Incomplete Crestor Side Effects: Diabetes Risks

JUPITER Study on Crestor Ignored Documented Diabetes Risks

Cholesterol lowering drugs called Statins are currently very popular and big sellers for large pharmaceutical companies.  AstraZeneca’s drug Crestor (Rosuvastatin) in particular, is billed as a blockbuster “wonder drug” and is now a $2Billion seller.  A recent JUPITER drug study (Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin) published in The New England Journal of Medicine heavily promoted the benefits of Crestor.

The medical researchers in this study claimed that when patients with no pre-existing cardiovascular disease and normal LDL cholesterol numbers, but with elevated C-reactive protein – CRP (a marker of blood vessel inflammation which may be a sign of cardiovascular disease), were administered 20 mg of Crestor each day, that it greatly reduced their risk for a major cardiovascular event such as heart attack or stroke. 

In other words, according to the study, Crestor, a cholesterol-lowering drug, was promoted as having health benefits when prescribed to people who, other than somewhat elevated CRP levels, were healthy, didn’t have high cholesterol and also had no other chronic conditions. 

As strange as it may seem now, the media immediately embraced the concept and the drug Crestor.  A star was born.

Bending Crestor Benefit and Side Effect Stats

Glowing published reports stated that Crestor reduced the combined risk of heart attack or stroke in the higher-CRP population by 47%, reduced the risk of heart attack by 54%, cut the risk of stroke by 48%, and even lowered the total mortality rate by 20%. 

Impressive at first look, but the main problem with the media accounts was that the media coverage of the JUPITER Study ignored some of its major oversights and significant problems, oddly enough, in a way the benefitted AstraZeneca, the company that funded the entire study and that also manufactures and markets Crestor.

One glaring omission according to the JUPITER Study’s own statistics was that, while the number of heart attacks went down in the Crestor group, the total number of fatal heart attacks went up 50% in the Crestor group, when compared to the placebo group.  This significant point somehow never made it into media accounts of Crestor’s “wonder drug” status.

The JUPITER study results, published in the New England Journal of Medicine, also contain at least three major areas of potential bias:

1.) The entire study was funded by AstraZeneca, the pharmaceutical company that makes and sells Crestor.

2.) The lead researcher on the JUPITER Study is listed as a co-inventor on Crestor patents related to the test for elevated levels of high-sensitivity C-reactive protein, which the study puts forth as a strong indicator for initiating statin use.

3.) The vast majority of the researchers, doctors and other professionals conducting the JUPITER Study, and listed in the citations at the end of the study, were financially sponsored, supported or retained by a veritable “who’s who” of global pharmaceutical companies, including AstraZeneca.

An intelligent person can draw their own conclusions about the objectivity and unbiased nature of such a study, given the above points.

When one looks closely at the study numbers, many seem to only emphasize Crestor’s positive effects, while ignoring its significant negative side effects. According to the study, Crestor cut the risk of a cardiac event (meaning myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina or death from cardiovascular causes) nearly in half (actually 44%)  for the Crestor group of patients in the study.  Sounds good, but it is not the complete story.

Over the two-year (1.9 year) study, 0.77% of the Crestor study group experienced a cardiac event, compared with 1.36% in the placebo study group. According to the study’s own findings, 120 patients would need to take this very expensive drug for almost two full years in order for a single patient to benefit from Crestor. The risk of taking any prescription drug with known side effects is never to be taken lightly, but in this case with the benefits being cited as so tiny, it makes it very hard to justify taking such an expensive drug without a very compelling reason.

Risk of Diabetes Associated with Use of Crestor

Other than the many known side effects of Crestor, the JUPITER Study actually found and documented another significant and dangerous side effect – diabetes. Media accounts of this ”wonder drug” overlooked that physicians reported a full 9% increase in the incidence of diabetes within the Crestor group.  In the study, 270 Crestor group patients developed diabetes over the course of the two year trial, while only 216 placebo group patients developed any form of diabetes. On the web site MedicationSense.com, Jay S. Cohen, MD, author of What You Must Know About Statin Drugs and Their Natural Alternatives, wrote, in a criticism of the JUPITER Study:

“Imagine taking Crestor to prevent a heart attack and getting diabetes instead, which greatly increases the risks of heart attack and stroke.”

A strong consensus exists that until there are more independent follow-up studies to prove that the “wonder drug” claims of Crestor are true and that it is safe, the public must resist being a victim of aggressive marketing efforts by companies like AstraZeneca, or even by their own doctors.  A patient must learn everything that they can about every option at their disposal, and then work with doctors and other health professionals that they trust, to make the best and most informed choices possible regarding their own health.

Contact a Crestor Lawyer about a Crestor Diabetes Lawsuit

If you or a loved one took the cholesterol drug Crestor (Rosuvastatin) and developed diabetes, heart failure, or a stroke please contact a Crestor Diabetes Lawsuit Attorney at our law firm immediately. It may be too late to recover from some the devastating effects of Crestor, but an experienced pharmaceutical products liability lawyer at the Willis Law Firm can assist you in legal action against AstraZeneca, the maker of this dangerous drug. You are not alone. Join other Crestor victims and their families in speaking up and fighting for your legal rights.

Please fill out our free online legal evaluation form and we will contact you within 24 hours, or call our offices at 1-800-883-9858 for immediate help. Please keep in mind that certain states have statutes of limitation that limit the amount of time you have to file a lawsuit or seek legal action. Contact our law firm immediately so that we may explain the rights and options available to you and your family.

Doctors Placing Millions of Patients on Powerful, Cholesterol Drug Crestor

A recent Crestor study was published in The New England Journal of Medicine that involved more than 17,000 subjects and examined the Crestor’s effectiveness in reducing elevated blood levels of C-reactive protein (CRP), a suspected marker for cardiovascular disease. It is generally accepted at the present time that an increased level of inflammation is associated with a higher incidence of heart attacks and strokes.

In the Crestor-CRP study, the authors reported that over an almost two year study, there was a 44% reduction in cardiac events (defined by the study as heart attack, stroke, severe angina, or cardiac death) among the subjects in the Crestor group versus those in the placebo group.  A 44% reduction sounds impressive, but in this case, it is very misleading.

At closer examination of the study results, over the 2 year study, 1.36% of subjects in the placebo group experienced a cardiac event and 0.77% of subjects in the Crestor group experienced an event. The true difference was 0.59%. That is, less than 1%, which is a miniscule difference.

In fact, the difference was so tiny that it would require 120 individuals with elevated CRP taking Crestor every day for two years in order for just one person to possibly obtain that benefit. Meanwhile, the other 119 individuals taking and paying for Crestor for the same two years would obtain no protection from any of the listed cardiovascular events, and would be exposing themselves to a host of other known potential Crestor and statin side effects, as well as other potentially serious complications.

Why push the Crestor-CRP study results so loudly inspite of them being so tiny?

The truth of the matter is that the Crestor-CRP study was underwritten by AstraZeneca, the manufacturer of Crestor. It has been seen over and over that the marketing divisions of large pharmaceutical companies are true experts at generating the maximum amount coverage by the commercial media for their studies, even if any actual results are minimal or unimpressive, as is clearly the case in the Crestor-CRP study. As is true in most advertising campaigns of this type, vast exposure means greater sales and huge profits.

In only one case did a major news media outlet offer a dissenting opinion. In “Doctor Urges Caution in Interpreting New Findings on Cholesterol Drug,” Dr. Nortin Hadler of ABCNEWS.com wrote, “The benefit shown in this study is tiny, and if [the Crestor-CRP study] were repeated, there might be no benefit at all. I never leap to act on the basis of such small effects.”

Crestor-CRP Study: Serious Crestor Diabetes Side Effects Downplayed  

In the Crestor-CRP study, the drug displayed many of the most common negative side effects of other statin medications. The side effects of this types of statin drug includes abdominal pain, muscle pain, severe muscle breakdown (rhabdomyolysis), kidney failure, and liver failure. Study subjects in the Crestor group experienced these side effects more often than subjects in the placebo group.

A far more serious adverse effect occurred with Crestor: 270 cases of newly diagnosed diabetes were reported among Crestor users, and 216 cases were reported among placebo users. The 54 additional cases of diabetes in the Crestor group was a significant and worrisome finding. Diabetes is one of the most destructive, life-shortening disorders of our time. It also is a leading cause of heart attacks and strokes.

Imagine Taking Crestor to Lower Cholesterol and Prevent a Heart Attack but Getting Diabetes Instead

When the FDA evaluates a new drug for approval, it must make a decision based on whether the particular drug will produce significantly more benefit than risk of harm. Based the negative results in the Crestor-CRP study associating it so strongly with many new cases of diabetes. Because of the strongly negative results in the Crestor-CRP study associating it with so many new cases of diabetes, many professionals believe that if it were being evaluated today for approval by the FDA,  Crestor would not be approved.

Speak to a Crestor Lawyer about a Crestor Diabetes Lawsuit

If you or a loved one took the cholesterol drug Crestor (Rosuvastatin) and developed diabetes, heart failure, or a stroke please contact a Crestor Diabetes Lawsuit Attorney at our law firm immediately. It may be too late to recover from some the devastating effects of Crestor, but an experienced pharmaceutical products liability lawyer at the Willis Law Firm can assist you in legal action against AstraZeneca, the maker of this dangerous drug. You are not alone. Join other Crestor victims and their families in speaking up and fighting for your legal rights.

Please fill out our free online legal evaluation form and we will contact you within 24 hours, or call our offices at 1-800-883-9858 for immediate help. Please keep in mind that certain states have statutes of limitation that limit the amount of time you have to file a lawsuit or seek legal action. Contact our law firm immediately so that we may explain the rights and options available to you and your family.

Should You be Taking Crestor? What the Crestor Study Really Found.

A recent study was conducted and reported to the media as proving that just about everyone should be taking Crestor because of the way it lowered the incidence of stroke and heart attack.

As usual, when we read the actual study, we find that it said something very different.

The entire study as published in The New England Journal of Medicine is available for free :

“Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein”

Here is a brief summary of how the study was conducted:

The researchers found a group of men over 50 and women over 60 years old who had normal cholesterol but whose C-reactive protein was elevated. C-reactive protein believed to be a marker for inflammation, particularly inflammation in your arteries.

Take a look here to see the other characteristics of the participants in this study:

Baseline Characteristics of the Crestor Study Group

Several things leap out that were not made clear in the popular press reporting of this study.

• First of all, they were older people. The median age was 66. Secondly, though they had normal cholesterol they had other significant risk factors for heart disease and stroke:
• They were overweight. The median BMI was 28.3. That would translate into a weight of 165 lbs for the average 5′ 4″ woman or 192 lbs for the average 5′ 9″ male.
• More importantly, they had higher than normal blood sugars. The median A1c was 5.7% which I have been told by an endocrinologist is high enough to suggest undiagnosed diabetes.
• The interquartile range(a measure of the area in which most values concentrate) for this study group was 5.4% – 5.9%. These figures alone tell us that these people had a higher than normal risk of heart attack since several large studies have shown that the risk of heart attack rises in lock step with the rise of A1c as it goes over 4.7%. At 5.7% the risk is already significantly higher than at true normal.
• Finally, These people had elevated blood pressure–which is another well known pointer to early heart disease. The median blood pressure was 134/80. Doctors now believe 120/80 is the upper bound of normal.

You need to also look at who was excluded from the study:

• Women taking hormone replacement therapy,
• People with any indicator of liver or kidney abnormality,
• People with high blood pressure,
• People with thyroid disease,
• People with autoimmune disease and
• People with a history of alcoholism or drug abuse.

So, why were these people excluded from the study? 

These people were excluded because, among other things, earlier studies have shown that:  Crestor might be very dangerous for them.

Will these same people be excluded from the patients to whom Crestor is prescribed?  Probably not.

The remaining study participants were then put on Crestor, a newer and very expensive statin drug. Note that the study was run exclusively by people with strong financial links to the company that makes Crestor. (More about this at the bottom of this article.)

After two years the study was stopped because it found that people in this group taking Crestor had about half the risk of “end points” than people taking a placebo. These “end points” included were fatal and non fatal myocardial infarction [heart attack], fatal and nonfatal stroke, arterial revascularization [putting in a stent], hospitalization for unstable angina, or confirmed death from cardiovascular causes.

But lets look a bit closer at the statistics. Whenever anyone uses the “Risk” statistic, you can be sure they are trying to amplify a very small statistic into a larger one. Here’s what the actual statistics came up with: There were a total of 393 “end points” reported among the 17,802 people involved in the study. There were a grand total of 109 more “end points” among the people taking placebo compared to those taking Crestor.

In this group of 17,802 people involved in the study, half of whom were taking Crestor, there were 99 heart attacks or 5 per 1,000. Of these 15 were fatal or 8 in 10,000. There were 97 strokes of which 9 were fatal, a rate of 5 in 10,000. These numbers are for the group as a whole.

The most frequent endpoint was getting a stent put in, which occurred in 202 cases or about 1% of the group. When considering this statistic, note that Dr. Davis the cardiologist who writes the Heart Scan Blog believes that this procedure is dramatically overused because there is a strong economic motivator involved: this kind of procedure is the primary way that cardiologists make a living.

It is also worth noting that the way these statistics were collected one person may be recorded as having several “end points” though in fact they had only one incident or hospitalization. In fact, it is worth noting that the way that these end points are reported is so confusing, with so much overlap that it is very hard to know exactly what is being reported. The total given for “primary end points” is much lower than the total of all the various end points listed.

So right away it is important to note that the actual likelihood of death or stroke in this group of middle aged people with clear cardiovascular risk factors, while always regrettable, was still actually quite small.

But no one wants to experience any of these “end points.” So let’s look more closely at what happened when people took 20 mg of Crestor every day for two years.

Though the way the data was reported was carefully arranged to obscure this finding, it appears that while there were indeed slightly less than half as many heart attacks within the group taking Crestor, there were 50% more fatal heart attacks in the group taking Crestor.

The way that this is reported is thus:

Nonfatal myocardial infarction: Crestor 22 Placebo 62
Any myocardial infarction: Crestor 31 Placebo 68

Subtract “Nonfatal myocardial infarctions” from “Any myocardial infarctions” and you get Fatal Myocardial infarctions, a statistic which is NOT reported in the list of “end points.” But simple math gives us the information that there were 9 fatals in the Crestor group as opposed to 6 in the placebo group. That is a 50% higher rate for fatal heart attacks in the Crestor group.

Okay, so it looks like taking Crestor cut down the incidence of heart attack by 37 cases, but did not cut down on the deaths from heart attack. In fact, the proportion of heart attacks that were fatal in the Crestor group was 29% compared to 9% that were fatal in the placebo group.

Why is this not noted by the authors of the study?

In total there were 49 more deaths from any cause in the group taking placebo than in the group taking Crestor, though this statistic is not explained. But it is worth pointing out that the death rate for the study group as a whole (2.5%) was better than the death rate for this age group reported by census data and identical to the death rate for the age group being studied according to CDC statistics.  For stroke, there were 31 fewer strokes in the group taking Crestor and 3 fewer deaths. So Crestor looks a bit more helpful here.

But here’s the other bad news buried in The New England Journal of Medicine study: Both A1c and the incidence of diagnosed diabetes rose in the group taking Crestor.

There were 54 more cases of diabetes diagnosed in the Crestor group than in the placebo group. This is brushed off as barely significant by the authors, though, in fact, it is greater than the difference in heart attack, stroke, etc.

So what does this study tell us about Crestor?

1. Crestor makes a small difference in the cardiovascular health of people with high CRP.

2. This study confirms the suspicion that cholesterol levels are a red herring and that the impact of statins, where they have an impact, is on lowering inflammation in the cardiovascular system.

3. Crestor is more effective against microvascular problems than heart attack death, which makes sense if the main thing they do is decrease inflammation in small arteries most likely to lead to stroke.

4. Crestor lowers the number of heart attacks, but not the number of heart attack deaths.

5. Crestor appears to raise the incidence of diabetes in those taking it. The mechanism of this is not known.

6. The study did not find an increase in muscle or liver problems, but it carfully screened out those who most likely to develop these problems. Crestor has been linked to severe muscle and liver damage. 

7. The study did not investigate or report the incidence of cognitive decline in this group. Statins have been linked to cognitive decline (i.e. memory loss and other signs of dementia).

8. This study did not look at the impact of a much cheaper generic statin on the same endpoints. It was run and reported by people with strong financial links to AstraZeneca, the company that makes the expensive, patented Crestor. It is very possible that the benefits found with Crestor may also be achieved by taking the inexpensive generic statin, Simvastatin (Zocor).

9. This study was run by people with very strong financial links to the manufacturers of Crestor and who have additional financial motives to promote CRP testing. The way that they obscured the heart attack death statistic should make you careful about trusting their conclusions. See the list of conflicts of interest reproduced below.

NOW HERE IS WHY YOU SHOULD BE VERY CAREFUL TRUSTING THIS PUBLISHED NEW ENGLAND JOURNAL OF MEDICINE STUDY

Below is the disclosure paragraph listing the many cited conflicts of interest published with this study. The names listed first are those of the study’s authors.  The names of the pharmaceutical companies financially supporting these doctors and researchers through grants, consulting fees, lecture fees, etc. are listed after each of their names.  It reads like a “Who’s Who” of Giant Pharma:

Dr. Ridker reports receiving grant support from AstraZeneca, Novartis, Merck, Abbott, Roche, and Sanofi-Aventis; consulting fees or lecture fees or both from AstraZeneca, Novartis, Merck, Merck–Schering-Plough, Sanofi-Aventis, Isis, Dade Behring, and Vascular Biogenics; and is listed as a coinventor on patents held by Brigham and Women’s Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease, including the use of high-sensitivity C-reactive protein in the evaluation of patients’ risk of cardiovascular disease. These patents have been licensed to Dade Behring and AstraZeneca. Dr. Fonseca reports receiving research grants, lecture fees, and consulting fees from AstraZeneca, Pfizer, Schering-Plough, Sanofi-Aventis, and Merck; and Dr. Genest, lecture fees from AstraZeneca, Schering-Plough, Merck–Schering-Plough, Pfizer, Novartis, and Sanofi-Aventis and consulting fees from AstraZeneca, Merck, Merck Frosst, Schering-Plough, Pfizer, Novartis, Resverlogix, and Sanofi-Aventis. Dr. Gotto reports receiving consulting fees from Dupont, Novartis, Aegerion, Arisaph, Kowa, Merck, Merck–Schering-Plough, Pfizer, Genentech, Martek, and Reliant; serving as an expert witness; and receiving publication royalties. Dr. Kastelein reports receiving grant support from AstraZeneca, Pfizer, Roche, Novartis, Merck, Merck–Schering-Plough, Isis, Genzyme, and Sanofi-Aventis; lecture fees from AstraZeneca, GlaxoSmithKline, Pfizer, Novartis, Merck–Schering-Plough, Roche, Isis, and Boehringer Ingelheim; and consulting fees from AstraZeneca, Abbott, Pfizer, Isis, Genzyme, Roche, Novartis, Merck, Merck–Schering-Plough, and Sanofi-Aventis. Dr. Koenig reports receiving grant support from AstraZeneca, Roche, Anthera, Dade Behring and GlaxoSmithKline; lecture fees from AstraZeneca, Pfizer, Novartis, GlaxoSmithKline, DiaDexus, Roche, and Boehringer Ingelheim; and consulting fees from GlaxoSmithKline, Medlogix, Anthera, and Roche. Dr. Libby reports receiving lecture fees from Pfizer and lecture or consulting fees from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Pfizer, Sanofi-Aventis, VIA Pharmaceuticals, Interleukin Genetics, Kowa Research Institute, Novartis, and Merck–Schering-Plough. Dr. Lorenzatti reports receiving grant support, lecture fees, and consulting fees from AstraZeneca, Takeda, and Novartis; Dr. Nordestgaard, lecture fees from AstraZeneca, Sanofi-Aventis, Pfizer, Boehringer Ingelheim, and Merck and consulting fees from AstraZeneca and BG Medicine; Dr. Shepherd, lecture fees from AstraZeneca, Pfizer, and Merck and consulting fees from AstraZeneca, Merck, Roche, GlaxoSmithKline, Pfizer, Nicox, and Oxford Biosciences; and Dr. Glynn, grant support from AstraZeneca and Bristol-Myers Squibb. No other potential conflict of interest relevant to this article was reported.

Speak to a Crestor Lawyer about a Crestor Diabetes or Heart Lawsuit

If you or a loved one took the cholesterol drug Crestor (Rosuvastatin) and developed diabetes, heart failure, or a stroke please contact a Crestor Diabetes Lawsuit Attorney at our law firm immediately. It may be too late to recover from some the devastating effects of Crestor, but an experienced pharmaceutical products liability lawyer at the Willis Law Firm can assist you in legal action against AstraZeneca, the maker of this dangerous drug. You are not alone. Join other Crestor victims and their families in speaking up and fighting for your legal rights.

Please fill out our free online legal evaluation form and we will contact you within 24 hours, or call our offices at 1-800-883-9858 for immediate help. Please keep in mind that certain states have statutes of limitation that limit the amount of time you have to file a lawsuit or seek legal action. Contact our law firm immediately so that we may explain the rights and options available to you and your family.

AstraZeneca, the global top-ten pharmaceutical giant and manufacturer – marketer of the popular cholesterol drug Crestor (Rosuvastatin), is being confronted with the possibility of very serious and potentially life threatening sides effects associated its billion-dollar cholesterol drug.  Crestor (Rosuvastatin) is currently a very popular cholesterol lowering “statin” drug (category of all cholesterol lowering drugs).  Through independent research studies, Crestor, because of its unique formulation is being shown to have significantly higher potential risks for certain serious side effects.  According to documentation, the US Food and Drug Administration (FDA) appears to have not been aware of these risks when it approved Crestor for sale in the US in 2003.

One of the major side effects of Crestor (Rosuvastatin) is a potentially life threatening disorder known as Rhabdomyolysis.  Rhabdomyolysis is a muscle disease that depletes muscle-mass and strength in the human body.  Sometimes this muscle depletion occurs only in specific and limited areas of the body, while in some instances, the muscle-mass loss occurs over the entire body.  Regardless of which manifestation of Rhabdomyolysis occurs, the heart is clearly at risk.  In simple terms, Rhabdomyolysis can cause weakness and damage in the most important muscle in the body, the heart.

In a research study conducted by the independent watchdog group, Public Citizen, prescription data for Crestor was compared to that of other statin drugs. This research study showed that Crestor caused rhabdomyolysis almost 22 times more than its lowest dose competitor and 3 times more than its highest dose competitor. These are highly significant results.

The reason for the study’s outcome is that the higher the dose of the active ingredient, Rosuvastatin, the higher the risk of rhabdomyolysis. AstraZeneca, the Swiss drug giant, promotes Crestor as being the most powerful statin on the market.  This may be true, but at what cost to a patient’s health? Especially since Crestor’s advertised “strength” comes from a significantly higher dosage of Rosuvastatin, its active ingredient. Recent studies have shown that only 10 mg of Crestor (Rosuvastatin) has a significantly positive effect, but these positive benefits plateau and the negative side effects of rhabdomyolysis, heart failure, heart attack, stroke liver failure, kidney failure, and potentially diabetes increase significantly at the higher prescribed and advertised dosages.

At the higher prescribed dosages, Crestor may indeed have slightly better results, but the risks for heart damage, stroke, kidney damage, liver damage and even diabetes begin to far outweigh any possible extra benefits gained.

Crestor: Heart Attacks, Heart Failure and Strokes?

As with all statins a cholesterol patient will notice weakness and fatigue. If this turns into rhabdomyolysis, then the benefits of lower risk of heart attack through lower cholesterol and potentially unclogged arteries is soon undone. The potential problems of higher cholesterol are then replaced with a very real and long lasting disease that may be worse than the original cholesterol problem.  Rhabdomyolysis has the potential to cause a series of serious problems including heart attack, stroke, kidney failure, liver failure, and possibly even diabetes.

John Kjekshus of the University of Oslo and his colleagues conducted a study of 5000 cholesterol sufferers which showed that the benefits of Crestor were not as significant as advertised, when compared to a placebo (non-working dummy medication) in the study, but the weakening of the heart from rhabdomyolysis became a very major concern, especially in patients who were already at risk for possible heart failure.

“Our findings suggest the major cause of death in these patients was likely not to be related to atherosclerotic events, where benefit with statins in non-heart failure patients has been demonstrated, but instead may have been caused by the deterioration of failing heart muscle damaged beyond repair,” John Kjekshus of the University of Oslo said.

There is a difference between a heart attack and heart failure. Heart failure is a hard-to-treat condition in which the weakened heart cannot pump enough blood to meet the body’s need for oxygen, causing shortness of breath or other complications. Heart failure is a leading cause of hospitalization among the elderly.

But at a certain point the depletion of the heart muscle from rhabdomyolysis leads not only to heart attacks, but also to strokes. Strokes are due to the lack of blood pressure flowing through the brain from the heart potentially weakened by rhabdomyolysis. Strokes can lead to paralysis, loss of speech, severely degraded cognitive ability or death.

The Swiss drug giant AstraZeneca produced and heavily marketed Crestor to profit from the increased awareness of high-cholesterol and its potential serious affects on the health of some as they age. Crestor, having a significantly higher dose of rosuvastatin as compared to other statins, makes it unique.  This significantly higher dosage may actually be the wrong approach to the root cause of the problem of high cholesterol. In actuality, this formulation may make the side effects much, much worse, with few if any additional benefits to warrant the increased risk.

The increased dosage of Crestor has been found in a study conducted by Public Citizen to cause Crestor patients to also have renal (kidney) failure 75 times more than other statins. That is a much higher risk of kidney failure with Crestor than with other statins. This is an especially major risk and complication for cholesterol patients who may have already had kidney problems or may be suffering from liver damage at the time they are prescribed Crestor.

These study results prompted a request to the FDA in 2004 that they take Crestor off of the market. The FDA responded to that request with the results of AstraZeneca-sponsored research projects, and a firm refusal. The FDA has currently yet to revise or strengthen the side effects and warnings on the drug package label or order any other independent studies of their own to address these claims or to resolve the issue through research and objective science.

AstraZeneca’s sales of Crestor have been rising steadily with sales of more than $2.5 billion per year in 56 markets around the world. In other words, millions upon millions of cholesterol patients worldwide, some already with diminished heart, kidney and liver functionality, are being put at risk of the serious and possibly life threatening Crestor side effects.  According the referenced studies, Crestor’s side effects include heart failure, heart attack, stroke, kidney failure, liver failure, and diabetes, among other health risks.

Speak to a Crestor Lawyer about a Crestor Heart Failure Lawsuit

If you or a loved one took the cholesterol drug Crestor (Rosuvastatin) and experienced heart failure, stroke, kidney failure or liver failure please contact a Crestor Lawsuit Attorney at our law firm immediately. It may be too late to recover from some the devastating effects of Crestor, but an experienced pharmaceutical products liability lawyer at the Willis Law Firm can assist you in legal action against AstraZeneca, the maker of this dangerous drug. You are not alone. Join other Crestor victims and their families in speaking up and fighting for your legal rights.

Please fill out our free online legal evaluation form and we will contact you within 24 hours, or call our offices at 1-800-883-9858 for immediate help. Please keep in mind that certain states have statutes of limitation that limit the amount of time you have to file a lawsuit or seek legal action. Contact our law firm immediately so that we may explain the rights and options available to you and your family.

Use of Selective Serotonin-Reuptake Inhibitors in Pregnancy and the Risk of Birth Defects

Sura Alwan, M.Sc., Jennita Reefhuis, Ph.D., Sonja A. Rasmussen, M.D., M.S., Richard S. Olney, M.D., M.P.H., and Jan M. Friedman, M.D., Ph.D. for the National Birth Defects Prevention Study

N Engl J Med 2007; 356:2684-2692 June 28, 2007

Background

Information regarding the safety of selective serotonin-reuptake inhibitors (SSRIs) in human pregnancy is sparse. Concern has been raised about the risk of congenital heart defects associated with the use of SSRIs during pregnancy.

Methods

We obtained data on 9622 case infants with major birth defects and 4092 control infants born from 1997 through 2002 from the National Birth Defects Prevention Study. Case infants were ascertained through birth-defects surveillance systems in eight U.S. states; controls were selected randomly from the same geographic areas. Mothers completed a standardized telephone interview regarding exposure to potential risk factors, including medications, before and during pregnancy. Exposure to SSRIs was defined as treatment with any SSRI from 1 month before to 3 months after conception. Birth defects were assigned to 26 categories and subcategories.

Results

There were no significant associations between maternal use of SSRIs overall during early pregnancy and congenital heart defects or most other categories or subcategories of birth defects. Maternal SSRI use was associated with anencephaly (214 infants, 9 exposed; adjusted odds ratio, 2.4; 95% confidence interval [CI], 1.1 to 5.1), craniosynostosis (432 infants, 24 exposed; adjusted odds ratio, 2.5; 95% CI, 1.5 to 4.0), and omphalocele (181 infants, 11 exposed; adjusted odds ratio, 2.8; 95% CI, 1.3 to 5.7).

Conclusions

Maternal use of SSRIs during early pregnancy was not associated with significantly increased risks of congenital heart defects or of most other categories of birth defects. Associations were observed between SSRI use and three types of birth defects, but the absolute risks were small, and these observations require confirmation by other studies.

The lifetime risk of major depression among women is 10 to 25%, with a peak prevalence during childbearing years. Selective serotonin-reuptake inhibitors (SSRIs) are the most frequently used class of antidepressant medications in general and during pregnancy. Data on the safety of SSRIs in human pregnancy are limited, but recent investigations suggest that maternal use of SSRIs during pregnancy may be associated with birth defects in general or with congenital heart defects in particular.

We used data from the National Birth Defects Prevention Study (NBDPS) to evaluate the relationship between maternal SSRI use in early pregnancy and the occurrence of selected birth defects.

Methods

Study Subjects and Data Collection

The NBDPS is an ongoing, multisite, case–control study of environmental and genetic risk factors for more than 30 selected categories of major birth defects. Case infants had received a diagnosis of at least one selected birth defect and were ascertained by population-based birth-defects surveillance systems at eight study sites (Arkansas, California, Georgia, Iowa, Massachusetts, New Jersey, New York, and Texas). We used data from infants who were born on or after October 1, 1997, and who had an estimated date of delivery on or before December 31, 2002. Case infants were born alive (all participating sites) or died at 20 weeks or more of gestation (Arkansas, California, Georgia, Iowa, Massachusetts, and Texas). Pregnancies with reliably ascertained defects that were electively terminated were also included in Arkansas, California, Georgia, Iowa, and Texas. Infants with recognized or strongly suspected chromosomal abnormalities or single-gene conditions were excluded from the study.

The controls were live-born infants with no major birth defects who were randomly selected from hospital or state birth-certificate records from the same geographic areas. Only one case or control infant was included from each multifetal pregnancy.

Birth defects for which at least 200 case mothers were interviewed were selected for the analysis. This number was determined as that needed to obtain 80% power with an odds ratio of 2.5, given a 2.1% exposure rate to SSRIs among control mothers. Information on the infants in each defect category was reviewed by clinical geneticists who were unaware of the infants’ exposure status, who confirmed case eligibility and classified the cases as isolated (no additional major unrelated defect) or multiple (more than one major unrelated birth defect). To reduce pathogenetic heterogeneity, cases with complex sequences (e.g., omphalocele–exstrophy–imperforate anus–spinal defects phenotype) were excluded, and isolated defects were analyzed separately. A total of 709 infants who had more than one eligible birth defect were included in multiple analyses. Each case of a cardiac birth defect was reviewed by a team of experts in pediatric cardiology and the epidemiology of heart defects and was assigned to a single cardiac diagnostic category.

Demographic information and information on exposure to SSRIs and other potential risk factors during pregnancy were collected by standardized telephone interviews with mothers of case and control infants conducted in English or Spanish from 6 weeks to 2 years after the estimated date of delivery. Infants for whom complete maternal interviews were unavailable were excluded. The participation rates among case and control mothers were 71.1% and 68.6%, respectively. The mothers were asked whether they had taken any of three specific SSRIs, identified by brand name — Prozac (fluoxetine), Zoloft (sertraline), and Paxil (paroxetine) — during and before pregnancy, and when each medication was taken. They were also asked about their use of other medications during this period, which enabled us to analyze associations with other SSRIs. Exposure was defined as reported use of any SSRI from 1 month before to 3 months after conception (the date of conception was calculated as 266 days before the estimated date of delivery). Women were considered unexposed if they did not take an SSRI at any time during pregnancy or during the 3 months before conception. Women who took non-SSRI antidepressants were included in the unexposed group.

Statistical Analysis

Our hypothesis for this exploratory study was that SSRI exposure early in pregnancy is associated with one or more of the selected categories of birth defects. Crude analyses were performed by Pearson’s chi-square test, and odds ratios and (if the expected number in a cell was less than five) Fisher’s exact confidence limits were calculated with SPSS software, version 10.0, and with SABER, with the use of the same control group for every comparison.

The following potential confounders were evaluated: maternal race or ethnic group (non-Hispanic white vs. other), maternal age (under 35 years of age vs. 35 or older), maternal education (12 years or less vs. more than 12 years), prepregnancy obesity (body-mass index [the weight in kilograms divided by the square of the height in meters] <30 vs. ≥30), maternal smoking or alcohol use from 1 month before to 3 months after conception, maternal folic acid use from 1 month before to 1 month after conception, annual family income (less than $20,000 vs. $20,000 or more), singleton versus multiple pregnancy, parity (no previous live births vs. one or more previous live births), and presence or absence of prepregnancy hypertension. Potential confounders were first evaluated for associations with SSRI exposure and with each of the specific defects, and they were excluded from the logistic regression if their removal resulted in a change in risk estimate of less than 10%. All confounders retained in the model for any of the defects were included in the final models for all defects. Infants of mothers with prepregnancy type 1 or 2 diabetes were excluded from adjusted analyses because of the strong association of diabetes with birth defects.

For the defects with positive associations, we performed post hoc analyses of SSRIs stratified according to factors that were associated both with maternal SSRI use and with the outcomes. These factors were maternal race or ethnic group, age, education, presence or absence of obesity, presence or absence of smoking, presence or absence of hypertension, and singleton versus multiple pregnancy. After identification of effect modification by obesity for craniosynostosis, as indicated by the Breslow–Day test, we further evaluated the effect of obesity on all defects by performing analyses with a four-level variable (obesity alone, SSRI exposure alone, both SSRI exposure and obesity, neither SSRI exposure nor obesity) by asymptotic and Fisher’s exact logistic regression with the use of LogXact software, version 4.0.

We also performed crude and adjusted analyses for isolated defects only and assessed the associations between four specific SSRIs (fluoxetine, sertraline, paroxetine, and citalopram [Celexa]) and 4 combined birth-defect categories and between three specific SSRIs (fluoxetine, sertraline, and paroxetine) and 16 categories of birth defects when there were at least three exposed infants. Additional analyses were performed assessing the association between the use of any SSRI during two other time intervals of pregnancy and 16 categories of birth defects. No adjustment was made for the multiple comparisons performed.

Results

Eighteen categories of birth defects and eight subcategories of cardiac birth defects met the criterion of being represented by at least 200 interviews with case mothers. Interviews were incomplete for 163 case or control mothers, and 5 mothers reported depression but did not report use of antidepressants. These subjects were excluded from the analysis, leaving 9622 case and 4092 control infants.

Of the 13,714 case and control mothers included, 408 (3.0%) reported using an SSRI at some point before or during pregnancy. The reported frequency of SSRI use in the period from 1 month before to 3 months after conception was 2.3%; 230 mothers of case infants (2.4%) and 86 mothers of control infants (2.1%) reported using an SSRI. The SSRI most commonly used by control mothers was sertraline (0.8%), followed by fluoxetine (0.7%), paroxetine (0.5%), and citalopram (0.2%).

Control mothers were significantly more likely than case mothers to be younger than 35 years of age, to have more than 12 years of education, and to have a higher family income. Case mothers were more likely than control mothers to smoke, have diabetes, have hypertension, and be obese.

For two defects, anotia or microtia and intestinal atresia, there was only one exposed case, and therefore these defects were excluded from further individual analyses. Of the 16 remaining categories and 8 subcategories, 3 showed significant associations with SSRI use: anencephaly (214 infants, 9 exposed), craniosynostosis (432 infants, 24 exposed), and omphalocele (181 infants, 11 exposed)

Confounders that met our criteria were maternal race or ethnic group, maternal obesity, maternal smoking, and family income, and these were included in the adjusted analyses.

After post hoc analyses assessing potential effect modification by seven variables showed significant effect modification by obesity for the association between SSRI use and craniosynostosis (P=0.05, by the Breslow–Day test), we performed additional exploratory analyses of effect modification by obesity for all categories of defects using a four-level variable available with the full text of this article at www.nejm.org). Among women who did not use SSRIs, obese women were more likely than nonobese women to have infants with conotruncal heart defects (adjusted odds ratio, 1.3; 95% confidence interval [CI], 1.0 to 1.6) and septal heart defects (adjusted odds ratio, 1.3; 95% CI, 1.1 to 1.5). The associations were stronger among women reporting SSRI use: for conotruncal heart defects, the adjusted odds ratio was 3.5 and the 95% CI was 1.4 to 8.7; for septal heart defects, the adjusted odds ratio was 2.8 and the 95% CI was 1.3 to 6.4. Among nonobese women, SSRI use was associated with craniosynostosis (adjusted odds ratio, 2.0; 95% CI, 1.1 to 3.7), but the risk was greater among obese women who reported SSRI use (adjusted odds ratio, 5.9; 95% CI, 2.4 to 14.3).

Restricting the analyses to infants with isolated defects resulted in wider confidence intervals and a loss of statistical significance, although there were only slight reductions in the odds ratios. Restricting the exposure period to the first 2 months of pregnancy did not change the estimates appreciably (data not shown). Since the critical period for the development of craniosynostosis may extend beyond the first trimester, we examined SSRI use during the second and third trimesters and found a lower odds ratio (17 exposed; adjusted odds ratio, 1.9; 95% CI, 1.0 to 3.5). Sixteen of these women were also exposed to an SSRI during the first trimester.

In additional post hoc analyses, we assessed the associations between the use of four specific SSRIs and the risks of all 18 evaluated birth defects combined and of specific groups of birth defects. None of the individual SSRIs were associated with significantly increased risks of all 18 birth defects combined, the 4 cardiac birth defects combined, or the 14 noncardiac birth defects combined. The use of paroxetine or citalopram significantly increased the risk of the pooled group of anencephaly, craniosynostosis, and omphalocele.

We also assessed the association between the three most commonly used SSRIs (fluoxetine, sertraline, and paroxetine) and 16 specific categories of birth defects, but these analyses were limited by the small numbers of exposed cases for each category. We found one significant association each for fluoxetine and sertraline: fluoxetine use was associated with craniosynostosis (10 exposed infants; adjusted odds ratio, 2.8; 95% CI, 1.3 to 6.1) and sertraline use with anencephaly (4 exposed infants; adjusted odds ratio, 3.2; 95% CI, 1.1 to 9.3). We found four significant associations for paroxetine: with anencephaly (five exposed infants; adjusted odds ratio, 5.1; 95% CI, 1.7 to 15.3), right ventricular outflow tract obstruction defects (seven exposed infants; adjusted odds ratio, 2.5; 95% CI, 1.0 to 6.0), omphalocele (six exposed infants; adjusted odds ratio, 8.1; 95% CI, 3.1 to 20.8), and gastroschisis (five exposed infants; adjusted odds ratio, 2.9; 95% CI, 1.0 to 8.4). None of the mothers of case infants with defects found to be associated with SSRI use were concomitantly exposed to medications with a known teratogenic effect.

Discussion

Using data from a population-based case–control study, we found no significant associations between the use of SSRIs in early pregnancy and the risks of the majority of birth defects assessed in this study, including congenital heart defects. However, we observed associations between SSRI use and the occurrence of anencephaly, craniosynostosis, and omphalocele, defects that had not been previously associated with maternal SSRI use in pregnancy.

Studies in animals have demonstrated delayed ossification in offspring after maternal treatment with sertraline. A specific role of serotonin in cardiac and craniofacial morphogenesis in the rodent embryo has also been established. Several recent reports have suggested possible associations between maternal use of paroxetine during pregnancy and birth defects in humans. A report from the Swedish Medical Birth Register showed an increased risk of heart defects overall, and of ventricular and atrial septal defects specifically, among infants whose mothers took paroxetine (but not other SSRIs). That report did not find the associations we observed between SSRI use and craniosynostosis or abdominal wall defects (omphalocele and gastroschisis were not examined separately).

An unpublished analysis of administrative records from a managed care organization showed an increased risk of major birth defects overall, and of heart defects specifically, among infants whose mothers received prescriptions for paroxetine as compared with those whose mothers received prescriptions for other antidepressants during pregnancy. Similar results were shown in another unpublished cohort study among women treated with paroxetine during the first trimester as compared with women who did not take SSRIs. A cohort study based on administrative data from Quebec, Canada, showed that the risks of major birth defects and of heart defects were greater among infants whose mothers took high doses of paroxetine during early pregnancy than among those whose mothers took non-SSRI antidepressants, but this association was not seen among infants whose mothers took lower doses of paroxetine.

In a Finnish cohort study, the overall risk of major malformations was not significantly increased among infants born to women treated with fluoxetine during the first trimester, but an increase in the risk of heart defects by a factor of three was noted. A Danish cohort study showed an increased risk of congenital malformations in general among women given prescriptions for any SSRI. Other epidemiologic studies have not shown a significant association between major birth defects and maternal SSRI use during pregnancy. However, all previous studies have had limitations, such as insufficient power, issues with ascertainment or classification of birth defects, inability to address potential confounding, or poor information on exposure.

Some, but not all, of our findings are consistent with those of another large case–control study in this issue of the Journal. Like our report, that study showed no significant associations between SSRI use overall and congenital heart defects. It did show significant associations between paroxetine use and right ventricular outflow tract obstruction defects (six infants; adjusted odds ratio, 3.3; 95% CI, 1.3 to 8.8) and neural-tube defects (four infants; adjusted odds ratio, 3.3; 95% CI, 1.1 to 10.4; anencephaly and spina bifida were not examined separately). However, that report found no significant association between craniosynostosis and SSRI use, and for omphalocele it found a significant association only with sertraline.

Our study is population-based and includes a large birth sample, allowing the evaluation of the relationship between SSRI use and specific types of birth defects. The study also uses careful case definitions and review and excludes infants with chromosomal abnormalities and single-gene disorders. Although the large size of our study overall allowed for consideration of several potential confounders and effect modifiers, the small number of exposed infants for each individual defect remains a limitation.

Because of the large number of comparisons evaluated in our analysis, it is likely that some of the observed associations reflect chance variation. We performed a total of 265 tests, with 54 positive results at the 0.05 significance level; we would have expected 14 positive results to occur by chance. Not all positive tests are reported, and it is not possible to identify which, if any, of the observed associations are due to chance alone. Analyses of other data sets are warranted to replicate our findings.

The effect modification by prepregnancy obesity that we observed post hoc for the association between SSRI use and the occurrence of some birth defects has not, to our knowledge, been reported previously, and confirmation is needed. However, maternal obesity itself has been associated with increased risks of neural-tube defects, congenital heart defects, and other defects. The effect modification we observed may reflect differences in the pharmacokinetics of these lipophilic drugs in women with various percentages of body fat.

An important limitation of this study is our inability to separate the effect of maternal SSRI use from that of the underlying depression. Only 39 case or control mothers reported having had depression when asked a general question about illnesses during pregnancy. All but five of these women reported taking an antidepressant medication before or during pregnancy. Data on dosage were unavailable, so that analysis of dose–response relationships could not be performed. When they were questioned about the use of medications, the mothers were prompted by brand names for the three most commonly used SSRIs, leading to potential underreporting of other SSRIs. Exposures were determined by maternal report, which introduces a potential for recall bias. Selection bias may have occurred, because participation was less than 100%; however, it is unlikely that participation varied according to SSRI exposure status, and therefore any selection bias was probably in favor of the null hypothesis.

Our study did not show an increased risk of most birth defects, and SSRI exposure was present in only a small number of cases of certain defects. The absolute risks associated with SSRIs appear small in comparison with the baseline risks of birth defects that exist in every pregnancy. Maternal stress and depression during pregnancy have been associated with adverse reproductive outcomes, and discontinuation of antidepressant treatment in pregnant women with serious depressive illness may have adverse effects on the mother and her baby. Thorough assessment of the potential risks and benefits of SSRI use is necessary to allow women of reproductive age to make informed decisions about such therapy.

The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.

Dr. Friedman reports receiving honoraria for consulting from I3 Research. No other potential conflict of interest relevant to this article was reported.

We thank all the families participating in the National Birth Defects Prevention Study (NBDPS) and all NBDPS investigators. We also thank Drs. Margaret A. Honein and Owen Devine for their valuable input. Coding of drug information in the NBDPS used the Slone Drug Dictionary, under license from the Slone Epidemiology Center at Boston University, Boston.

Source Information

From the Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada (S.A., J.M.F.); and the National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta (J.R., S.A.R., R.S.O.).

Zoloft Class Action Heart Defect Lawsuit vs. Individual Zoloft Lawsuit

There are distinct differences between a Zoloft (sertraline) class action heart defect lawsuit and a more typical individual Zoloft heart defect lawsuit. A Zoloft class action heart defect lawsuit would be a form of Zoloft lawsuit in which a large group of people (Zoloft plaintiffs) collectively bring a Zoloft heart defect lawsuit to court in the form of a “class action” against the manufacturers of Zoloft (defendant). In a Zoloft class action heart defect lawsuit involving personal injury, resulting from defective products such as antidepressant SSRI drugs like Zoloft (sertraline), Paxil (paroxetine), Prozac (fluoxetine) and Celexa (citalopram), all Zoloft lawsuit plaintiffs would typically be grouped together into a single Zoloft class action lawsuit, regardless of the degree or severity of their Zoloft birth defect injuries. In this type of Zoloft class action lawsuit, Zoloft plaintiffs with injuries ranging from minor heart murmurs not requiring surgery, all the way to the most severe congenital Zoloft heart defects, requiring multiple surgeries or even a complete heart transplant, would be grouped into one single Zoloft class action lawsuit. All Zoloft plaintiffs in the class would equally share any award or settlement resulting from the Zoloft class action lawsuit.

In Zoloft lawsuits involving catastrophic injury or death, an individual Zoloft lawsuit, in most cases, is more appropriate and in the Zoloft plaintiff’s best interest. SSRI antidepressants like Zoloft, Prozac, Celexa and Paxil (paroxetine), have been linked to severe congenital heart defects, including: atrial septal defects (ASD – hole in the heart), ventricular septal defects (VSD – hole in the heart), tetrology of fallot (ToF), hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA or TOGA), patent ductus arteriosus (PDA), total anomalous pulmonary venous return (TAPVR), double outlet right ventricle (DORV), and coarctation of the aorta (CoA). Zoloft cases such as these are better suited to an individual Zoloft lawsuit because of the severity and degree of injury to the Zoloft plaintiff. In an individual Zoloft Lawsuit, each Zoloft plaintiff’s case is filed, presented and considered individually, based on its own strength and degree of injury.

In many cases involving SSRI antidepressants like Zoloft, Prozac, Celexa, Paxil and the serious congenital heart defects related to these SSRI antidepressants,  heart defect surgery is required. Heart surgery will typically be required when a child is an infant or toddler and then again, potentially multiple times, as the child grows to maturity. In many cases, with surgery and medical care, children born with a  heart defect may be able to lead mostly normal and productive lives. An individual Zoloft heart defect lawsuit allows each Zoloft victim, their heart defect injuries and their future needs to be considered on an individual basis when determining damages, awards and settlement amounts, and not as part of a Zoloft class action lawsuit.

Speak to a Zoloft Heart Defect Lawsuit Lawyer

If you took Zoloft or generic sertraline during pregnancy and your child was born with a heart birth defect or a lung birth defect, we encourage you to contact a Zoloft heart defect litigation attorney at our law firm immediately. It may be too late to recover from the devastating effects of Zoloft heart defects, but an experienced products liability Zoloft attorney at the Willis Law Firm can assist you in legal action against the makers of Zoloft. You are not alone. Join other Zoloft heart defect, Zoloft lung defect, and other Zoloft birth defect victims and their families in speaking up and fighting for your legal rights.

Zoloft Birth Defect Lawsuit

Please fill out our free online legal evaluation form and we will contact you within 24 hours. Please keep in mind that certain states have statutes of limitation that limit the amount of time you have to file a lawsuit or seek legal action. Contact a Zoloft heart defect lawyer at our law firm immediately so we may explain the rights and options available to you and your family.

Here is an important new warning about the heart drug Multaq (generic name: dronedarone), which is linked to severe liver injury. See also: Multaq Liver Failure Lawsuits.

Subject: Updated Safety Information for Multaq® (dronedarone) related to liver injury

Sanofi-aventis Canada Inc., in collaboration with Health Canada would like to inform patients of new important safety information related to liver injury, reported in patients treated with Multaq. Multaq helps control abnormal heart rate and rhythm called atrial fibrillation and can lower the risk of having to go into the hospital for heart problems.

• Patients should discuss with their healthcare professionals this new safety information regarding Multaq treatment.
• Patients treated with Multaq should immediately report to their doctors symptoms possibly suggesting liver injury (such as: Loss of appetite, nausea, vomiting, unusual tiredness, right upper stomach area pain or discomfort, yellowing of the skin or the whites of the eyes (jaundice), unusual darkening of the urine, or itching) and patients should consider obtaining periodic liver function tests.

Sanofi-aventis has been working with Health Canada, and the Multaq Product Monograph was revised to include this new safety information.

Please speak with your doctor or pharmacist if you have any related concerns or if you experience any other unexpected effects while taking Multaq.

Studies Link Seizure Medication Depakote to Birth Defects

“There is no question in my mind that Depakote causes birth defects,” stated Dr. Wyszynski

Houston, Texas – Babies born to women taking Depakote (valproate), the commonly prescribed anti-seizure medication, were 5 times more likely in one study, and 14 times more likely in another study, to suffer from serious birth defects and other congenital problems, including spina bifida and other neural tube defects.  Furthermore, researchers also stated that women should avoid taking Depakote, if possible, during childbearing years.

In a recent study by Page Pennell, MD, of Atlanta’s Emory University School of Medicine that was presented at the American Academy of Neurology, it was shown that birth defect problems were far more common when women took Depakote during pregnancy when compared to women who took other anti-epileptic drugs.

Birth defects, developmental delays and death of the fetus occurred in 28% of children whose mothers took Depakote when compared to just 2% of children whose mothers took other anti-seizure drugs, in the case of this study, the newer drug Lamictal.

Similar complications were also noted with the use of some other anti-seizure medications during pregnancy, but not nearly to the same degree as with the use of Depakote. Among other anti-seizure drugs, only 10% of children whose mothers took Tegretol and 7% of children born to mothers who took Dilantin experienced such problems. Again, 28% of children whose mothers took Depakote suffered from spina bifida, neural tube defects or other birth defect complications.

The oldest children in this quoted study are now 8 ½, and researchers from Atlanta’s Emory University School of Medicine, say that these children suffering from Depakote induced birth defects still need to be monitored for at least a few more years to see how the serious defects and developmental differences persist or further develop.

Strong Evidence Mounting Against Depakote

According to the study, many women taking anti-seizure medications for epilepsy may need to consider staying on the drugs during pregnancy, since uncontrolled seizures during pregnancy may in some cases cause miscarriage.  Also, the serious risk of not being able to regain control of a patient’s seizures after stopping an anti-seizure medication is always present.  In many instances, this risk exists in spite of being able to restart the exact same anti-epileptic drug that was effective, at a later time.

The moral question then becomes:

“If a woman had all of the facts regarding the potentially catastrophic birth defect side effects of Depakote, like spina bifida, and fully understood the risks to her unborn child associated with the use of Depakote while pregnant, would she have chosen to use Depakote?”

The answer to that question may not be known, but most would agree that every woman is entitled to have a full knowledge of the birth defect risks associated with Depakote in making educated decisions before getting pregnant.  It would be safe to assume that some family planning decisions would be greatly affected by the knowledge that Depakote has such serious risks of potentially catastrophic birth defects like spina bifida.

Knowing what we know now about the strong link between Depakote use by women while pregnant and the occurrence of neural tube birth defects such as spina bifida, pharmaceutical companies and the medical community need to ensure that pregnant women and their doctors have full access to the data related to Depakote and spina bifida.

At this point in time, no woman who was prescribed Depakote while pregnant should have to ask the question: “What caused my baby’s spina bifida?” 

Conventional wisdom has always been that taking seizure medication doubles a pregnant woman’s risk of having a child with birth defects. But the study showed that it is becoming very clear that certain anti-seizure drugs like Depakote carry a far greater risk of birth defects than even previously thought. When compared to the drug Lamictal, Depakote has a 10 times greater risk for serious birth defects.

“The evidence against the use of Depakote by women during pregnancy is mounting, but the message has not gotten out,” the study says. “This drug is being increasingly prescribed for other conditions like migraines, bipolar disorder, and mood disorders.”

Researchers in the study actually presented data from the five-year study a year early, because the findings were so striking.

A spokesman for Depakote manufacturer Abbott Laboratories stated that the fact that only 25 women in the study took the drug could easily have distorted the findings.

“Depakote has been around for more than 20 years, and more than 3 million people have been treated with it,” said the spokesman for Abbott Labs. “Untreated epilepsy has potentially serious or fatal consequences for both the mother and the child.”

More Negative Evidence on Depakote Regarding Birth Defects

Another study has also shown greatly increased rates of problems in children whose mothers took Depakote during pregnancy. This research will be presented in Vancouver this summer at a meeting of birth defect specialists.

In this latest study investigators followed 149 women with epilepsy who took Depakote, from early on in their pregnancies through the period following their deliveries.

In that study, it was found that among mothers who took Depakote, 11% had children with birth defects, the most common of which was spina bifida, a neural tube defect in which spinal cord development is incomplete or deformed. The same type of spina bifida and other neural tube defects were seen in only 3% of children of pregnant women taking all other anti-seizure drugs studied combined.  In this same study, less than 2% of children born to mothers without epilepsy had similar congenital birth defects. The results of this study point to a 500% greater risk for birth defects or other complications when pregnant women took Depakote during their pregnancies.

According to this latest study, all pregnant women who were taking Depakote also either took a prenatal multivitamin and/or folic acid supplements during the term of their pregnancies. It is generally recommended that women who are pregnant or might become pregnant take 400 micrograms of folic acid daily to prevent spina bifida. According to the researchers in this study, women taking Depakote may actually need to take more than 10 times that amount of folic acid to possibly try and counter the effects of Depakote, although this has not been definitively proven yet.

“There is no question in my mind that Depakote causes birth defects,” stated Dr. Wyszynski of the study. “Women who do not have to take it shouldn’t, but those who do may be able to decrease the risk of spina bifida birth defects in their children by taking higher doses of folic acid.”

Depakote – Possible Other Options

According to representatives at the American Epilepsy Foundation, the good news from the Pennell study is that it showed a much lower rate of spina bifida and other birth defect problems and complications seen with the use of some of the newer anti-seizure medications. As previously stated in this article, sixty women in the Pennell study took the newer drug Lamictal, with only 2% of their children having the same birth defect problems that occurred in a full 28% of children born to pregnant mothers taking Depakote during their pregnancies. The fact still remains that in Pennell study, there was shown to be a 1400% greater risk of suffering  birth defects and other complications associated with the taking of Depakote by women while pregnant than there was associated with taking a newer medication like Lamictal.  Restated, that represents 14x greater risk of birth defects with Depakote.

“We have been suspicious for some time that our full appreciation of the potential adverse effects of various anticonvulsive drugs on fetal development has not been completely understood. Studies like this one [the Pennell Study] are exactly what we need to get as close to the truth as we can” – Daniel Lowenstein, President of the American Epilepsy Foundation

Depakote Spina Bifida Class Action  Lawsuit vs. Individual Depakote Lawsuit

There are great differences between an individual Depakote (valproate) Spina Bifida lawsuit and a Depakote Spina Bifida class action lawsuit.

In most instances, a Depakote Spina Bifida lawsuit that involves severe birth injuries is better served by having a lawyer file an individual Depakote Spina Bifida lawsuit.  In an individual Depakote Spina Bifida lawsuit, the plaintiffs’ cases are filed by a lawyer and presented on their own merit, individually.

In class action Depakote Spina Bifida lawsuits, a group of victims typically are joined to form a “class”, which in this case a lawyer would bring to court as a class action lawsuit against Abbott Laboratories, the manufacturer of Depakote (valproate). All potential Depakote Spina Bifida plaintiffs would be grouped into a single Depakote Spina Bifida class action lawsuit, regardless of the severity of spina bifida or neural tube injuries. Depakote victims in a Depakote Spina Bifida class action lawsuit would then only share any resulting settlements or awards from the Depakote Spina Bifida class action lawsuit.

On the other hand, individual Depakote (valproate) Spina Bifida lawsuits filed by lawyers allow each Depakote Spina Bifida plaintiff to have their own individual case considered on an singular basis when damages, awards and settlement figures are considered.  In individual Depakote Spina Bifida lawsuits, awards or settelments are based on an individual victim’s current spina bifida injuries and all of their future and potential spina bifida needs, and not as part of a grouped class action lawsuit.

Speak to a Depakote Lawyer

If you took Depakote (valproate) or any other anti-seizure drug during pregnancy and your child was born with a Spina Bifida birth defect, please contact a Depakote Spina Bifida Litigation Attorney at our law firm immediately. While it may be too late to recover from all of the devastating effects of Depakote an experienced products liability pharmaceutical lawsuit lawyer at the Willis Law Firm can assist you in any legal action against Abbott Laboratories, the maker of Depakote. You are not alone. Join other Depakote Spina Bifida and other neural tube birth defect victims and their families in speaking up and fighting for your legal rights.

Depakote Spina Bifida Lawsuit

Please fill out our free online legal evaluation form and we will contact you within 24 hours. Please keep in mind that certain states have statutes of limitation that limit the amount of time you have to file a lawsuit or seek legal action. Contact our law firm immediately so that you can speak to a Depakote lawyer and so that we may explain the rights and options available to you and your family.

Here is an important new warning about the heart drug Multaq (generic name: dronedarone), which is linked to severe liver injury. See also: Multaq Liver Failure Lawsuits.

Subject: Updated Safety Information for Multaq® (dronedarone) in regards to hepatocellular liver injury

Dear Health Care Professional,

Sanofi-aventis Canada Inc. in collaboration with Health Canada, would like to inform you of important new safety information regarding Multaq (dronedarone).

During the 16 months following the initial launch of Multaq (July 20th, 2009), 155 post-marketing cases (87 serious cases) reporting hepatobiliary adverse events, including rare cases of hepatic failure, have been received. Some cases were suspected of drug-induced hepatic injury with a predominant hepatocellular pattern of injury, including two foreign post-marketing case reports of acute hepatic failure requiring transplantation. A definitive causal relationship between Multaq and these cases has not been established.

Exposure to Multaq through September 2010 was estimated at 79,503 patient-years.

Multaq is indicated for the treatment of patients with a history of, or current atrial fibrillation to reduce the risk of cardiovascular hospitalization due to atrial fibrillation.

• Healthcare professionals should discuss with their patients this new important safety information regarding Multaq treatment.
• Patients treated with Multaq should be advised to immediately report symptoms suggesting hepatic injury (such as anorexia, nausea, vomiting, fatigue, right upper abdominal quadrant pain, jaundice, dark urine, or itching).
• It has not been established that routine periodic monitoring of hepatic enzymes would enable early detection of severe liver injury. However, healthcare professionals should consider obtaining periodic hepatic serum enzymes, especially during the first 6 months of treatment.
• If hepatic injury is suspected, Multaq should be discontinued immediately and followed by necessary blood tests.
• The safety of restarting Multaq in patients who have sustained liver injury from any cause is unknown; accordingly, its use in such patients is not recommended.

The two cases of acute hepatic failure requiring transplantation occurred at 4.5 and 6 months after initiation of Multaq in patients with previously normal hepatic serum enzymes. Both patients were female and approximately 70 years of age.

In the first case, the patient had underlying intermittent atrial fibrillation, arterial hypertension and stable coronary artery disease. She was treated with Multaq for 4.5 months. Two weeks prior to hospitalization she reported increased exhaustion and tiredness. One week prior to admission she discontinued Multaq, and at the time of admission she was noted to have jaundice, coagulopathy, transaminitis and hyperbilirubinemia, which progressed to hepatic encephalopathy over the next nine days. A pre-transplant workup did not reveal another etiology of liver failure.

In the second case, the patient had a medical history of paroxysmal atrial fibrillation and Sjögren’s syndrome. Following 6 months of treatment with Multaq, she developed weakness, abdominal pain, coagulopathy, transaminitis and hyperbilirubinemia. She was transplanted 1 month later; no alternate etiology for liver failure was identified in the transplant work-up. In both cases, the explanted liver showed evidence of extensive hepatocellular necrosis.

Sanofi-aventis has been working with Health Canada, and the Multaq Product Monograph was revised to include this new safety information.

Topamax (Generic Name: topiramate) has been used alone or in combination with other drugs to treat some seizure types in patients having epilepsy. Topamax is used to control seizures in Lennox-Gastaut syndrome, which causes seizures and developmental delays. Topamax has been used in treating people who still have seizures even after taking several other types of anti-seizure anti-eplileptic drugs. In addition to use as an anti-seizure drug, Topamax is also used in preventing migraine headaches. Topamax (topiramate) is in a class of medications called anticonvulsants. Topamax is said to work by decreasing abnormal levels of excitement in the brain.

On March 4, 2011, the US FDA issued an FDA Warning citing the possibile serious birth defect side effects linked to Topamax use by women who are pregnant, including increased risk of serious congenital birth defects like cleft lip and cleft palate.

FDA: Risk of Oral Birth Defects in Children Born to Mothers Taking Topiramate (Topamax)

New data suggest that the drug Topamax and its generic versions (topiramate) increase the risk for the birth defects cleft lip and cleft palate in babies born to women who use the medication during pregnancy, the U.S. Food and Drug Administration said today.

Although at this specific point there is no official Topamax FDA Recall issued by the FDA, the posible strong link between Topamax and serious congenital cleft lip, cleft palate, cranio-facial and oral cleft birth defects has a significant number of medical professionals deeply concerned, and feeling that women who are pregnant should not be prescribed Topamax for any reason.

Women taking anticonvulsants, including Topamax (topiramate) — who are pregnant or thinking about becoming pregnant should speak with their doctor about the risks associated with Topamax or any other anti-seizure drugs while pregnant.

Topamax Information:

• Topamax Cleft Lip and Cleft Palate Lawsuit
• Topamax Recall
• Topamax and Spina Bifida
• Topamax Birth Defect Lawsuits
• Topamax Cleft Lip Lawsuits
• FDA Strengthens Topamax Birth Defects Warning
• FDA: Migraine Drug Topamax Ups Risk for Oral Birth Defects
• FDA Alert: Topamax Oral Clefts Risk in Infants
• Topamax Cleft Palate Lawsuits
• Topamax (Topiramate) – Birth Defects Update

Topamax Class Action Lawsuit vs. Individual Topamax Lawsuit

There are great differences between an individual Topamax (topiramate) cleft lip lawsuit and a Topamax (topiramate) cleft lip class action lawsuit.

In most all instances, a Topamax (topiramate) cleft lip lawsuit that involves severe birth injuries is better served by filing an individual Topamax (topiramate) cleft lip lawsuit. In an individual Topamax (topiramate) cleft lip lawsuit, the plaintiffs’ cases are filed and presented on their own merit, individually.

In class action Topamax (topiramate) cleft lip lawsuits, a group of victims typically are joined to form a “class”, which collectively brings a class action lawsuit against Ortho-McNeil Pharmaceutical LLC., and Johnson & Johnson (JNJ), the manufacturers of Topamax. All potential Topamax (topiramate) cleft palate plaintiffs would be grouped into a single Topamax (topiramate) cleft palate class action lawsuit, regardless of the severity of cranio-facial and oral cleft injuries. Topamax victims in a Topamax (topiramate) cleft palate class action lawsuit would then only share any resulting settlements or awards from the Topamax (topiramate) cleft palate class action lawsuit.

IOn the other hand, individual Topamax (topiramate) cleft palate lawsuits allow each Topamax (topiramate) cleft palate plaintiff to have their own individual case considered on an singular basis when damages, awards and settlement figures are considered. In individual Topamax lawsuits awards or settelments are based on an individual victim’s personal cleft palate injuries and future needs, and not as part of any grouped class action lawsuit.

Speak to a Topamax Lawyer

If you took Topamax (topiramate) or any other anti-seizure drug during pregnancy and your child was born with a cleft palate, cleft lip or any other congenital cranio-facial birth defect, please contact a Topamax Litigation Attorney at our law firm immediately. While it may be too late to recover from all of the devastating effects of Topamax, an experienced products liability pharmaceutical lawsuit lawyer at the Willis Law Firm can assist you in any legal action against Johnson & Johnson (JNJ) and Ortho-McNeil Pharmaceutical LLC, the makers of Topamax. You are not alone. Join other Topamax cleft palate and cleft lip birth defect victims and their families in speaking up and fighting for your legal rights.

Topamax Cleft Palate Lawsuit

Please fill out our free online legal evaluation form and we will contact you within 24 hours. Please keep in mind that certain states have statutes of limitation that limit the amount of time you have to file a lawsuit or seek legal action. Contact our law firm immediately so that we may explain the rights and options available to you and your family.

Common misspellings:
clef palate, cleff palate, cleft palite, clef palite, cleff palite, cleft pallite, clef pallite, cleff pallite, cleff pallate, clef pallate, cleff pallette, clef palette, topomax, topimax, tapomax, tipomax, tapamax

UPDATE:

FDA Strengthens Topamax Warning On Evidence Of Birth Defects

By Drew FitzGerald – DOW JONES NEWSWIRES | Friday March 4, 2011 12:45 PM EST

The U.S. Food and Drug Administration said it will strengthen warnings on the anti-migraine and anti-seizure treatment Topamax and its generic equivalents after new data suggested a higher risk for cleft palates in babies born to women taking the drug.

The move represents a setback for health-care products giant Johnson & Johnson (JNJ), which owns Topamax maker Ortho-McNeil Pharmaceutical LLC. The subsidiary last May pleaded guilty to promoting the drug for off-label uses and had to pay an $81.5 million fine.

The warning could also affect Vivus Inc. (VVUS), which is trying to get its weight-loss drug Qnexa to the market after the FDA asked for more information about its potential to cause birth defects. Qnexa is a combination of topiramate and the stimulant phentermine, which work together to reduce appetite and make the user feel more satisfied.

Shares of Vivus fell 7.8% to $6.50 Friday, while Johnson & Johnson shares were off 0.9% to $60.52 amid a broad market decline.

The FDA said Friday that data from the North American Antiepileptic Drug Pregnancy Registry indicated an higher risk of oral clefts in infants exposed to topiramate, the main ingredient in Topamax, during the first trimester of pregnancy. Infants exposed to topiramate as a single therapy had a 1.4% prevalence of oral clefts, compared with a 0.38% to 0.55% prevalence in those exposed to other antiepileptic drugs.

The regulator said health care professionals should warn patients of childbearing age about the drug ingredient’s hazard and said it will strengthen the warning on the drug’s labeling.

The new labeling will mean there is positive evidence of human fetal risk based on human data, but the potential benefits of the drug in pregnant women could sometimes outweigh the risks.

In a statement, Johnson & Johnson said it is working with the FDA to update the Topamax label and noted that the current prescription information already recommends cautious use in pregnant patients.

Topamax is used as an epilepsy treatment and as a preventative drug to prevent migraines before they start.

Speak to a Topamax Lawyer about a Topamax Lawsuit

If you took Topamax (topiramate) or any other anti-seizure drug during pregnancy and your child was born with a cleft palate, cleft lip or any other congenital cranio-facial birth defect, we encourage you to contact a Topamax Birth Defects Lawsuit Attorney at our law firm immediately. It may be too late to recover from all of the devastating effects of Topamax but an experienced products liability pharmaceutical lawsuit lawyer at the Willis Law Firm can assist you in legal action against Johnson & Johnson (JNJ) and Ortho-McNeil Pharmaceutical LLC, the makers of Topamax. You are not alone. Join other birth defect victims and their families in speaking up and fighting for your legal rights.

Please fill out our free online legal evaluation form and we will contact you within 24 hours. Please keep in mind that certain states have statutes of limitation that limit the amount of time you have to file a lawsuit or seek legal action. Contact our law firm immediately so that we may explain the rights and options available to you and your family.