Drug Injury Watch

Diabetes Drug Avandia Associated With Liver Injury And Liver Failure, Again

July 2009 Medical Journal Article Follows 2008 Public Citizen's Petition For FDA To Ban Sales Of Avandia In U.S.

(Posted by Tom Lamb at DrugInjuryWatch.com)

In October 2008 Public Citizen petitioned the FDA to ban the sale of the diabetes drug Avandia (rosiglitazone) in the U.S. because its risks, which include heart attack and heart failure in addition to liver toxicity, far outweigh its benefits and because much safer alternatives exist for treating Type 2 diabetes.

To our knowledge, there has been no word from the FDA, yet, about how long the agency will need to make a determination on the Avandia recall requested by Public Citizen.

In late July 2009, however, a new medical journal article about Avandia and liver failure was published in Pharmacoepidemiology and Drug Safety.

This article, "Case series of liver failure associated with rosiglitazone and pioglitazone."-- by James S. Floyd, MD, Elizabeth Barbehenn, PhD, Peter Lurie, MD, MPH, and Sidney M. Wolfe, MD, of Public Citizen's Health Research Group -- seemingly adds further support to the contention that Avandia can cause death from liver failure and should be banned immediately by the FDA.

In more detail, the study found 11 cases of severe liver toxicity, mostly fatal, related to using Avandia. Those cases were identified after careful analysis of MedWatch forms submitted between 1997 and 2006 to the FDA’s Adverse Event Reporting System (AERS).

From a July 22, 2009 press release, "Rigorous Study Adds to Case That FDA Should Ban the Diabetes Drug", which was issued by Public Citizen in connection with this new Avandia medical journal article, we get these points:

• "Because of low reporting rates to the AERS database, the 11 cases likely represent a small fraction of patients who developed liver failure because of the drug," said Dr. James Floyd, a Public Citizen health researcher and lead author of the study. "Our best estimate is that one case of liver failure occurs for every 44,000 patients who take Avandia."

• "The research is yet another indication that Avandia is too dangerous to remain on the market," said Dr. Sidney Wolfe, acting president of Public Citizen, director of Public Citizen’s Health Research Group and co-author of the study. "The FDA’s new leadership should demonstrate its commitment to public health by banning this drug, thereby preventing needless deaths and serious adverse events."

• In 2006, the number of prescriptions filled for the drug peaked at 13.2 million. That number dropped to 3.1 million in 2008. This means that about 8,500 prescriptions a day are still being filled for this dangerous drug.

To date, most of the drug injury litigation concerning Avandia has involved cardiovascular adverse reactions such as heart attacks and strokes.

Conversely, it is not widely known that Avandia can be "hepatotoxic", meaning that it can cause liver injury accompanied by hepatic encephalopathy or liver failure, and in some instances require liver transplantation.

We are currently investigating cases where there has been possible Avandia-induced liver damage as potential drug injury lawsuits.

First Fosamax Trial In Federal Court MDL Will Start As Scheduled On August 11, 2009

Judge Keenan Denies Merck's Summary Judgment Motion, But Rules That Merck Will Not Face Possible Punitive Damages In This Case Involving Shirley Boles

(Posted by Tom Lamb at DrugInjuryWatch.com)

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UPDATE:  Boles v. Merck Fosamax Trial Jury Verdict Is $8 Million For Plaintiff In June 2010

UPDATE:  "Merck lawsuit over Fosamax ends in mistrial"  (9/11/09)

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According to a July 29, 2009 Bloomberg article, "Merck Won’t Face Punitive Damages in Fosamax Trial":

U.S. District Judge John Keenan said at a hearing today in New York that he’ll release a decision as early as July 31 knocking out the possibility of punitive damages in the case. He’ll deny Merck’s request to rule in its favor on liability, which means the case will go to trial Aug. 11, he said.

"I am not granting summary judgment on anything else," Keenan said.

Keenan has scheduled three so-called bellwether trials through January to show each side the other’s strategy and possibly point the way to settlements....

At the present time, about 700 Fosamax lawsuits filed in the federal court system have been consolidated in In Re Fosamax Products Liability Litigation, MDL 1789, U.S. District Court, Southern District of New York (Manhattan), with Judge Keenan presiding.  This consolidation of Fosamax cases is commonly referred to as the Fosamax MDL -- short for multi-district litigation.

This first Fosamax trial in the federal court Fosamax MDL involves Shirley Boles, 71, of Walton Beach, Florida, who used Fosamax from 1997 to 2006 and eventually developed osteonecrosis of the jaw (ONJ), which has been described as jawbone tissue death.

As regards the legal theory being presented by the plaintiff in this Boles case, according to the July 29 Bloomberg article;

[Plaintiff Boles] argues Merck had a duty to change the Fosamax label to warn doctors about a connection to the disease as early as the mid-1990s. She also said her condition worsened because the company’s failure to warn meant she kept taking the drug.

Merck and Boles disagree about when she was diagnosed with the condition. [Judge] Keenan said today the evidence showed "she developed her injury by September 2003 at the latest" and [Judge Keenan] won’t allow evidence about Merck’s conduct after that date.

The same Bloomberg article also re-caps the most recent (albeit a bit dated) information about the extent of this ongoing Fosamax litigation:

• Merck, which is buying rival Schering-Plough Corp., had a reserve of about $24 million for the litigation, including lawyers’ fees, as of March 31, having spent $9 million on the cases in the first quarter, the company said in May. It hasn’t set aside any money to pay damages, it said.

• As of March 31, Merck faced about 856 Fosamax cases, including suits with multiple patients, in state and federal court, the company said. About 700 of the lawsuits have been consolidated before Keenan in New York federal court for evidence-gathering. About 130 cases are before Judge Carol Higbee in state court in Atlantic City, New Jersey, Merck said.

By comparison, at about this time last year 655 Fosamax lawsuits had been filed against Merck.

We will be watching closely this first Fosamax trial in the federal court MDL, Boles v. Merck, as well as the second and third bellwether cases, Fleming v. Merck -- currently set for trial on October 27, 2009 -- and Greene v. Merck -- which is scheduled to begin January 11, 2010.

P.S.  "Statement by Merck & Co., Inc. Regarding FOSAMAX® (alendronate sodium) and Rare Cases of Osteonecrosis of the Jaw" issued July 29, 2009.  (7/30/09)

P.S.  On September 2, 2009 Judge Keenan rescheduled the trial of Bessie Fleming v. Merck & Co. Inc., No. 1:06-cv-07631-JFK, to start on January 5, 2010, instead of the date previously scheduled, December 1, 2009.  In addition, the trial of Louise H. Maley v. Merck & Co. Inc., No. 1:06-cv-04110-JFK, will commence on April 19, 2010, instead of the date originally scheduled, January 11, 2010.  (9/3/09)

P.S.  From a Dow Jones article, "Judge Dismisses Second Case Involving Merck's Fosamax", published on November 24, 2009 by The Wall Street Journal:

NEW YORK—A federal judge dismissed the second of three so-called "bellwether" cases over Merck & Co.'s osteoporosis drug Fosamax.

In an order Monday, U.S. District Judge John F. Keenan in Manhattan granted Merck's request for summary judgment in a product-liability case brought by Bessie Flemings, a 74-year-old Mississippi woman who claims she developed a severe jaw condition, known as osteonecrosis, as result of taking Fosamax....

(11/24/09)

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DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects

Yasmin / YAZ Multidistrict Litigation (MDL) Motion Filed Late July 2009

Requests Consolidation Of Federal Court Lawsuits Alleging Yasmin Or YAZ Caused Injury Such As Stroke, Heart Attack, Pulmonary Thrombosis, Deep Vein Thrombosis, And Death

(Posted by Tom Lamb at DrugInjuryWatch.com)

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Update:  On October 1, 2009 the JPML filed a Transfer Order to the effect:  MDL No. 2100 -- IN RE: Yasmin and Yaz (Drospirenone) Marketing and Sales Practices and Products Liability Litigation -- Assigned To Southern District of Illinois  (10/1/09)

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Update:  According to a Notice of Hearing Session issued August 14, 2009 by the U.S. Judicial Panel on Multidistrict Litigation (JPML), there will be a hearing on September 24, 2009 regarding this YAZ and Yasmin MDL Motion.  At this hearing the JPML will consider whether all current, as well as all future, YAZ and Yasmin drug injury cases filed in the federal court system should be consolidated as an MDL and, if so, to which U.S. District Court Judge the YAZ / Yasmin MDL litigation should be assigned.  (8/14/09)

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On July 24, 2009 the United States Judicial Panel on Multidistrict Litigation (JPML) in Washington, D.C. received a motion requesting that all Yasmin and YAZ product liability lawsuits filed in the federal court system across the country be consolidated and transferred to Chief Judge James G. Carr of the United States District Court for the Northern District of Ohio.  Put otherwise, the motion asks for the creation of a Yasmin / YAZ MDL -- which is short for "multi-district litigation".

According to the Yasmin / YAZ MDL motion papers, as of July 24, 2009 there had been at least 32 lawsuits filed in federal courts around the nation on behalf of women alleging that their use of the relatively new birth control pills Yasmin or YAZ caused serious personal injuries including deep vein thrombosis, pulmonary embolism, heart attack, stroke, kidney failure, seizures, gall bladder injuries, and death.

The companies which have been commonly named as Defendants in these federal court Yasmin and YAZ lawsuits include:

Bayer Corporation;
Bayer Healthcare Pharmaceuticals, Inc.;
Bayer Healthcare, LLC; and,
Berlex Laboratories International, Inc.

Next, the JPML will consider the motion papers and hold a hearing to determine whether the current lawsuit situation supports the creation of a Yasmin / YAZ MDL for all personal injury and wrongful death cases filed in the federal court system.  At present, the hearing date for this Yasmin / YAZ MDL motion is unknown.

You can learn more about these lawsuits by visiting the YAZ, Yasmin, Ocella, Gianvi, and Zarah Information Page over on our Drug Injury Law web site.

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DrugInjuryLaw.com: Legal Information And News About Prescription Drug Side Effects

A Summary Of Inpatient Cardiovascular Medication Error Reports Involving Children

July 2009 Pediatrics Medical Journal Article Finds Most Cases Involved Infants Less Than One Year Of Age

(Posted by Tom Lamb at DrugInjuryWatch.com)

The article "Cardiovascular Medication Errors in Children" was published in the July 2009 edition of the medical journal Pediatrics.

The authors of this article had two basic aims: (1) to describe pediatric cardiovascular medication errors; and, (2) to determine patients and medications with more-frequently reported and/or more-harmful errors.

For their research, the authors analyzed cardiovascular medication error reports from the US Pharmacopeia MEDMARX database from 2003–2004 for patients no older than 18 years of age.

From the Abstract for this July 2009 Pediatrics article we get their findings:

RESULTS:  A total of 147 facilities submitted 821 reports with community hospitals predominating (70%). Mean patient age was 4 years (median: 0.9 years). The most common error locations were NICUs, general care units, PICUs, pediatric units, and inpatient pharmacies. Drug administration, particularly improper dosing, was implicated most commonly. Severity analysis showed 5% "near misses," 91% errors without harm, and 4% harmful errors, with no reported fatalities. A total of 893 medications were cited in 821 reports. Diuretics were cited most frequently, followed by antihypertensives, angiotensin inhibitors, β-adrenergic receptor blockers, digoxin, and calcium channel blockers. Calcium channel blockers, phosphodiesterase inhibitors, antiarrhythmics, and digoxin had the largest proportions of harmful events, although the values were not statistically significantly different from those for other drug classes. Infants <1 year of age accounted for 50% of reports. Proportions of harmful events did not differ according to age.

It turned out that most of the errors found by these researchers were due to improper dosing during administration of a cardiovascular medication.  Hopefully, as hospitals continue to improve their drug-delivery systems, this type of medical error will become less and less frequent in the future.

If this topic interests you, perhaps you want to take a look at our collection of past articles concerning various aspects of medication errors.

July 2009 Medical Journal Article Suggests That Zelnorm May Not Cause Heart Attacks And Strokes

FDA And Health Canada Had Zelnorm Removed From Respective Markets In March 2007 Due To Concerns About Cardiovascular Safety

(Posted by Tom Lamb at DrugInjuryWatch.com)

In November 2008 a national class action was filed against Novartis Pharmaceuticals Canada Inc., seeking damages on behalf of all Canadians who ingested the medication Zelnorm (tegaserod) which was used by patients who had severe constipation or irritable bowel syndrome (IBS).

From a November 3, 2008 press release issued by one of the law firms that filed this Zelnorm class action lawsuit in Canada:

Zelnorm was used for the symptomatic treatment of irritable bowel syndrome (IBS) and was marketed in Canada between March, 2002 and March, 2007 when sales were suspended at the request of Health Canada. The basis for this request was stated by the defendant to be the results of a retrospective analysis of pooled clinical data that reflected a significant increased incidence of cardiovascular events in persons taking Zelnorm.

A November 5, 2008 newspaper article, "Zelnorm: Woman blames drug company for contributing to heart attack", tells us about the proposed representative plaintiff in the Canadian Zelnorm class action, Trudy Metzger of Elmira, Ontario. In November of 2006, Mrs. Metzger was a healthy and active mother of five when, two days before her 37th birthday, she suffered a severe heart attack. According to this news report, Mrs. Metzger had been taking Zelnorm for about five months prior to her heart attack.

Almost nine months later, however, a new medical journal article suggests that Zelnorm might not cause an increased risk of heart attacks like the one Mrs. Metzger suffered.

The July 15, 2009 edition of the Journal of Cardiovascular Pharmacology and Therapeutics there is a report, "Lack of Association of Tegaserod With Adverse Cardiovascular Outcomes in a Matched Case-Control Study.", that reassesses the cardiovascular safety of Zelnorm (tegaserod).

From the Abstract for this July 2009 medical journal article:

In March 2007, the US Food and Drug Administration (FDA) suspended its use citing increased cardiovascular (CV) events in clinical trials. However, there is no known mechanistic basis for an adverse CV effect. To reassess the CV safety of tegaserod, teagaserod-treated patients (pts) in the Intermountain Healthcare database were identified (n = 2603), matched 1:6 with untreated (n = 15,618) patients by age, sex, and date of tegaserod initiation, and followed for an average of 2.5 years....  This large epidemiologic study failed to confirm a reported large event differential for tegaserod that was noted incidentally in a clinical trials database, suggesting that the prior observation may have been due to chance.

For more about this March 2007 Zelnorm recall in the U.S., see my earlier article: "Constipation Medication Zelnorm Linked To Apparent Increased Risk Of Heart Attacks And Strokes".

We will continue to watch for medical journal articles about safety studies concerning Zelnorm and monitor the progress of Zelnorm lawsuits filed on behalf of patients who suffered a heart attack or stroke while using Zelnorm.

An Overview Of Drug-Induced Liver Failure And Some Ideas On How To Improve The Situation

July 2009 Liver Transplantation Article Reports The Findings And Accompanying Editorial Makes The Recommendations

(Posted by Tom Lamb at DrugInjuryWatch.com)

In its July 2009 edition the medical journal Liver Transplantation published an article that provides an overview of the current situation concerning drug-induced acute liver failure (DIALF) in the U.S. and an editorial that makes some recommendations about how we might improve that situation going forward.

The article is "Outcome of liver transplantation for drug-induced acute liver failure in the United States: Analysis of the united network for organ sharing database", and from its Abstract we learn what the researchers investigated for their article:

Acute liver failure (ALF) is an uncommon but potentially lethal drug-related adverse effect that often leads to liver transplantation (LT) or death. A retrospective cohort study was performed with the United Network for Organ Sharing Standard Transplant Analysis and Research files. Recipients who underwent LT for drug-induced acute liver failure (DIALF) from 1987 through 2006 were analyzed. A total of 661 patients transplanted for DIALF were included in the analysis.

These researchers found that the four drug groups most often responsible for liver transplant due to drug-induced liver failure were acetaminophen (40%), antituberculosis drugs (8%), antiepileptics (7%), and antibiotics (6%).

Further, they point out in their article that acute liver failure (ALF) is "the leading cause of regulatory action, including withdrawal of drugs from the market, restrictions in indications, and warnings to healthcare providers and patients, in the United States over the past 5 decades."

Moving on to the editorial, which had no Abstract, we rely upon a piece from the Medscape Medical News entitled "Drug-Induced Acute Liver Failure Very Rare, But Can Be Fatal" (free registration required):

In an accompanying editorial, Paul H. Hayashi, from the University of North Carolina at Chapel Hill, and Paul B. Watkins, from the Institute for Drug Safety at the Hamner Institutes of Health Sciences, Research Triangle Park, North Carolina, recommend more focused research on drug- induced liver injury in pediatric populations. They also note that the clinical usefulness of the predictive model, if validated, may be limited.

"Large registries such as the UNOS [United Network for Organ Sharing] database provide valuable population-based data to form hypotheses, but they lack all desired phenotypic information about the patients," the editorialists conclude. "Multicenter studies such as the Acute Liver Failure Study Group and Drug Induced Liver Injury Network can provide detailed individual patient data, sera, and genomic DNA, which can be used to investigate these new hypotheses. The combined efforts will hopefully shed better light on preventive factors, including genetic predisposition, and move us beyond simply reporting cases and case series."

While drug-induced liver failure is, fortunately, a rare occurrence in the U.S. it can be fatal and, therefore, is a serious public health issue deserving of more attention.

History Of Singulair And Psychiatric Adverse Reactions In Canada: 1997 - January 2009

July 2009 Canadian Adverse Reaction Newsletter Provides Summary Of Reports Made To Health Canada

(Posted by Tom Lamb at DrugInjuryWatch.com)

Singulair (montelukast) has been marketed in Canada since 1997.  In Canada Singulair is indicated for: (1) the prophylaxis and chronic treatment of asthma in patients 2 years of age or older; and, (2) the relief of symptoms of seasonal allergic rhinitis in patients 15 years of age and older when other treatments are not effective or not tolerated.

In the July 2009 edition of The Canadian Adverse Reaction Newsletter (CARN) there appears an article, "Montelukast (Singulair): suicidality and other psychiatric adverse reactions", which provides a summary of reports made to Health Canada from 1997 through January 31, 2009.

From this July 2009 CARN article:

From the date of marketing to Jan. 31, 2009, Health Canada received 13 adverse reaction (AR) reports related to suicidality or self-injury suspected of being associated with the use of [Singulair (montelukast)]. Eight reports stated that the reaction abated after the dose was reduced or the drug was stopped. The reaction reappeared after the reintroduction of [Singulair] in 1 case. All but 1 of the reports were received by Health Canada after the FDA's early communication [in March 2008].

From the date of marketing to Jan. 31, 2009, Health Canada received 29 other AR reports relating to depression, hostility or psychosis suspected of being associated with the use of [Singulair (montelukast)]. In 19 cases, the reaction abated after [Singulair] was stopped or the dose was reduced. The reaction reappeared after the reintroduction of [Singulair] in 4 cases. Thirteen of the 29 reports were received by Health Canada after the FDA's early communication [in March 2008].

No deaths were reported in any of the cases discussed above. Twenty-six of the 42 reports involved patients under 18 years of age (age was not indicated in 5 reports).

In the U.S. the FDA announced in June 2009 that it was requiring a new warning about an increased risk of neuropsychiatric events for Singulair.

This FDA announcement about Singulair was followed closely by a medical journal article, "Montelukast and psychiatric disorders in children.", which was published in the June 23, 2009 edition of Pharmacoepidemiology and Drug Safety.  The Abstract for this article starts:  "A signal has been raised concerning [Singulair (montelukast)] and adverse drug reactions (ADRs) in children."

We will continue to monitor and report about neuropsychiatric events in adults and children using this popular asthma drug Singulair, from Merck & Co.

Popular Asthma Medicine Singulair Associated With Psychiatric Disorders In Children

New Medical Journal Article Follows June 2009 FDA-Required Warning For Singulair About Neuropsychiatric Events

(Posted by Tom Lamb at DrugInjuryWatch.com)

On June 12, 2009 the FDA announced a new warning about an increased risk of neuropsychiatric events for the asthma medicine Singulair (montelukast)-- as well as some other less popular leukotriene inhibitors, Accolate (zafirlukast) as well as Zyflo and Zyflo CR (zileuton).

This announcement was followed closely by a medical journal article, "Montelukast and psychiatric disorders in children.", which was published in the June 23, 2009 edition of Pharmacoepidemiology and Drug Safety.  The Abstract for this new Singulair article starts with a relatively ominous line:  "A signal has been raised concerning montelukast and adverse drug reactions (ADRs) in children."

This June 2009 Singulair medical journal article presents the findings of a study whose purpose was "to evaluate psychiatric ADRs during treatment with [Singulair (montelukast)] in children."  For this purpose, a team of researchers from Department of Clinical Pharmacology and Regional Pharmacovigilance Centre, Sahlgrenska University Hospital, Göteborg, Sweden, analyzed all reports of psychiatric disorders during treatment with Singulair in children under age 18 in the Swedish ADR database SWEDIS for the period 1998 to 2007.

From the Abstract for this Swedish Singulair study concerning adverse reactions in children:

RESULTS: A total of 48 reports of psychiatric disorders in children during treatment with montelukast were found in SWEDIS. Reports appeared every year after registration. Psychiatric disorders reported more than once included nightmares (n = 15), unspecified anxiety (n = 11), aggressiveness (n = 11), sleep disorders (n = 10), insomnia (n = 3), irritability (n = 3), hallucination (n = 3), hyperactivity (n = 3), and personality disorder (n = 2). In 23 reports (48%), the child experiencing psychiatric ADRs was ADR was indicated in 35 reports. In 28 of these (80%), the time from exposure to ADR was less than 1 week. A statistical signal for psychiatric disorders appeared in the fourth quarter of 1998 (three reports, IC-value: 2.34, 95% lower confidence limit: 0.62).

These findings led the researchers to conclude that psychiatric adverse reactions can occur in children during their treatment with Singulair (montelukast), which indicated to them that "[f]urther studies are needed to establish the magnitude of the problem."

We agree that more research should be done, and soon, about the extent of Singulair possibly causing psychiatric disorders in children using this very popular asthma drug from Merck.

Smoking Cessation Drugs Chantix, Wellbutrin, And Zyban Are Getting New "Black-Box" Warning

Will Warn About Risk Of Serious Neuropsychiatric Symptoms Including Agitation, Depression, Suicidal Thoughts, And Attempted Suicide

(Posted by Tom Lamb at DrugInjuryWatch.com)

On July 1, 2009 the FDA issued a Public Health Advisory about Chantix (varenicline) as well as Wellbutrin (bupropion) and Zyban (bupropion) which announced that these smoking cessation drugs will be getting a so-called "black-box" warning:

...highlighting the risk of serious neuropsychiatric symptoms in patients using these products. These symptoms include changes in behavior, hostility, agitation, depressed mood, suicidal thoughts and behavior, and attempted suicide. The added warnings are based on the continued review of postmarketing adverse event reports for varenicline and bupropion received by the FDA. These reports included those with a temporal relationship between the use of varenicline or bupropion and suicidal events and the occurrence of suicidal ideation and suicidal behavior in patients with no history of psychiatric disease.

Contemporaneous with this July 1 FDA Public Health Advisory the FDA issued a news release -- "FDA: Boxed Warning on Serious Mental Health Events to be Required for Chantix and Zyban" -- and a document intended primarily for relevant medical professionals -- "Information for Healthcare Professionals: Varenicline (marketed as Chantix) and Bupropion (marketed as Zyban, Wellbutrin, and generics)".

This second item had some concise and helpful background information about the history of safety issues concerning Chantix, Wellbutrin, and Zyban:

FDA first informed the public about the possibility of serious neuropsychiatric symptoms with [Chantix] in the November 20, 2007 FDA Early Communication About an Ongoing Safety Review.  A complete history of related communications on [Chantix] and [Wellbutrin / Zyban] can be found at: Varenicline (marketed as Chantix) Information.  Since that time, information about serious neuropsychiatric symptoms in patients taking varenicline has been added to the POST-MARKETING EXPERIENCE section of the prescribing information.

As FDA received additional information the suggestion of a possible association between both varenicline and bupropion (which was evaluated as a comparator to varenicline) and serious neuropsychiatric symptoms, in both patients with and those without previous history of psychiatric illness, became more evident as its review progressed....

We will watch for corporate press releases from Pfizer (which sells Chantix) as well as GlaxoSmithKline (which sells Wellbutrin and Zyban) which might be issued to present the drug company's reaction to this FDA announcement about adding a black-box warning for neuropsychiatric side effects being added to their respective product's Package Insert, or label.