Drug Injury Watch

Digitek Lawsuits Filed In Federal Court Sent To The Southern District Of West Virginia

Judge Joseph R. Goodwin Will Preside Over "Double-Dose" Digitek Pill Cases Pursuant To MDL Litigation Order

(Posted by Tom Lamb at DrugInjuryWatch.com)

On August 13, 2008 the Judicial Panel on Multidistrict Litigation (JPMDL) issued an order creating the Digitek products liability multidistrict litigation, In Re: Digitek Products Liability Litigation, MDL No. 1968, JPMDL. Further, the JPMDL assigned the Digitek multidistrict litigation, or MDL, to Judge Joseph R. Goodwin, of the U.S. District Court for the Southern District of West Virginia.

As you may recall, in late April 2008 the FDA announced that Digitek (digoxin tablets) manufactured by Actavis Totowa LLC at its Little Falls, New Jersey plant was the subject of a nationwide Class I recall because of the possibility that some tablets were manufactured such that they contained twice the approved level of active ingredient.

Furthermore, on August 1, 2008 Actavis Totowa LLC announced a recall of all generic drugs manufactured at its Little Falls plant, apparently due to a lack of good manufacturing practices (GMP) and/or a lack of quality control at this particular New Jersey facilty.

At the time of the JPMDL hearing in late July 2008 concerning the issue of whether a federal court Digitek MDL was necessary, there were at least 60 lawsuits which had been filed against Actavis Totowa, LLC and Mylan Pharmaceuticals, Inc., as well as numerous other corporate entities related to Acatavis and Mylan.

In the August 2008 Transfer Order for the Digitek MDL, Judge John G. Heyburn II, chairman of the Panel on Multidistrict Litigation, wrote:

On the basis of the papers filed and the hearing session held, we find that the actions in this litigation involve common questions of fact, and centralization… in the Southern District of West Virginia will serve the convenience of the parties and witnesses and promote the just and efficient conduct of the litigation. All actions share factual questions relating to the manufacture and sale by defendants of allegedly adulterated Digitek, which was recalled in April 2008.

Since July 2008 additional Digitek lawsuits have been filed in federal courts and various state courts around the country, and a great number more Digitek personal injury and wrongful death case filings are expected in the months to come.

Teva's Budeprion XL Will Get Another Safety And Efficacy Review By FDA

FDA To Collaborate With Complaining Patients On Study Of Reported Problems With This Generic Version Of Antidepressant Wellbutrin XL

(Posted by Tom Lamb at DrugInjuryWatch.com)

By means of a September 23, 2008 Wall Street Journal (WSJ) article, "Wellbutrin Generic to Get New Review", we learned that the FDA is going to re-visit the issues of whether Budeprion XL -- which is made by Impax Laboratories Inc. and distributed by Teva Pharmaceutical Industries Ltd. -- is as safe and effective as Wellbutrin XL -- made by Canada's Biovail Corp. and sold by GlaxoSmithKline PLC.

From the September 23 WSJ article by Andy Georgiades:

Five months after declaring a generic version of antidepressant Wellbutrin XL safe, the U.S. Food and Drug Administration says it is prepared to conduct a human trial to get to the bottom of consumer complaints about the drug....

More than 100 complaints about the drug were filed with the FDA between December 2006 and the end of this January. Among the most common complaints were that the drug was ineffective or aggravated the condition, or caused nausea, anxiety or headache.

This past summer, [Joe Graedon, a pharmacologist and co-founder of the People's Pharmacy] and others were granted a meeting with senior officials from the FDA's Center for Drug Evaluation and Research.

Mr. Graedon said there was a "consensus" by the end of the meeting that the two sides could collaborate on a study that would involve patients who reported problems with the generic after taking the branded version. But he can't begin a recruitment effort until he is given the details of the study design, and he is still waiting to hear from the FDA on that.

This September 2008 WSJ article about generic Wellbutrin reminded me of a man who contacted me in mid-August 2008 regarding an "extreme reaction" -- he said the ultimate diagnosis was septic shock -- which he had within an hour of ingesting his first dose of Budeprion XL.  Taken to the ER, he was put into the Intensive Care Unit (ICU) for several days, and was hospitalized for more than a week until his condition stabilized.

After taking Wellbutrin XL for years without any problem, this man could not understand why Budeprion, which was "only" the generic version of Wellbutrin, would produce this suspected (by his doctors) serious side effect.

Then he found online this article, "Are Generic Drugs Safe?", by Joe Graedon, MS, and Teresa Graedon, PhD; it was published originally in the February 2008 edition of Prevention magazine, which he forwarded to me.

In relevant part, from this February 2008 Preventionarticle by the Graedons:

On March 20, 2007, we contacted the FDA with our concerns; both Robert J. Temple, MD, director of the Office of Medical Policy at the Center for Drug Evaluation and Research, and Gary J. Buehler, RPh, director of the Office of Generic Drugs, told us that the agency would look into it. But the FDA moves slowly, and we were anxious to get to the bottom of this, so we teamed up with ConsumerLab.com to take a close look at Wellbutrin XL 300 and its equivalent, Budeprion XL 300, as well as two generics for sustained-release Wellbutrin. (Most generics go by the name of the active ingredient--in this case, bupropion hydrochloride. But some, like Budeprion, are given distinctive names.) ConsumerLab.com bought samples of each drug to test, using two labs to double-check the results.

You can read about what was found-out by the ConsumerLab.com testing team when you read the Prevention article, which I recommend if you are truly interested in this subject.

We will watch for more about the FDA study comparing Budeprion to Wellbutrin in terms of safety and efficacy, as well as continue to monitor other emerging generic drug issues such as quality control, good manufacturing practices (GMP), and the like.

It seems -- from Actavis Digitek pills and Ethex morphine pills being double-the-intended-dose in some instances, to this current alleged problem with Budeprion -- we should not blindly accepted the "pitch" from health insurance companies that the generic drugs they want you to take, now, are just as good as the brand name medications that they switched you from for cost reasons.

Association Between Long Term Fosamax Use And Femoral Stress Fracture Is Challenged

September 2008 ASBMR Meeting: Dr. Abrahamsen Asserts Atypical Fractures Of Femur Are Not Triggered By Fosamax

(Posted by Tom Lamb at DrugInjuryWatch.com)

In late June 2008 we learned that one type of femoral stress fracture (simple, transverse) may be caused by long term use of the popular bisphosphonate Fosamax.  Drs. Dean G. Lorich and Joseph M. Lane of NewYork-Presbyterian Hospital/Weill Cornell Medical Center presented information about this possible new Fosamax side effect in the latest issue of the Journal of Orthopaedic Trauma.

About three months later, however, a Danish researcher said said that such atypical fractures of the femur do not appear to be triggered by Fosamax (alendronate).

In more detail, in mid-September 2008 at the American Society for Bone and Mineral Research (ASBMR) meeting in Montreal, Bo Abrahamsen, Ph.D., of Copenhagen University Hospital Gentofte, asserted that patients treated with the anti-osteoporosis drug Fosamax apparently had a higher risk of these atypical fractures (as well as fractures of any kind) to start with for the simple reason that they were taking a drug known to reduce the risk of hip fractures.

For elaboration on Dr. Abrahamsen's position we turn to the September 15, 2008 Medpage Today article, "ASBMR: Alendronate Exonerated in 'Atypical' Femoral Fractures":

The three case reports earlier this year suggested that a common factor in patients with subtrochanteric or proximal diaphyseal fractures of the femur is [Fosamax]use, Dr. Abrahamsen said.

But those reports did not have any comparison data, he said. "The real problem is the denominator -- you don't know how common this is," he said.

It's especially important to know how common such fractures are in comparison with hip fractures, Dr. Abrahamsen said, in order to understand the risks and benefits of the treatment.

To help fill the gap, he and colleagues looked at registry data for all patients born 1945 or earlier who arrived at Danish hospitals with fractures from 1996 through 2005....

He concluded that the atypical fractures are "best classified" as osteoporotic fractures and added that there's no evidence that use of [Fosamax] increases the risk of the atypical broken bones.

More facts in support of Dr. Abrahamsen's position can be found in the primary source for his September 2008 ASBMR presentation, "Subtrochanteric And Diaphyseal Femur Fractures in Patients Treated with Alendronate: A Register-Based National Cohort Study", by Abrahamsen B, et al, which was published in Journal of Bone Mineral Research (JBMR 2008; 23: Abstract 1026).

FDA: Tequin Was Withdrawn From U.S. Market "For Reasons Of Safety Or Effectiveness"

Recall That Bristol-Myers Had Said Decline In Sales Was Reason For Its Decision To Stop Selling Tequin

(Posted by Tom Lamb at DrugInjuryWatch.com)

On September 2, 2008 the FDA issued a Notice entitled "Determination That TEQUIN (Gatifloxacin) Was Withdrawn From Sale for Reasons of Safety or Effectiveness" which provides (and confirms) the real reason that Bristol-Myers Squibb Co. (BMY) decided to pull Tequin from the U.S. market in the spring of 2006:

SUMMARY: The Food and Drug Administration (FDA) has determined that TEQUIN (gatifloxacin) Tablets, Injection, and Oral Suspension, were withdrawn from sale for reasons of safety or effectiveness. This determination means that FDA will not accept or approve abbreviated new drug applications (ANDAs) for gatifloxacin oral tablets, injection, or oral suspension that refer to any previously approved dosage forms and strengths of TEQUIN (gatifloxacin).

As you may recall, in April 2006 when the news first broke that Bristol-Myers had decided to stop selling Tequin -- an antibiotic which was increasingly associated with potentially fatal blood-sugar problems -- the drug company said a continuing decline in Tequin sales was its reason for deciding to stop selling Tequin.

In turn, on May 1, 2006 the consumer advocacy group Public Citizen submitted a petition asking the FDA to ban Tequin in order to have this unsafe drug removed from pharmacy shelves immediately, as opposed to the gradual withdrawal announced by Bristol-Myers.

Now, more than two years after the Public Citizen petition about Tequin was submitted, we have the FDA's final word on the real reason that Tequin was taken off the market:

After considering the citizen petition and reviewing agency records concerning the drug product, analyses of AERS reports, and relevant literature, FDA has determined under Sec.  314.161 that TEQUIN was withdrawn from sale for reasons of safety or effectiveness.

This FDA determination seems to confirm earlier suspicions that, by going the course of a gradual withdrawal as opposed to a Tequin recall, BMS -- as it did with the now withdrawn anti-depressant Serzone -- was trying not to draw any additional attention to (or "hide" one might say) Tequin's safety problems. 

So much for candor from Big Pharma.

P.S.  For an in-depth review of various other issues concerning Tequin, you should read Armand Rossetti's September 11, 2008 post "The Tequin Mystery".  (9/11/08) 

New Reports Of Vytorin And Zetia Causing Liver Failure And Liver Disease

2008 Medical Journal Articles Describe Two Cases; Authors Suggest Liver Testing At Start Of Therapy And When Titrating Dosage Is Necessary

(Posted by Tom Lamb at DrugInjuryWatch.com)

In December 2007 we told you about an article by New York Times (NYT) reporter Alex Berenson, "Data About Zetia Risks Was Not Fully Revealed", which revealed that Merck and Schering-Plough had conducted several studies of Zetia that raised the possibility that Zetia can cause liver damage when used long-term with statin drugs.  The drug companies, however, decided not to publish the results of those Zetia studies, according to this NYT article.

Now, in late summer 2008, two medical journal articles have been published which associate Zetia (ezetimibe) with liver failure and liver disease.

From the September 1, 2008 edition of Pharmacotherapy we get an article, "Simvastatin-ezetimibe-induced hepatic failure necessitating liver transplantation", that discusses a case of liver failure involving Vytorin -- which is a combination of Zetia with the statin drug Zocor.  The article points out that reports liver damage reports involving Zetia or Vytorin have not been widely published to date.  It continues with one particular case report involving liver failure in a patient using Vytorin.  From the abstract from this August 2008 Pharmacotherapy article:

We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin [or Zocor] 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day [i.e., Vytorin]. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. [The Vytorin] and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course....  To our knowledge, this is the first case report of [Vytorin]-induced liver failure that resulted in liver transplantation.

Thereafter, the article authors -- from the Division of Clinical and Administrative Pharmacy, at University of Iowa's College of Pharmacy -- posit a theory on how Vytorin and Zetia can cause liver failure:

[Zetia] undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity....  We postulate that the mechanism of the [Vytorin]-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes.

These authors conclude with the suggestion that liver function tests should be carefully monitored when starting Vytorin therapy and when titrating the Vytorin dosage.

The second article, "Serious drug-induced liver disease secondary to ezetimibe", published in World Journal of Gastroenterology, August 28, 2008 edition, focuses on just Zetia.  It reports the case of a woman who developed a "serious hepatocellular drug-induced liver disease" after taking Zetia 10 mg daily for a four month period, then recovered after she was taken off the Zetia.  Based on this case, the authors concluded:

[Zetia] may produce serious toxic hepatitis and prompt withdrawal is mandatory in case of a significant abnormality in liver testing after beginning or during treatment with [Zetia].

We will continue to watch for reports of liver injury associated with Vytorin and Zetia.  If you are aware of such a case, please share your information with us.