There are growing safety concerns over the anti-arrhythmia drug Multaq, (dronedarone), which is manufactured and marketed by Sanofi-Aventis and has generated a great deal of controversy and concern in just a few short years.

Multaq was first approved by the Food & Drug Administration (“FDA”) in 2009 for use as an anti-arrhythmic drug in heart patients with paroxysmal or persistent atrial fibrillation.  Atrial fibrillation is essentially an irregular heartbeat that may be a sign of an asymptomatic problem or may be a sign of a significant and life threatening problem. People with atrial fibrillation are exposed to things such as fainting, congestive heart failure, and stroke. Paroxymal refers to patients with symptoms that resolve in less than (7) days and persistent to patients with symptoms resolving in over (7) days.

The drug, Multaq, was prescribed in particular for patients with severe heart disease, including those who were elderly, had other serious medical conditions such as hypertension or diabetes, a history of a previous stroke or cerebrovascular accident, or had evidence of serious heart disease or heart failure based up on their EKG and echocardiogram findings. The drug carries a “black box warning” (the strongest level of warning on a prescription drug) informing physicians that Multaq should not be prescribed for patients with severe congestive heart failure because of  concerns that use of the drug might worsen patients’ heart failure symptoms or increase their chances of dying.

Here is just a glimpse into the questionable history of Multaq:

• July 1, 2009 – Multaq, (dronedarone hydrochloride), was approved by the FDA for sale in the United States.  The drug was subject to a Risk Evaluation and Mitigation Strategy (REMS), which essentially means that the drug had been identified as one that would require special care in its prescription and use. As such, it was accompanied by special patient materials and warning labels not distributed with other drugs that are evaluated as posing less risk to patients.
• Early 2010 – FDA warned of possible problems with congestive heart failure in patients taking Multaq.
• Spring 2010 – FDA warned of a possible link between Multaq and a potentially fatal ventricular arrhythmia known as torsades de pointes.  Other drugs, such as Propulsid, have been recalled due to links to this same life-threatening arrhythmia as well as an electrical conduction problem in the heart known as “long QT syndrome.”
• September 2010 – FDA includes Multaq in a report entitled “Potential Signals of Serious Risks/New Safety Information Indentified by Adverse Event Reporting System (AERS) between July – September 2010,” which was part of a new initiative by the FDA to alert the public and medical community about potential, emerging drug-related safety issues.  This same report included some other drugs that remain under a cloud of suspicion and/or are the subject of current litigation efforts, including Epogen and Procrit (possible contamination with lamellae); Gemzar (liver toxicity); Keppra (linked to Stevens Johnson Syndrome and Toxic Epidermal Necrolysis); and Actos (rhabdomyolysis).
• January 14, 2011 – The FDA issued a Drug Safety Communication directed to patients and healthcare professionals regarding its receipt of numerous adverse event reports (also known as AERs) relating to liver toxicity, serious liver injuries, and acute liver failure requiring a liver transplant in patients taking Multaq.  At that time, it was estimated that more than 147,000 patients had taken the drug in the 18 months since it was approved.

Often, the potential for a new drug to cause liver failure is not identified until the drug is given to a large number of patients after the drug is placed on the market, and these patients, sadly, unknowingly serve as real world guinea pigs for new drugs that are tested on too few and under aggressively-controlled study protocol, such that study participants are often pulled from the pre-marketing clinical studies at the first signs of any toxicity and before it is possible to detect potential liver problems.  Drug-induced liver problems are a serious health issue in the United States, with more than 400 prescription and over-the-counter drugs being linked to hepatoxicity, with only a fraction of these drugs being recalled due to liver-related safety issues.

• February 11, 2011 – Drug warning label enhanced to include the risks of acute liver failure or hepatic toxicity.  The symptoms associated with acute liver failure include jaundice, abdominal pain, dark urine, itching, fever, malaise, anorexia, vomiting, and nausea.  Patients may also have abnormal blood tests slowing elevated liver enzymes.
• March 11, 2011 – Drug warning label further changed to discuss the potential for drug interactions, especially with warfarin (also known as Coumadin).
• June 21, 2011 – Multaq’s warning label was changed yet again to note that some patients who had taken the drug had developed serious pulmonary and respiratory problems, including interstitial lung disease, pneumonitis, and pulmonary fibrosis.  These serious lung problems had not been noted in the limited clinical trials completed to evaluate the safety of Multaq prior to FDA approval.
• July 21, 2011 – The FDA issued a “Drug Safety Communication” to doctors and patients regarding the increased risk of death and serious cardiovascular adverse events noted in an ongoing clinical trial involving patients taking Multaq (or dronedarone) for permanent atrial fibrillation (an indication for use of the drug that had not yet been approved by the FDA).  This clinical study is known as the Permanent Atrial Fibrillation Outcome Study Using Dronedarone on Top of Standard Therapy (PALLAS) Study.  The July of 2011 safety alert indicated that from July of 2009 through June of 2011 approximately 241,000 patients had ingested Multaq.  At that time, patients were urged to consult with their physicians regarding whether they should discontinue the medication, and were encouraged to report adverse events to the FDA and Sanofi-Aventis.  Physicians were also urged not to prescribe Multaq to patients with permanent atrial fibrillation, an off-label use of the drug. At that time, the FDA indicated that the data showing potential safety issues in the PALLAS clinical trial was preliminary, and that the Agency would be conducting a more thorough review to determine whether the same increased risk of cardiovascular death or serious heart-related side effects noted in study patients with permanent atrial fibrillation might also be seen in patients taking Multaq for paroxysmal or persistent atrial fibrillation or atrial flutter, conditions for which the drug had been approved by the FDA in 2009.
• August 5, 2011 – The Food & Drug Administrator and the manufacturer of Multaq updated the “Risk Evaluation and Mitigation Strategy (REMS)” plan, in order to further outline efforts to be undertaken to provide better information to patients and prescribing physicians in hopes of preventing future injuries and death to patients using Multaq.  In addition, patients who have suffered serious adverse reactions were urged to report them to the Food & Drug Administration at 1-800-FDA-1088 or at www.fda.gov/medwatch.  Patients have also been cautioned to consult with their physicians prior to discontinuing Multaq, as there are serious potential side effects if patients abruptly stop taking this medication.
• August 22, 2011 – The warning label was again modified to reflect that patients may experience changes in their kidney function while taking Multaq.  Adverse event reports have noted that patients experienced elevations in their creatinine and blood urea nitrogen (BUN) levels while taking Multaq.
• September 22, 2011 – The European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP), the drug safety organization similar to the FDA that oversees drug safety in the European Union, met to discuss safety concerns over Multaq and whether the drug should continue to be prescribed in Europe.

In the past, the EMA has shown that it is more inclined to move swiftly to recall dangerous drugs and to put the welfare of patients before the interests of the pharmaceutical industry, unlike the FDA which has shown a tendency to move at a much slower pace while it studies safety issues relating to drugs (and, sadly, to give the drug manufacturers a few more months or years for last-ditch efforts to peddle unsafe pills).  The EMA committee recommended that use of Multaq be limited in light of evidence that the drug was associated with serious adverse effects on the liver, heart, and lungs.

Meanwhile, patients in the United States are faced, yet again, with a difficult situation.  So, what should Multaq patients do?  Patients should consult with their physician now and on a regular basis to determine whether continued use of Multaq, in the face of growing safety concerns, is warranted given their particular medical history and personal risk factors.

Patients should also urge the drug manufacturers and the FDA to be more proactive in removing dangerous drugs from the market rather than continuing to issue press releases and revised warning labels which, obviously, are failing to protect patients from drug-induced injuries.

For additional resources related to Multaq, please visit these sites:

Manufacturer’s web site

Medication Guide for Patients

REMS

July 2009 label

February 2011 label

March 2011 label

June 2011 label

August 2011 label

FDA summary memo regarding review of the new drug application for Multaq

FDA drug approval package

7/21/2011 Safety Alert

1/14/2011 Safety Alert

January 2011 – FDA podcast on liver toxicity

As depicted in the following video, over the years, cardiologists have relied upon invasive catheterization to diagnose cardiac-related blood flow problems and muscle wall damage. However, placing a catheter into blood vessels and guiding it into the heart is technique-sensitive, and is far more invasive and less diagnostic than the use of Positron Emission Tomography (PET).

This is true because instead of using a mechanical, wire-like catheter, cardiologists can inject a less intrusive “Rubidium-82 saline liquid” into patients’ blood vessels  The short span radioactive liquid (having a very short 76 second half life) then combines with the blood that usually flows through the blood vessels. The Rubidium-82 liquid, also called a tracer, acts just like potassium. Rubidium-82 substitutes itself in place of potassium in the cells.

If the physician injects a potassium analogue tracer into a patient, the patient’s heart muscle cells will absorb the tracer. Note that blood vessels carry the tracer to the heart muscle, but while the tracer disappears in the blood, it collects in the heart muscle, providing a sharp contrast when viewed via a PET scanner that can photograph the emitting radiation.

Several minutes after the Rubidium-82 tracer injection, a PET image will show a concentrated, retained tracer in the heart, which contrasts with the low activity in the blood (because newly circulating blood is carrying away the excess tracer).

Since Rubidium-82 has a relatively short, 76 second half-life, after six half-lives (450 seconds or 7.5 minutes), investigators treat the tracer as completely decayed  – because only a mere 1.6% of original radioactivity remains. This brevity of activity means that the tracer cannot be stored and transported between facilities. Instead, it must be produced on-site.

The usual way to produce tracers is by using an expensive cyclotron. Because the cyclotron is expensive and cumbersome, researchers investigated alternative ways to produce tracers with less expensive equipment that could be used on-site in the offices of cardiologists or other healthcare providers. The Cardiogen-82 Strontium-82 to Rubidium-82 generator, which General Electric manufactures and distributes for Bracco Diagnostics, Inc., is a relatively inexpensive piece of equipment that can produce Rubidium-82 from Strontium-82 (which has a longer half-life of 24 days). Strontium-82 is produced from Strontium-85 (having a half-life of about 65 days). Given the much longer half-lives, strontium isotopes would be too toxic for use as tracers in humans.

The CardioGen-82 generator employs a long tin oxide tube that contains the more toxic Strontium-82 (parent), and normal saline is pumped through the tin oxide tube, which results in the manufacture of the less toxic Rubidium-82 tracer. Of course, it is paramount that physicians prevent an occurrence called “breakthrough,” which happens when Strontium-82 is carried along with Rubidium-82 in the tracer liquid in larger than permissible amounts. Injecting Strontium along with Rubidium into a patient increases the risks of radiation poisoning.

The relatively short half-life of Rubidium-82 is both an advantage and a disadvantage. On the positive side, quick decay means shorter patient exposure to radiation. And, physicians can perform repeated PET scans every 10 minutes, because the radiation from the previous dose has disappeared by that time. However, fast decay shortens the maximum scan time and reduces the quality of the scans. That is the reason why on-site Rubidium-82 tracer manufacture and direct tracer injection into a patient, within a really brief period, is so necessary.

The information, above, makes it clear that both catheterization and Rubidium PET scanning have diagnostic pros and cons. While Rubidium PET is less mechanically invasive, and more diagnostic than catheterization, Rubidium PET is, nonetheless, invasive because of the use of radiation in patients and the complexity of technique required in order to use the product safely. If Strontium-82 were to break through during a procedure, it could be disastrous to a patient.

Wow, the federal regulatory agency, Federal trade Commission (FTC), has taken a firm stand on products that promise “a better way to a better butt”. The FTC has reached a settlement with shoemaker, Reebok, over its claims concerning the popular EasyTone shoes.

I must confess that until reading the article in The Washington Post, I had not heard of EasyTone shoes and the claims Reebok was making about them. Apparently both the claims and the advertising were something that hit home with consumers because Reebok reportedly sold over $500 million of them in 2010.

I wanted to do a little investigating since I had never seen any of the commercials for EasyTone or the shoes that make similar claims made by Skechers. Here is one of the commercials:

I can understand why the FTC would get so worked up about the claims if they are false. I mean assuming they do not do what they claim; we could have sagging all over America. What if you actually had to exercise? I mean its absolutely outrageous.

Okay, I agree that if any manufacturer makes a claim about a product and it is not true (although Reebok and Skecher claim theirs is true), they should have to pay a price for false advertising. In this case, the FTC settled with Reebok for $25 million; probably representing some fraction of their profit margin in a single year. That is significant and important – and, it is exactly what the Federal Trade Commission is in the business to do.

I guess my “tongue in cheek” reaction results from comparing the FTC nailing Reebok for sagging butts, while drug manufacturers play in advertising Shangri-La on a regular basis. Take a look at the Reebok ad again. See all the imagery and visual suggestion? Drug companies do exactly the same thing; except drug companies are selling drugs, not the newest “uplift” device.

Ask yourself, what does attractive, successful, professional women sitting in a very expensive bar, have to do with Yaz birth control medication? Or, what does Humira have to do with planting sun flowers? How does Vioxx really relate to walking down a beach to go fishing as the sun rises radiantly over the ocean?

Drug manufacturers spend billions every year trying to tell us about the latest disease and, oh yeah, sell us their latest cure for the latest disease. In 2005 alone drug companies spent over $58 billion for promotion of pharmaceutical drugs to consumers. Drugs consumers can not just go buy, but must get a prescription from their doctor in order to obtain them.

In 2005, drug companies only spent $32 billion on research. That is nearly 50% of what they spent on advertising and that is both a startling and telling statistic.

What are the priorities for Big Pharma? They need the latest, greatest disease so they can tell you about it, suggest you may have it and convince you that they have the answer for you. And, the pressure is on them, because they have to do all of this before the studies come out that tell us the latest cure is simply making people sicker, killing people or that it simply does not really work. The profit must be made before the truth is known.

Be sure that drug companies are in the profit business. Although I know there are plenty of well-intentioned scientists employed by Big Pharma companies who are interested in helping people, finding the great cure for the worst disease. But, at the end of the day, drug companies make decisions based from profit motives and their marketing departments drive decisions a whole lot more than their research and science departments.

So, I am happy that the FTC takes their job seriously and, if Reebok’s claims were untrue, I am happy that they were forced to pay some penalty.

But when will the Food & Drug Administration take some pages from the FTC’s playbook and start bringing down real regulation on drug company advertising to consumers. When will the FDA put a stop to advertising that dilutes drug complications, expands drug benefits and suggests to consumers that if they do not feel sick, maybe they should think about it a little more

I went back and took a look at many of the drug companies advertisements and I seem to have remembered seeing every one of them. The Reebok ad, though, is one I missed and, I am reasonably certain I would have remembered it.

Your blood needs to clot, but it is a delicate balance. Insufficient clotting leads to excessive bleeding and too much clotting leads to obstructed blood flow, pulmonary embolism and strokes.

So, it is understandable that the Food & Drug Administration became worried about reports that birth control medications containing drospirenone were causing excessive clotting in women taking them. The FDA decided to conduct a review of literature and investigate the potential risks associated with birth control drugs such as, Yasmin, Zarah, Syeda, Safyral, Ocella, Yaz, Loryna, Gianvi, and Beyaz.

The Food & Drug Administration has now reached some preliminary conclusions that would be disturbing to me if I were a woman taking these medications. The FDA believe s that the increased risk for blood clots, pulmonary embolism and stroke are around 1.5 times more in women taking the drugs than in women taking other types of similar medications for birth control.

The manufacturer of Yaz and Yasmin agreed with the FDA in 2010 to amend its labeling to alert users of the potential for venous thromboembolism (VTE), but also indicated the risk was no greater than with other oral contraceptive preparations.

There are really two central issues.

The study and investigation being conducted by the Food & Drug Administration is exactly the same evaluation which should have been conducted by the manufacturers of these drugs BEFORE they were placed on the market. Where were the manufacturers when these drugs were being evaluated through clinical testing? Were risks of VTE suppressed during clinical trials? Were all the data of clinical trials provided to the FDA at the time the drug was submitted for final approval?

When Bayer began producing its commercials for Yaz depicting young, successful, attractive women talking about the miracles of Yaz, did they know? When Bayer began pushing the envelope by trying to promote Yaz as a treatment for acne in young women, did they know about the increased risks of stroke? When Yaz commercials with their fun loving, balloon flying commercials tried to lure young women to Yaz, did Bayer know that each person faced a potential one and one half times greater risk they would develop a stroke or risk death as a result of a pulmonary embolus?

So, it is great that the FDA is now evaluating these dangers of medications like Yaz, Yasmin and Beyaz; but where were these investigations and studies when manufacturers were making billions of dollars through the sale of them to young women?

The evidence condemning Metal on Metal (MOM) implants continues to grow. In a recent announcement by the National Joint Registry for England and Wales (NJR), it was revealed that 30% of MOM implants manufactured by DePuy Orthopaedics, Inc., a division of Johnson & Johnson require removal and revision within six years of implantation. The industry standard is 15 years or more.

In its report, the NJR revealed that MOM hip devices experience “by far” the highest rate of revision including removal and replacement. NJR data indicates that these devices are failing at double or triple the rate of others at five years. In addition, the report indicates that as time passes, the failure rate increases when compared to other hip implants. The data also tell us that women fared worse than men.

This report follows DePuy and Johnson & Johnson’s recall of both its ASR XL Acetabular and ASR Hip Resurfacing systems in August of 2011. It appears the recall was warranted. At the time of the recall, the reported failure rate for these two systems was 13%. This new data suggests the failure rate was even higher at 17%. At six years the NJR reported that 29% or almost one third of these devices required revision. Even a lay person with no medical training should recognize that failure rate as staggering. It also calls into question how the company and regulators would fail to identify this problem before doctors started pounding these rods and cups into the hips of thousands of patients!

The sad truth is they didn’t. Even if the company did, it’s unclear what they would have done with the information. A DePuy “spokesperson” said in response to the reported 1/3 failure rate that it, “shouldn’t necessarily be taken as gospel.”

Unlike other consumer recalls, dealing with the problem is not as simple as taking your car into the dealership for repairs. These patients have the defective devices implanted in their bodies. Fixing the problem requires undergoing painful revision surgery. Doctors are on record saying that revision surgery is much more complicated than the original surgery and carries far more risks. Many are unsuccessful leaving the patient with permanent disabilities.

In addition to regulatory action in Europe, the FDA has ordered 21 manufacturers of MOM implants to carefully study the issue of whether patients with these implants are being poisoned by the release of metal shavings or debris that is cast off when the device fails. Studies of patients with MOM implants have reported abnormally high blood levels of Cobalt and Chromium which are potentially dangerous. The FDA is studying the long term effects of heavy metal poisoning in these patients.

Well I am neither a doctor nor a scientist; which may help explain why I am scratching my head in bewilderment after reading the latest article at msnbc.com.  The article sets forth an association between common household NSAID’S (non-steroidal anti-inflammatory drugs) with an elevated risk of miscarriages. You are familiar with the NSAID drugs, like Aleve and Ibuprofen that we are encouraged to use for headaches and other pain.

According to a study in the Canadian Medical Association Journal there is almost 2.5 times an increase in the risk of miscarriage while using these drugs. As the article states it’s no time to “freak out”, but it certainly seems like a time to take notice. The marketing machines behind some of these drugs portray that these over the counter medications are almost like taking a multivitamin. This study once again shows that things aren’t always as simple or benign as they are represented in drug company advertising.

Listen, if I do not take NSAID’s, obviously this one issue doesn’t directly affect my body, but I have a wife and 3 beautiful girls to worry about.

When I view this newest concern with recent Celebrex ads I’ve watched it has not left me with warm and fuzzy feelings for Big Pharma and their methods. When a product that was essentially pulled from the market place, like Celebrex, now in the “new roll out – take 2” mode,  comes out swinging with commercials that boast Celebrex essentially has the same exact cardiovascular risk factors as common household NSAIDS, I am left a little empty.  So over the counter NSAID’s are just as risky? Great, am I supposed to feel better about Celebrex or should I be a heck of a lot more concerned about existing over the counter NSAID products? For me, I continue to be confused….

I have also learned a lot more about NSAID’S and their role in causing Stevens-Johnson syndrome. According to Skin Association there are links to Stevens-Johnson syndrome, a potentially deadly skin disease that usually results from a drug reactions, and NSAID’S. Think of Stevens – Johnson syndrome as something that burns your skin from the inside out; ultimately resulting in 3^rd degree burns all over your body. It is painful and ultimately can be fatal – all the result of the way some drugs react.

I know, I know, it’s all very confusing. Should we trust these studies or “links” when they conflict with the ones that drug manufacturers set up?

Or even better, should it simply be a “buyer beware” in the arena of chemicals, compounds and drugs?

Should consumers be required to not only read the very tiny, tiny fine print on the drug labels, but also maintain sufficient chemical engineering acumen to truly understand them?

Plus, even if you read the scientific and legalese mumbo jumbo put out in the past there have been strong concerns that inadequate warnings have existed associating the NSAID’s with all of these issues. Considering these products are in the homes of almost every American, being used by the young, the old and yes, even those who are pregnant, should not more be done to properly warn the unsuspecting consumer?

Our modern times have created a hectic life and not everyone has the time to read complicated details in fine print stuffed in the bottom of discarded boxes. Not everyone reads scientific articles, which often require medical knowledge to understand them as a part for their work, as I do.

I think these various warnings should be delivered to all us consumers in a manner, at least equally effectively, if not more so than the slickly produced ads that run on TV and in print to sell drugs.

The last time I got an Advil coupon in my Sunday paper it wasn’t in tiny black and white print, folded up 15 times, and laying at the bottom of the newspaper sleeve to be easily discarded. It was in full color, large print and had pretty decorations – well, except the part about when it expired.

Since the 1980s, many have turned to medications such as Prozac to combat their depression.  However, those who are pregnant or attempting to get pregnant need to think again before taking these drugs.  In fact, Prozac, when taken during pregnancy, has resulted in many birth defects, some of which include limb defects, craniosynostosis, anal atresia, persistent pulmonary hypertension of the newborn (PPHN), omphalocele, heart defects, and neural tube birth defects.

On July 19, 2006, the FDA released a warning that SSRI antidepressants can cause serious or life-threatening lung problems in newborns whose mothers took the medication while pregnant. The warning came after a study was published in the New England Journal of Medicine that showed infants were six times more likely to suffer Persistent Pulmonary Hypertension in the Newborn (PPHN) after being exposed to SSRIs, the class of drugs that includes Prozac, Paxil, Celexa, Effexor, Lexapro, Pristiq, and Zoloft.   Babies whose mothers took Prozac and other antidepressant drugs in this class while pregnant may also suffer withdrawal symptoms such as agitation, poor feeding, and insomnia.

Prozac (also known as fluoxetine) is a selective serotonin reuptake inhibitor (SSRI) antidepressant. Prozac affects chemicals in the brain that may become unbalanced and cause depression, panic, anxiety, or obsessive-compulsive symptoms.  In the early 1970s, evidence of the role of serotonin in depression began to emerge, and the hypothesis that enhancing 5-HT neurotransmission would be a helpful way to combat depression was put forward.  On the basis of this hypothesis, efforts to develop agents that inhibit the uptake of 5-HT were initiated. These studies led to the discovery and development of Prozac, which was approved for the treatment of depression by the FDA in 1987.

Prozac has been manufactured and marketed by Eli Lilly & Company, which is based in Indianapolis, Indiana.  However, on August 2, 2011, Lily’s patent for this profitable drug expired.  This has resulted in an estimated loss of  $2.4 billion in annual sales for Lilly.   The patent was invalidated after a lengthy legal battle waged by a small, aggressive generic-drug company called Barr Laboratories.  The loss of this patent lawsuit by Lilly will allow other companies that want to sell the drug to be able to do so.  Now, a 20-milligram capsule that presently retails for $2.50 likely will fall to less than 25 cents per capsule.  This will significantly affect Lilly’s revenues, which were reported during the 2010 fiscal year to be $23 billion in total sales and $5 billion in net income.  Since it was launched in early 1988, Prozac has been one of the biggest-selling drugs in history; its $21 billion in sales represents about 30% of Lilly’s revenues in that period.  Lilly is also the manufacturer of other well-known psychiatric drugs, including  Cymbalta and Zyprexa.

It is unclear at this time how this change in the patent protection for Prozac will affect some of the pending and upcoming litigation being filed on behalf of children who have suffered devastating birth defects as a result of their mother’s ingestion of this drug during the first trimester of their pregnancies.  Nonetheless, the drug is still being prescribed and children are still being born with birth defects.

It is important that patients obtain the facts about antidepressants and use of the drugs during pregnancy.  It is also important that patients understand what remains unknown about the potential safety risks that Prozac and other drugs pose to a developing fetus, facts that would be shocking to most patients especially since the drugs have been marketed for more than 20 years!  Most importantly, speak with your doctor before doing anything, especially before getting off the medication, as it is very important that patients be properly weaned from antidepressants and that other supportive therapy be administered to manage the depression.

Big Tobacco is not only finding it hot in the great State of Florida, but also in the great State of Connecticut as well.

There, a federal court judge, Hon. Stefan Underhill, was asked by RJ Reynolds to overturn a jury verdict for the plaintiff in the amount of $28 million (Izzarelli v. RJ Reynolds Tobacco Co; case no. 3:99-cv-2338). Judge Underhill apparently did not buy what Big Tobacco was selling any more than the jury did.

Santa Smokes So It Must Be Good

This new Connecticut case is interesting in a few ways. Big Tobacco brought on its typical defenses of cigarettes are not addictive, but if they are addictive, the plaintiff could have quit if she really tried; that there were warnings about the dangers of smoking on the cigarette packages, if they are dangerous; and that if cigarettes are dangerous, they only are because of the ingredients that are naturally found in tobacco.

The court set forth a number of things brought into evidence in the case that justified the jury verdict of $28 million.

During the 1970’s, RJ Reynolds was losing market share in the new smoker group and was desirous of catching up with their competitors in the ability to addict people to cigarettes. They had known for a very long time that a cigarette is really nothing more than a delivery system for nicotine in a form that is acceptable to the user. In other words, Big Tobacco could sell something that allowed the user to inject the drug nicotine into their system through a cigarette much easier than they could by selling it in hypodermic needles. Big Tobacco had also known for quite some time that it is “free nicotine” that really gives the smoker the “kick” of nicotine into the system and, more importantly, Big Tobacco knew they could control the levels of “free nicotine” in cigarettes, thus controlling the “kick”.

What RJ Reynolds and the other manufacturers really craved for was to lure potential smokers under the age of 18 into the cigarette addicted population. Sadly for RJ Reynolds, Kool cigarettes, manufactured by Phillip Morris, had been burning them on market share. RJ Reynolds quickly undertook to fix this problem through manipulation of nicotine in their product:

“Notably, R.J.Reynolds discovered that (when altered with fructose alone or a fructose/ammonia gas mixture) the tobacco blend formulation G7 used in its Winston and Salem products increased the amount of nicotine in the cigarette as well as the percentage of nicotine transferred to the smoker.”

And:

“With respect to the effective dose range of nicotine required to maintain addiction, R.J. Reynolds understood that, although an increase in free nicotine would enhance the addictive property of the cigarette, a decrease in the nicotine yield of the cigarette would increase the number of cigarettes required to meet the addiction demand.”

“…the jury could have reasonably found that R.J. Reynolds manipulated and altered the tobacco and the chemical additives in Salem Kings to enhance the addictive nature of the product, increase the number of cigarettes smoked by the consumer, and ultimately deliver a higher level of carcinogens to the consumer as compared to other cigarette products.”

The evidence in this case set forth that not only were Big Tobacco targeting teens in hopes of adding them to the addicted masses, for 20 years after the plaintiff (Izzarelli) began smoking and as late as the mid-1990’s, Big Tobacco persisted in its efforts to “dispel the notion that cigarettes are an addictive product and to discredit health warnings about cigarettes maintain the dangers of cigarette smoking have been well known for a century, while testifying under oath that the claimed dangers of their products do not exist at all.

In Florida, Big Tobacco regularly stands before juries and tells them the same lies that their own CEO’s have previously testified about under oath. Tobacco company lawyers stand before juries and tell them all about how the dangers of smoking cigarettes have been known to everyone for ever. They claim that nicotine, although addictive, is a naturally occurring ingredient in tobacco that is, well, not THAT addictive. They tell jurors all about “free will” and that, well shucks, they are just a bunch of poor farmers trying to eke out a living.

The truth is Big Tobacco has taken a natural product (tobacco) and spent billions of dollars trying to re-engineer it into the “best drug delivery system in the world”, while they tinker with the addictive ingredients of their product to try and increase market share. All the while Big Tobacco has been telling the public things like this excerpt of a 1976 letter from Public Relations employee TK Cahill:

Big Tobacco's Script

The truth is that Tobacco companies want the public to believe its version of revised history. Big Tobacco needs the public and juries to believe they did not manipulate cigarettes to increase addictiveness and that anyone can quit anytime they want; they need them to believe the industry did not spend billions of dollars trying to convince the public that cigarettes were not just safe, but actually healthy for you; and they need them to believe that smokers who started smoking back in the 1940’s and 1950’s knew about the dangers of smoking.

In sum, Big Tobacco is still selling poison. They still have cigarettes on the market that addict and kill people every day. Now, though, they are also selling lies, fiction and fables to jurors and the public; well, at least to those who do not remember anything but Tobacco’s revisionist history.

On August 25, 2011, Public Citizen, a consumer safety organization founded by Ralph Nader decades ago, submitted a Consumer Petition to the Food & Drug Administration seeking a ban of transvaginal surgical mesh products that are utilized in surgeries to repair pelvic organ prolapse.  The petition was signed by Dr. Michael Carome, Deputy Director, and Dr. Sidney Wolfe, Director, of Public Citizen’s Health Research Group and Dr. Daniel Elliott, Assistant Professor of Urology, College of Medicine, and Mayo Clinic.

Pelvic organ prolapse is a common condition in women that occurs due to weakness in the tissues and muscles that support the bladder, uterus, and bowel.  There are a number of conservative as well as surgical treatments for these conditions (such as anterior or posterior colporrhaphy) that do not involve the implantation of a foreign body.  Most of the products that are being questioned are manufactured with non-absorbable synthetic polypropylene; a product that many physicians mistakenly believe (based upon representations by device manufacturers and outdated science) is inert once placed into the body.

The petition indicates that nearly 300,000 surgeries for pelvic organ prolapse were performed in 2010 in the United States, and that 70,000 of these surgeries utilized a transvaginal surgical mesh or sling product.  This statistic is particularly troubling since the FDA first sounded the alarm about potential safety issues with this entire class of devices in 2008, yet very few patients and surgeons seem aware.   The FDA’s alert on October 20, 2008, came many years after others first raised the very questionable safety record, troubling regulatory approval history, and scant data to support efficacy for these products.  An analysis of adverse event reports by the FDA from 2005 through 2008 indicated that the Agency had received more than 1,000 reports of complications associated with use of transvaginal mesh in surgeries in patients who had experienced pelvic organ prolapse or urinary incontinence.   A July 13, 2011, revised safety alert from the FDA indicated that the MAUDE database utilized by the Agency for adverse event reports included nearly 4,000 reports of injury, death or device malfunctions between 2005 and 2010, with the number of new AER reports growing exponentially (a 500% increase) over the past few years.

In urging a recall of the products, Public Citizen reviews the scientific literature that has been published since the products were first introduced in the United States many years ago.  Some studies show that patients tend to have less recurrence of pelvic organ prolapse after placement of the synthetic polypropylene devices; however, those findings alone do not justify use of these unsafe products. Most of the published scientific studies had limitations in their persuasiveness, especially since they were short-term studies, involved a limited number of patients, did not include controls, were not “blinded” to avoid bias, were not designed to evaluate safety issues, etc.  The published medical literature also shows that patients who have been implanted with transvaginal surgical mesh are suffering a number of complications, most of which are not associated with other surgical and non-surgical treatment options for pelvic organ prolapse.  These serious side effects associated with the mesh products include:  mesh erosion through the vaginal wall in 5% to 19% of patients; development of urinary incontinence; bladder perforations; pelvic hematomas; significant blood loss and post-operative complications; chronic infections; sexual dysfunction; scarring, tightening, and shrinkage of the vagina; chronic pain; urogenital fistulae formation; and the need for multiple additional surgical procedures due to mesh-related complications.

The transvaginal mesh products targeted by this Consumer Petition have been subject to litigation efforts for more than a decade, and have been on an FDA “watch list” for nearly three years.  The ban urged by Public Citizen is one that should have been instituted years ago, but, instead, the device manufacturers have continued to aggressively market these devices to unsuspecting patients while the overworked and underfunded FDA reviews mounting data showing that the devices subject patients to serious risk of injuries or death while providing little or no benefits.  The consumer organization also seeks a recall of products, and that any similar devices in the future undergo far more rigorous testing prior to being approved for marketing, including the suggestion that the products be re-categorized from Class II to Class III devices under the FDA regulations.  The current problems with the emergence of defects in these mesh devices once they are implanted into patients stems, in part, from the improper categorization of the devices in class II coupled with an abbreviated 510k approval process, which permitted them to be approved for sale and implantation with only the most rudimentary tests and did not require thorough testing to confirm that the materials utilized were truly biocompatible.  Examples of other class II devices include powered wheelchairs, infusion pumps, and surgical drapes. Unfortunately, little was known about how these devices would perform once they were implanted in women, as very little was done in the way of clinical studies and trials in humans prior to approval for marketing.  It is inexcusable that hundreds of thousands of women have become guinea pigs for these inadequately-tested devices.

This petition extends to a number of transvaginal surgical mesh products that are sold in the United States by Ethicon (a division of Johnson & Johnson), American Medical System, Boston Scientific Corp., C.R. Bard, and Proxy Biomedical.  The products for which Public Citizen requests a marketing ban and/or recall, includes:

• Gynecare Prolift Total, Anterior and Posterior Pelvic Floor Repair Systems (manufactured by Ethicon, Inc. of Somerville, New Jersey)
• Gynecare Prolift +M Total, Anterior, and Posterior Pelvic Floor Repair Systems (Ethicon, Inc.)
• Gynemesh Prolene Soft Nonabsorbable Synthetic (Ethicon, Inc.)
• AMS Elevate Anterior and Apical Prolapse Repair System (American Medical Systems, Inc., headquartered in Minnetonka, Minnesota)
• Pinnacle Pelvic Floor Repair Kits (Boston Scientific Corp., based in Marlborough, Massachusetts)
• Avaulta Support System (C.R. Bard, Inc. of Covington, Georgia)
• Polyform Synthetic Mesh (Proxy Biomedical, Ltd., baed in Galway, Ireland)

The facts regarding transvaginal mesh, as laid out in Public Citizen’s petition and talking points, are quite simple:

• “Use of surgical mesh for transvaginal POP repair provide no clinically significant benefit compared to repair without mesh using only native tissues”
• “Safety assessment:  the use of surgical mesh for transvaginal POP repair commonly causes serious complications”
• “Given the absence of evidence for clinically significant benefit and the overwhelming evidence of very serious, common risks, use of synthetic surgical mesh products for transvaginal repair of POP is not ethically justifiable”
• “Despite a complete lack of clinical data demonstrating that these mesh devices were reasonably safe and effective for transvaginal repair of POP, these devices have been heavily promoted by industry and their highly paid physician consultants.  As a result, tens of thousands of women have been seriously harmed, many permanently”
• “Commercial interests related to surgical mesh kits for POP repair have taken precedence over patient safety and welfare”

So, what next?  One can only hope that the FDA will soon stop sifting through study after study and the stacks of adverse event reports, and move quickly to grant Public Citizen’s petition and pull these products from the market, or, although somewhat of a fantasy, that the device manufacturers would withdraw the products on their own.  The reality, however, is that the FDA is far more prone to warn, and warn, and warn again about safety issues, and leave it to patients and physicians to sift through all of the conflicting information from consumer, patient and legal advocates versus those who seek to defend these products and hope that patients make the correct decision.  I hope so too, as that is not an easy task, and is a decision that is fraught with problems if it is made poorly.

Additional Resources

August 2011 – FDA:  Continuing Concerns Relating to Transvaginal Mesh

August 2011 – Informed Decisions and the Use of Surgical Mesh

August 2010 – Mentor ObTape Vaginal Ling Overview

October 2009 – ProteGen Sling:  Overview

May 2009 – Suffering in Silence From a Medical Device – Surgical Mesh (Part 4)

April 2009 – Suffering in Silence From a Medical Device – Surgical Mesh (Part 3)

April 2009 – Suffering in Silence From a Medical Device – Surgical Mesh (Part 2)

March 2009 – Suffering in Silence From a Medical Device – Surgical Mesh (Part 1)

February 2009 – Curing Incontinence May Cause Greater Harm

December 2008 – The FDA’s Approval of ProteGen Baffles the Mind

November 2008 – The FDA Transvaginal Surgical Mesh Placement Complications Notification:  Manufacturer Identification and MAUDE Report Breakdown by Device

November 2008 – Mentor ObTape Litigation Expands

November 2008 – Tension Free Vaginal Tape (TVT or Vaginal Sling):  What is it and how is it placed?

October 2008 – Under the RADAR and Over to Market:  FDA 510(k) Submissions for Today’s Vaginal Slings are based on an FDA Equivalent Device That Was Actually Defective

August 2008 – Something Doesn’t Mesh

If life weren’t difficult enough for depression sufferers, now there’s more to worry about.

The FDA recently alerted psychiatrists and cardiologists that Celexa (Citalopram) has been linked to potentially fatal cardiac arrhythmias. Those taking doses more than 40mg. were at increased risk of developing Torsade de Pointes syndrome which can be fatal.

Torsade de Pointes is a change in electrical activity of the heart which leads to elongation of the QT interval on electrocardiogram. The FDA announced that in addition to those taking over 40mg. of Celexa, those with pre-existing heart conditions and those with low levels of potassium and magnesium in their blood were also at increased risk.

The danger of Celexa related cardiac rhythm abnormalities goes far beyond just those taking Celexa for depression. Celexa has been prescribed for other “off label” conditions such as:

• Anxiety
• Panic disorder
• PMDD (pre-menstrual dysphoric disorder)
• Body dysmorphic disorder
• OCD (obsessive/compulsive disorder)

It would appear those taking the drug for these reasons would similarly be exposed to the risk.

Celexa is in the class of drugs known as SSRI’s or selective serotonin reuptake inhibitors that have recently been linked to birth defects when pregnant mothers take the drug early in pregnancy.

As with many anti-depressants, Celexa also carries a black box warning of the risk of suicidal thinking and behavior in those under the age of 24 who take the drug.

The FDA recommended that Celexa and its generic equivalent (citalopram) should not be prescribed in doses above 40mg. It also warned against prescribing the drug to patients with heart rhythm disorders or metabolic disorders such as hypokalemia or hypomagnesemia (low potassium or magnesium).

Alerts such as these should cause the consuming public to ask why the manufacturer of this medication did not know of this risk prior to putting the drug on the market? Likewise, since the drug has been on the market since 1989, why is this just coming to light? It should also highlight the inadequacy of generic manufacturers’ slip-shod post market surveillance. Why is it the FDA has to uncover these risks? A responsible manufacturer, monitoring adverse event reports should be the one bringing this to light.