all thyroid hormones, hypothyroidism
(underactive thyroid), hyperthyroidism (overactive thyroid),
thyrotoxicosis, euthyroid sick syndrome, thyroiditis (inflammation of
the thyroid) and thyroid nodules.
Gastrointestinal disturbances: nausea, vomiting, constipation, diarrhea,
eructation (burping), dyspepsia (indigestion), anorexia (loss of
appetite), weight loss and weight gain, halitosis (bad breath),
increased saliva, tooth cavities, ileus (paralysis of intestines),
colitis, pancreatitis and elevations of amylase and lipase,
gastrointestinal bleeding, intestinal obstruction, mouth ulcers, melena
(black vomit or stool indicating bleeding) and abdominal pain.
Kidney: Elevations of BUN and creatinine and decreased creatinine
clearance (indicates kidney damage), nephritis, kidney stones, tubular
necrosis, acute renal failure and worsening of chronic renal failure.
Vision: 58 cases of blindness reported. Additional reports of optic
neuritis, optic neuropathy, optic atrophy, color blindness, cataracts,
papilloedema, retinal detachment, macular degeneration, night blindness,
loss of half the vision in one or both eyes, blurred vision, photophobia
(eye sensitivity to light) and corneal and lenticular deposits.
Swelling (sometimes life-threatening): arms, legs, joints, eyes, tongue,
face and throat and angioedema.
Skin: photosensitivity (skin easily sunburned), urticaria (hives),
erythema (redness of skin), blue discoloration of the skin, eczema,
pruritis (itching), dermatitis, flushing, psoriasis, pemphigoid and
toxic epidermal necrolysis (skin blisters and leaks fluid).
Muscles: elevations of CPK (indicates muscle damage), myositis
(inflammation of muscles), muscle fibrosis, muscle pain and spasms and
rhabdomyolosis (severe damage to the muscles that can lead to kidney
failure).
Other: fever, sweating, shivering, feeling cold, alopecia (hair loss),
nail disorders, dysarthria (pain in joints), leucopenia and neutropenia
(decreases in white blood cells increasing risk of infection),
thrombocytopenia (decreased platelets increasing risk of bleeding),
anemia, pancytopenia (decreases in all blood cells-white, red and
platelets), agranulocytosis, hemolytic anemia, bone marrow depression,
leukocytosis (increased white blood cell count), aplastic anemia,
eosinophilia, increases in antibodies and immunoglobulins, hypotension
(low blood pressure), hypertension (high blood pressure), increased
cholesterol levels, increased triglyceride levels, increases in
C-Reactive protein, increased uric acid levels, hypokalemia (decreased
potassium level), decreased magnesium levels, increased calcium levels,
splenomegaly (enlarged spleen), hyperglycemia (high blood sugars),
diabetes mellitus, worsening of diabetes, metabolic acidosis,
schleroderma, granuloma, Cushing's Syndrome, lymphadenopathy (enlarged
lymph nodes), amyloidosis, abnormal sed rate, vasculitis, phlebitis,
Stevens-Johnson Syndrome, parathyroid disorders, osteonecrosis,
epididymitis, male infertility, priapism, rhinitis (increased nasal
discharge), sinusitis, intolerance to alcohol, hyperpituitarism and
diabetes insipidus.
Birth defects in babies (mothers were given Amiodarone during
pregnancy): neonatal death, multiple developmental delays,
hypothyroidism, hyperthyroidism, central nervous system abnormality,
facial defects and nystagmus.
Reports of cancer: leukemia, bile duct, thyroid, lung and metastasis of
cancer.
Drug Interactions: Families of enzymes in the liver and intestines
metabolize most drugs. These enzyme families are given categories like
3A4. Other drugs inhibit some of these enzymes causing drug
interactions. Amiodarone inhibits 4 different enzyme families. They are
1A2, 2C9, 2D6 and 3A4. Therefore Amiodarone has the potential to
interact with over 100 hundred prescription and over the counter drugs.
According to the PDR, most of these drug interactions have "never been
formally investigated." To complicate matters, blood levels of
Amiodarone fluctuate for months after it is started. Therefore
interactions will be somewhat erratic and difficult to predict.
Amiodarone also remains in the body for months after it is stopped. So
drug interactions may also occur for months after use is discontinued.
Some of Amiodarone's side effects and deaths are due to drug
interactions. Amiodarone also interacts with general anesthesia. This
interaction increases risks of low blood pressure and slow heart rate
during surgery and increases risks of respiratory complications after
surgery. Inform your doctor/anesthesiologist/dentist about current or
recent use of Amiodarone prior to any surgery. For more information
about drug interactions see cytochrome p450 enzymes and drugs. Dave
Flockhart has an excellent site on these interactions. Drugs are listed
by their generic names only.
Medwatch reports are made when a drug is suspected (not proven) to have
caused the damage. The FDA uses these reports and other sources to
compile the information in the PDR (Physician's Desk Reference). Despite
the fact that the FDA Medwatch Program is anonymous and can be done by
telephone, few doctors report. If we are generous and use the FDA
estimate that 10% of actual damage is reported (some would say that only
1% is reported), we can conclude that 4,520 people have died as a result
of taking Amiodarone in the last 5 years alone. The other reports are
more difficult to quantify. Some patients had one or two side effects
listed, while others had multiple reactions. However, there are
thousands of these reports. Some of the damage will be permanent (e.g.
blindness, neurological disorders, thyroid problems, lung fibrosis and
liver damage).
The range of ages varies from one day old to over 90 years old. But the
most common ages are people in their sixties, seventies and eighties.
This group of people is less able to tolerate the toxicity of this drug.
Your body metabolizes most drugs through the liver (Amiodarone) or
kidneys. Beginning at age 40, your liver and kidneys begin to function
less efficiently, making them less able to metabolize drugs and other
substances. As you age, the water content of your body decreases making
drugs more concentrated in your body resulting in more side effects.
Older people and women also tend to have more fat in their bodies.
Amiodarone is lipophilic (it is attracted to fat). Therefore more of
this drug will accumulate in your body. Amiodarone causes the very
problems that are more common as we age. For all of these reasons,
Amiodarone use would appear to cause more problems in older people. The
Medwatch reports seem to confirm this fact. The FDA admits it was never
adequately tested in geriatric patients.