Where do all the drugs go?

Ever wonder why meds get yanked from the market after supposedly being ruled safe by the FDA? I did. I remember using Bextra, with wonderful results, for really bad menstrual cramps for a few years…and then BAM! It was pulled from the market. Personally I was thinking “WTF?” I had used the medication for 4 years with no problems…no nausea or anything. So what could’ve possibly happened to make my miracle drug disappear like that? I know I’m not the only person this happened to. So what exactly happened? And why should anyone care?

Why do they make us sick if they’re supposed to be making us better?

Did you know that adverse drug reactions are one of the leading causes of death in the US?

Pharmocovigilance is the study of drug-related injuries used to make warning and withdrawal recommendations. In order to determine if there is a relationship between a medication and adverse reactions, the FDA looks at 5 things: 1) time relationships between usage of the drug and the reaction, 2) pathophysiology of the reaction, 3) any competing causes, 4) response to removal of the medication (dechallenge), and 5) response to reintroduction of the medication (rechallenge). If the FDA finds a relationship between the drug and the adverse reaction, they can then determine if the medication caused the adverse reaction. A medication can be considered the cause of the adverse reaction if, had the patient not taken the medication, 1) the reaction would not have happened, 2) the reaction would have happened later, or 3) the reaction would have been less severe. This information comes from the adverse drug event reports submitted by doctors, nurses, physician assistants, patients, and drug manufacturers.

In order for a drug to be termed as “safe” its usage benefits must outweigh the risks in the population the drug is intended to treat and for its intended usage. Over 75 medications have been withdrawn from the market due to safety questions in the last 10 years!

Drugs are pulled from the market based on the nature and frequency of adverse reactions and how the medication in question compares with other treatments out there. Most removals occur because the adverse reaction was not seen prior to wide distribution. Some adverse reactions are so rare that they can’t be seen or predicted before the medication is marketed. Other times there are hints that can be seen in retrospect, but they weren’t serious enough to necessitate the drug’s removal. Adverse reactions that occur 1 in 10,000 or 1 in 5,000 patients won’t be seen in clinical trials. Clinical trials are designed to look for “common” reactions that occur in 1 in 1,000 patients.

I bet you’re a little curious about those reactions. Well don’t worry…I’ve got two charts filled with big words to confuse you!

Drugs can be pulled off the market for a variety of reasons. The drug could be more toxic than expected, safer alternatives could become available, it could have too many dangerous drug interactions, or people could just be flat-out using it wrong. Very rarely is the decision made overnight though. Many times the manufacturer will try educating prescribers about safe usage or labeling changes. The drug can also be labeled as “second-line” or has it’s status restricted.

Watch this educational video, part of a series called The High Cost of Medication. This portion is about manipulation of clinical research and the role of the drug companies influencing the FDA.

Cox-2 Inhibitors

WHY COX-2 INHIBITORS WERE PULLED OFF THE MARKET

COX-2 Inhibitor drugs Vioxx (manufacturer Merck) and Bextra (manufacturer

Pfizer) were pulled off the market five years after being approved. The drugs showed evidence of increased risk of heart attack with use. Have you ever wondered why drugs like this were put on the market in the first place? Why the FDA didn’t catch the signs beforehand? This is alarming, due to the fact that an estimated 20 million individuals used the drugs during the 5 year course on the market. The New England Journal estimates a shocking 80 million population usage of Vioxx.

Vioxx: Reasons for getting pulled off the Market

COX-2 Inhibitor Vioxx showed little evidence in clinical trials to cause a great risk of heart attack. The drugs were approved and given to aid symptoms of osteoarthritis, acute pain, and menstrual pain. However, in 2004, five years after the initial trial, the VIGOR (Vioxx Gastrointestinal Outcomes Research) discovered evidence of cardiac toxicity. Merck voluntarily removed the drug from the market.[1] This conclusion was supported by three large, randomized trials: VIGOR, Merck, and The National Cancer Institute.[2]

The VIGOR trail “compared rofecoxib (50mg daily) with naproxen (500 mg twice daily) in 8076 patients with rheumatoid arthritis.” Subjects with recent cardiovascular events and those who were taking aspirin were excluded. The evidence of myocardial infarction showed to be five times as prevalent in the rofecoxib group as in the naproxen group.2 Similarly, the Adenomatous Polyp Prevention on Vioxx (APPROVe) trail, which ultimately led to the drug’s withdrawal, enrolled a relatively young group and excluded patients with recent ischemic cardiovascular disease.” Therefore, evidence of a high increased risk of myocardial infarction (heart attack) is confirmed with the clinical trail of young, healthy adults.[3] The Merck and National Cancer Institution presented similar data.

Bextra: Reasons for being pulled off the Market

Pfizer, Inc., manufacturer of Bextra (valdecoxib) was asked by the FDA to withdraw the drug in 2005. According to the Food and Drug Administration (FDA), Bextra showed an association “with an increased risk of serious adverse cardiovascular events in two short-term trails in patients immediately post-operative from coronary artery bypass graft surgery.”[4] The FDA based the withdraw request based on the following information:

• Lack of adequate data on cardiovascular safety of long-term use of Bextra, along with the increased risk of unfavorable cardiovascular events in short-term coronary artery bypass surgery (CABG) trials that FDA believes may be relevant to chronic use.
• Reports of serious and potentially life-threatening skin reactions, including deaths, in patients using Bextra. The reactions occurred in patients with and without prior history of sulfa allergy, and after both short and long-term use.
• Lack of demonstrated advantages for Bextra compared with other NSAIDs.[5]

Additionally, the FDA requested manufacturers of all markets prescription NSAIDs and COX-2 selective NSAID to review the package insert for their products, and include a boxed warning and a Medication guide. The boxed warning includes increased risk for cardiovascular disease and life-threatening GI bleeding. Even over the counter NSAIDs must include the revised labeling.

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[1] http://circ.ahajournals.org/cgi/content/full/113/18/2253

[2] www.nejm.org / A Lesson in Unexpected Problems

[3] http://circ.ahajournals.org/cgi/content/full/113/18/2173

[4] www.fda.gov/medwatch/report / Alert for Healthcare Professionals: Valdecoxib (marketed as Bextra)

[5] www.fda.gov/medwatch//report / FDA Public Health Advisory

What is IBS?

Irritable Bowel Syndrome (IBS)  is characterized by cramping, abdominal pain, bloating, constipation, and diarrhea. It can be very uncomfortable, so much that it can prevent people with IBS from working and participating in social events. About 20 percent of Adults suffer from this condition. To treat this condition, there have been many drugs that have been introduced. However, there are some serious consequences to the drug that outweighs the benefit of using an IBS drug. Zelnorm (tegaserod maleate) and Lotronex (alosetron) are two drugs I will discuss. I have posted a link to a website that provides some symptoms and causes of IBS. 

http://digestive.niddk.nih.gov/ddiseases/pubs/ibs/#what

Zelnorm

Zelnorm (tegaserod maleate) is a drug used to treat Irritable Bowel syndrome. It was withdrawn March 2007, due to high rates of heart attacks, strokes, and unstable angina. Thirteen treated patients had life-threatening cardiovascular adverse effects. It has also been linked with severe diarrhea and ischemic colitis.  In July 2007 it was back under Investigational New Drug (IND), in which the drug becomes available to patients who are seriously ill while the drug is being tested.

Only healthy women under the age of 55 can be eligible to receive the drug, who have IBS or chronic idiopathic constipation. Also, a patient is eligible if he/she has not had any problems with the drug before or did not respond to other medicines. The drug is made available at no cost to the user. This reduces the chance of the drug causing heart attacks and strokes. Therefore, it may be resubmitted in to the FDA and only be approved for healthy women under 55.

As of April 2008, the company Normis, which produces Zelnorm, has decided to shut down the program and making Zelnorm unavailable for anyone, regardless of situation. It took eight months for the company to decide to remove the drug from the public? This means that within those eight months, who knows how many people have taken this drug and risked their life? The company has made this info available on their website.

http://www.zelnorm.com/index.jsp

Lotronex

Lotronex (alosetron) is a drug used for diarrhea predominant IBS that was approved in February 2000 but withdrawn that same year because it was linked to ischemic colitis. However it was made available again in 2002 under a “risk management program.” The drug had caused 100 hospitalizations, 50 surgeries, and 7 deaths, and yet it was still made available.  

Again the drug was only made available for women under 55 who are healthy and have no other risk factors like cardiovascular related diseases. The company has not performed clinical studies that would confirm any benefits for men. Physicians that are prescribing the drug must be a member of the Prescribing Program for Lotronex (PPL). Under the PPL, the physician must be aware of the prescribing information, what the drug is used for, and know the risks involved. The patient must be given a Medication Guide that has all the information on the drug including the risks involved.  The physician must also explain the risks to the patient and sign a form stating they have done this and the patient must sign a consent form. The patient must be told not to take the drug if constipated, to stop taking the drug if they become constipated and call their doctor. Also, the patient must be told not to resume taking the drug afterwards. The company’s website provides in depth information of the drug from risk factors and prescribing guidelines. There is also, information regarding the gastrointestinal adverse effects associated with the drug and the symptoms of the most common ones. You can even find the very detailed prescribing information that states, the dosage and even how to begin treatment. The link will be posted at the end of this portion.

http://www.lotronex.com/Patients/

So what did we learn?

In finding these drugs, it really opened my eyes!  How easy it is to allow dangerous drugs to be available to patients! It is a serious loophole and the FDA allows it. A drug can be revoked, but still made available under these loopholes. Even with significant data that shows how serious the adverse effects are, patients are still allowed to take them! In the Zelnorm case, it was the COMPANY that decided to completely remove the drug and not the FDA! Even so, there was an 8 month period in which the drug was still available. It was even free! The drug should have been removed as soon as they found out that it can cause strokes, heart problems, and even death! Lotronex, however, is still being used. It is a very dangerous drug that puts a lot of responsibility on the patient. Do they really expect a patient to read the whole manual? It is very long and has a lot of information. Most patients are like “Yea ok give me the drug now!” The patient has some responsibility in making sure what goes into their body, but it is also irresponsible to make a drug available that can cause so many life-threatening complications!

I don’t know about you, but I would rather have some cramping and bloating than a heart attack, losing parts of my bowel, or losing my life!

Litigation Surrounding Baycol

What is Baycol?

 

It is a statin, a cholesterol lowering drug, produced by Bayer. It was approved in 1997 by the FDA.

 

What were the major problems associated with the drug?

 

Baycol was associated with rhabdomyolysis which is muscle cell degeneration that may lead to fatal organ damage. When this occurs, muscle cells break down and cause serious problems. This can be fatal to patients who experience it. In August of 2001, the FDA received a great number of reports claiming that people taking the drug were experiencing rhabdomyolysis. The numerous claims were enough to necessitate a Baycol recall. 

 

Why was Baycol removed from the market?

 

On August 8, 2001, a recall was issued for Baycol as there were 700,000 people in America taking the drug at the time. After 32 deaths due to fatal rhabdomyolysis, Bayer withdrew from the market. There were over 100 deaths caused by rhabdomyolysis in the US after patients were prescribed the drug, which was the foundation of many lawsuits. The recall was due to the increased risk of rhabdomyolysis in patients who took the drug as opposed to other statins. Information regarding the Baycol recall indicated that Bayer may have known that their drug caused a significantly increased rate of rhabdomyolysis for over a year before they added the warning to the label. Court documents demonstrated that despite the fact that the company was aware of the severe and fatal side effects, executives continued to promote the drug as safe and effective.

 

 

Increasing amount of lawsuits involving Baycol: Bayer facing one of the largest product liability cases

 

Once Baycol was removed from the market in August 2001, an increasing number of cases were filed against Bayer as many claimed that Bayer continued to market Baycol as safe and effective after numerous reports of serious side effects such as rhabdomyolysis. Because of the high number of people who failed to report side effects initially, the number of cases against Bayer has increased. More than 12,000 Baycol lawsuits were filed after the recall.

 

How did Bayer settle the cases?

 

Bayer has spent millions of dollars settling cases. As of May 2003, Bayer claimed they had spent an estimated $240 million on settling 785 Baycol cases. There are still 9,400 pending cases against the makers of Baycol that have yet to be settled. The Kaiser Daily Health Policy report stated on November 23, 2004 that Baycol has settled approximately 2,861 injury cases involving the drug. Baycol has settled 888 lawsuits as on June 10, 2003. May 2004, Baycol cases settled approximated 2,312 for $872 million. Bayer AG stated that they had paid $1.133 billion to settle 2,995 cases worldwide as of April 25, 2005. That is an estimated average of $381, 224 per case.

 

 

What do the experts say?

 

The Plaintiff’s Steering Committee (PSC) issued the statements of experts in various medical areas which provided the foundation and evidence on behalf of the patients injured from taking Baycol.

 

Richard M. Kapit, M.D. He worked for the Government of the United States including 16 years as a clinical reviewer at the FDA. He stated that, “Bayer’s knowledge of the excessive toxicity level of Baycol, the FDA’s reliance on full and honest disclosure, reckless disregard for public health by Bayer, misplaced trust and Bayer’s priorities and company strategy for Baycol.”

 

Bruce M. Carlson, M.D., Ph.D. He is a Professor in the Department of Cell and Developmental Biology at the University of Michigan Medical School. “Carlson reports that Baycol led to higher incidence of muscle problems than the other statins on the market. He explains the continuum of harm at the level of both individual muscle fiber and the entire muscle.”

Christopher P. Chengelis, Ph.D., D.A.B.T. He is a consultant in toxicology and provides technical services to companies that develop pharmaceutical products for market. “His conclusions find that Bayer consistently attempted to gain FDA approval, rather than conduct proper due diligence to assess safety. In fact, it was clear to Dr. Chegnelis that Bayer did not act in a scientifically appropriate manner by heeding the warning signs as evidenced by the findings from its preclinical studies.”

 

www.baycolpsc.com

www.adrugrecall.com

 

 

 

 

 

Litigation Surrounding Bextra

 

What is Bextra?

 

It was approved by the FDA in November 2001 to treat pain associated with osteoarthritis, rheumatoid arthritis, and primary dysmenorrheal. It is a COX-2 inhibitor that is manufactured by Pfizer.

 

What were the major problems associated with Bextra?

Since the recall of a similar COX-2 inhibitor, Vioxx, there was increasing concern over the safety of all other COX-2 inhibitors on the market. Bextra is known to cause a deadly skin disease called Stevens-Johnson syndrome as well many other common side effects such as: epidermal necrolysis, severe allergic reactions, indigestion, headache, stomach pain, nausea and diarrhea. Bextra can also cause serious and deadly side effects such as: skin conditions, heart attack, stroke, blood clots, renal failure, GI complications and heart failure.

Why was Bextra removed from the market?

After serious side effects were discovered, the FDA asked Pfizer to increase Bextra warning on their label in 2002. Despite this action, Pfizer failed to comply. Pfizer also failed to inform Bextra users after they knew the cardiovascular risks. On April 7, 2005, after the FDA had requested, Pfizer stopped all sales of Bextra in the U.S. The deadly risks of the drug no longer outweighed the potential benefits. The public citizen consumer group strongly urged the FDA to ban Bextra on January 24, 2005. In that same month, data linked Bextra to an increased risk of stroke and heart attack. “Black box” warnings were requested to be placed on Bextra once news of the cardiovascular side effects emerged.

Lawsuits involving Bextra

 

Despite many of the FDA warnings, Pfizer continued to market drugs that were known to cause serious and deadly side effects. The company’s failure to comply with the FDA to inform patients about the dangers of Bextra has led to an multiple claims against the pharmaceutical company. Pfizer even refused to add warning labels on Bextra and continued to market the drug as safe, despite that deadly side effects were reported. This supports legal class action lawsuits that claim Pfizer knowingly sold and advertised a drug that was dangerous to consumers. As stated under product liability legal statutes, companies must be held responsible for any damages caused by their product if they continue to supply a drug that is defective.

 

Case involving Rita Fohne

Rita Fohne took Bextra for 6 months and suffered major cardiovascular injuries due to thrombosis and blood clots. In this lawsuit, Bextra was dangerously defective and the side effects definitely outweighed the benefits of the drug. Fohne claims that Pfizer knew of the risks of this drug but continued to market it due to financial motivation. She also claimed that the pharmaceutical company did not warn doctors of the serious effects of the drug. She sought $250,000 in damages. Pfizer defended its product. In the case, a panel of doctors and scientists advised that Bextra remain on the market despite the fact that most members of the panel said the drug should carry a black box warning. The FDA did something out of the usual and went against the panel, claiming that Bextra’s risks outweighed the benefits and it should be removed from the market immediately. Litigation threats remain since Pfizer defended the drug as safe and effective.

www.adrugrecall.com

www.onlinelawyersource.com

 

 

Litigation Surrounding Vioxx

What is Vioxx?

           

Vioxx was approved by the FDA for use in May 1999. It was approved to reduce the signs and symptoms of osteoarthritis as well as dysmeonorrheal and acute pain.

 

What were the major problems associated with Vioxx?

 

Several prominent medical journals have suggested that Vioxx use increases the risk of heart attack in patients who have taken the drug for over a year. Patients who have taken the drug for around 18 months had a significantly higher instance of heart attack and stroke. There are other less serious side effects, but the increased risk for heart attack and stroke is the main force behind the FDA’s recall of the drug.

 

Why was Vioxx removed from the market?

           

In 2004, a test was developed to show that Vioxx could reduce colon polyps. This test, however, showed that Vioxx use were twice as likely to suffer from a heart attack or stroke as opposed to those who received a placebo in the study. That September, Merck voluntarily recalled Vioxx from the market. The FDA ordered it to be removed from the market after studies demonstrated that those who took the drug were more likely to suffer from heart attacks and stroke. From 1999-2003, Vioxx was linked to approximately 27,000 heart attacks or deaths from cardiac problems in the US. Steven Galson, the director of the FDA’s Center for Drug Evaluation and Research, stated “We have been concerned and aware of the potential for cardiovascular effects for the last few years…this is not a total surprise.”

 

Lawsuits involving Vioxx

 

Lawyers have accused Merck of being aware of the damages their drug Vioxx has caused patients receiving the drug. They have accused Merck of withholding important information about the drug from patients as well as physicians. Since 2003, 27,000 cases were filed by 47,000 plaintiffs against Merck. There have been 265 class action lawsuits by states who want to recover money spent on the drug. The company spent an estimated $160 million in one quarter, not including the cost to cover damages.

 

$45 million lawsuit: In Atlantic City, New Jersey, a jury found Merck accountable for a man who suffered from a heart attack who had been taking Vioxx. He was awarded $4.5 million in damages. The New Jersey state jury also found that the company failed to alert John McDarby, 77, and his health care provider about the risk factors causing cardiac problems. Thomas Cona, 60, was also included in the trial. He also claimed that Vioxx was the cause of his heart attack, however, the jurors ruled that Vioxx was not responsible. He was only awarded $45 for compensation for his medication. Both lawyers accused Merck of rushing the drug into the market without investigating the cardiac complications it caused.

Former FBI agent wins $51 million case: A jury found that Vioxx, a drug produced by Merck, was the cause of Gerald Barnett’s heart attack. This case was tried in New Orleans federal court where Barnett, a 62 year old former FBI agent, claimed that Merck’s drug Vioxx was the cause of his 2002 heart attack. This verdict will make it hard for the pharmaceutical company to go to trial for each of the thousands of individual cases filed.

 

How did Merck settle the cases?

 

Merck agreed to pay $4.85 billion to settle claims for those who suffered heart attacks associated with Vioxx and $850 million for those who suffered from stroke. Despite this large amount, the money received by each plaintiff will vary greatly and Merck is still undecided about how many people this amount of money will cover. Merck decided to do this instead of fighting case-by-case lawsuits.

 

http://www.expertlaw.com

http://www.msnbc.msn.com

http://www.consultwebs.com

http://www.newsinferno.com

www.fda.gov

www.ryar.org