Drug Injury Watch

More Than One Million Hospitalized Patients Experienced Adverse Drug Reactions (ADRs) In 2004

Findings Of April 2007 AHRQ Report On Side Effects And Other Medication Problems In American Hospitals

(Posted by Tom Lamb at DrugInjuryWatch.com)

A recent online article provided a summary of the findings from the "Adverse Drug Events in U.S. Hospitals, 2004" report issued in April 2007 by the Agency for Healthcare Research and Quality (AHRQ).

According to this online article, entitled "Over 1 Million American Hospital Patients Experience Side Effects And Other Problems With Their Medications":

• In 2004, 1.2 million hospitalized patients experienced an adverse drug reaction (ADR);
• 90 percent of these ADRs were due to a side effect from a medication that was properly administered; and,
• Just 8.6 percent of ADRs among hospitalized patients were because they were given the wrong drug or the wrong dose in the hospital or because they accidentally took an overdose or the wrong drug before entering the hospital.

Other findings from this April 2007 AHRQ report, which is part of its Healthcare Cost and Utilization Project (HCUP), and published in its Statistical Brief #29:

• Average total hospital costs for patients who experienced drug side effects or other ADRs were $2500 more than for patients who did not experience any drug side effects or other ADRs  ($10,100 compared with $7,600);
• Corticosteroids, blood thinners, and anti-cancer drugs were the top three types of drugs involved in these hospital ADRs, and those events which involved drug side effects were mostly due to side effects from properly administered medications;
• As for those hospitalized patients who suffered side effects from properly administered drugs, they tended to be older (average age: 64 years old) than patients who suffered from side effects related to wrongly administered medication (average age: 47 years old); and,
• Nearly 60 percent of the hospitalized patients in America who experienced an ADR during 2004 were women.

Healthcare providers and patients who are interested in these findings about ADRs in American hospitals may also want to take a look at the "List of High-Alert Medications", which is put out by the Institute for Safe Medication Practices (ISMP).

According to this ISMP document:

High-alert medications are drugs that bear a heightened risk of causing significant patient harm when they are used in error.  Although mistakes may or may not be more common with these drugs, the consequences of an error with these medications are clearly more devastating to patients.

Lastly, healthcare providers and patients are encouraged to report actual as well as potential medication errors to the Medication Errors Reporting Program (MERP).  Such reports can be made online at http://www.ismp.org or by calling 1-800-FAIL-SAFE.

Former FDA Physician David Ross Criticizes Agency's Handling Of Ketek Case In April 2007 NEJM Article

FDA Staffers' Letter To Editor Defends Steps Taken Over Time As Regards This Controversial Sanofi-Aventis Antibiotic

(Posted by Tom Lamb at DrugInjuryWatch.com)

In the April 19, 2007 New England Journal of Medicine (NEJM) appears "The FDA and the Case of Ketek", by David B. Ross, M.D., Ph.D., a former FDA staff physician who was involved in the agency's review of the antibiotic Ketek (telithromycin).

In his Ketek article, Dr. David Ross goes through "several lessons to be learned from an examination of the events surrounding the approval of [Ketek]".

As can be expected in a telling of the Ketek approval story, there is considerable discussion of the infamous drug-safety study known as study 3014 and its "issues of data integrity".

The several points made by Dr. David Ross -- who is currently a clinical assistant professor at George Washington University School of Medicine and Health Sciences --  as concerns the FDA's handling of the Ketek case are captured in these two paragraphs from his April 2007 NEJM article:

The review of Ketek was thus marked by pronounced departures from accepted review practices. In addition to the use of fraudulent data, the substitution of uncontrolled postmarket safety reports for controlled clinical trial data, and the acceptance of trials that could not show efficacy, there was also overt internal pressure brought to bear on FDA reviewers to alter their conclusions....

In the face of Congressional subpoenas and unfavorable publicity, reviewers at the FDA were warned at a June 2006 meeting by Andrew von Eschenbach, then the acting FDA commissioner, not to discuss Ketek outside the agency. By this time, 23 cases of acute severe liver injury and 12 cases of acute liver failure, 4 of them fatal, had been linked to Ketek. By the end of 2006, Ketek had been implicated in 53 cases of hepatotoxic effects. The FDA did not relabel Ketek to indicate its possible severe hepatotoxicity until 16 months after the first liver-failure cases became public. The withdrawal of approval for two indications, acute bacterial sinusitis and acute exacerbation of chronic bronchitis, for which Ketek's efficacy had never been demonstrated, did not occur until February 12, 2007 — only a day before the Congressional hearing on Ketek.

The same April 19, 2007 NEJM edition has a letter to the editor seemingly intended as the FDA's response to this Dr. David Ross article about Ketek.  This FDA letter, entitled "Ketek -- The FDA Perspective", is written jointly by Janice Soreth, M.D., Edward Cox, M.D., M.P.H., Sandra Kweder, M.D., John Jenkins, M.D., and Steven Galson, M.D., M.P.H., of the FDA's Center for Drug Evaluation and Research.

As for Ketek study 3014, this April 2007 NEJM letter to the editor asserts "there was no intention to deceive the advisory committee or the public regarding our review of study 3014."  These FDA staff members conclude their letter with a recap of recent actions by the FDA and Sanofi-Aventis regarding Ketek:

The FDA monitored the safety of Ketek after approval and conducted a 1-year postapproval safety review in the spring of 2005. After three reports of serious hepatotoxicity were published in January 2006, we conducted an analysis of the available safety data that led to the addition of a bolded warning regarding hepatotoxicity in June 2006. After an advisory committee review of Ketek in December 2006, in February 2007 we added a boxed warning and Medication Guide to the label and removed two indications. Although we believe that the potential benefits of Ketek outweigh its risks when it is used according to the current approved label, we continue our safety surveillance and will take further actions if warranted.

We end, however, by going back to the last sentence of Dr. David Ross' April 2007 NEJM Ketek article:

If the case of Ketek leads to important reforms, then the drug may have done some good after all.

No doubt, we have not heard the last about the FDA's handling of this Ketek case.

Significant Increase In Deaths For Aranesp Users In Comparison To Patients Taking Placebo

Amgen-Sponsored Study Was Testing Aranesp In Cancer Patients Who Developed Anemia

(Posted by Tom Lamb at DrugInjuryWatch.com)

An April 17, 2007 Wall Street Journal (WSJ) article about the results of a new study concerning Aranesp revealed more bad news for Amgen Inc., the maker of this anemia drug:

Amgen's drug Aranesp didn't reduce the need for blood transfusions in anemic cancer patients and was linked to a nearly 45% increase in deaths compared with patients taking a placebo.

These latest safety findings, first presented on April 16, 2007 at an American Association for Cancer Research meeting in Los Angeles, came out of an Amgen-sponsored study which was examining the use of Aranesp in patients who had become anemic because of their cancer -- as opposed to developing anemia as a side effect of the chemotherapy treatments for their cancer.

More details about this Aranesp study was provided by the April 18 WSJ article:

Nearly 1,000 patients were enrolled in the study with many kinds of cancer, including breast, prostate and non-small-cell lung cancers. The patients weren't receiving chemotherapy, and most had very advanced cancer classed as stage III or IV disease. Patients were treated with Aranesp.... Treatment continued for 16 weeks or until the patient required a transfusion. People in the control group received a placebo, or inactive substance.

Earlier reports of potential risks associated with the use of Aranesp as well as Epogen and Procrit had already prompted the FDA to schedule a May 10, 2007 meeting of its Oncology Drugs Advisory Committee in order to consider the safety of these increasingly controversial erythropoiesis-stimulating agents.

Vioxx Judge Wilson In Texas Might Rule For Merck On Preemption Issue And Dismiss Ledbetter Case

WSJ Reports That Judge Wilson's Ruling In This One Vioxx Case Could Affect Other 1000 Texas Vioxx Cases

(Posted by Tom Lamb at DrugInjuryWatch.com)

Reporter Heather Won Tesoriero broke the news in an April 13, 2007 Wall Street Journal (WSJ) article about Texas Vioxx cases:

A ruling from a Texas judge coming as soon as Monday is expected to undercut the legal foundation for all 1,000 Vioxx cases brought against Merck & Co. by Texas plaintiffs, providing a potentially significant boon to Merck's defense efforts.

The judge has informed both sides in a state-court Vioxx case that he will dismiss it based on a recently finalized Food and Drug Administration rule, according to a person familiar with the matter. He then told attorneys involved in some of the other 1,000 Vioxx cases in Texas state courts that his ruling could affect the whole group.

For background, as in New Jersey and California, all Vioxx personal injury and wrongful death cases filed in the Texas state court system have been "consolidated" before one judge. In Texas, the judge overseeing the approximate 1000 Texas Vioxx cases is Harris County District Court Judge Randy Wilson.  In New Jersey, Judge Carol Higbee has control over about 14,000 Vioxx cases, and in California Judge Victoria Chaney has an estimated 4,500 Vioxx cases on her docket.

This particular legal ruling by Judge Wilson was made in the Vioxx case involving Ruby Ledbetter, who alleged that her heart attack was caused by her use of Vioxx, which she had taken for more than a year before that heart attack.

Returning to the April 13 WSJ article by Ms. Tesoriero:

• Judge Wilson said he was granting Merck's motion to dismiss Ms. Ledbetter's case, citing an FDA policy rule issued in February 2006. That rule says the agency's approval process trumps state law in how manufacturers of health-care products must warn consumers about their potential risks [in personal injury and wrongful death lawsuits like the Ledbetter Vioxx case].
• [Judge Wilson]... told the attorneys he will suspend the [other 1000 Texas Vioxx] lawsuits until the state's appeals court rules on his judgment. He said he would issue his written order as soon as next week, according to the person with knowledge of the matter.

Merck's current position on this significant development was reported in an April 13, 2007 Reuters article about the reported Texas Vioxx ruling in favor of Merck:

"We can't confirm or deny the report, but we will analyze it once we see what the Judge actually says in his decision," Kent Jarrell, a spokesman for Merck's outside counsel, told Reuters.

No doubt that the eyes of many people concerned with the Vioxx litigation will be on Texas state court Judge Randy Wilson next week.

Third California Vioxx Trial A No-Go; Plaintiff Berwick Drops Case Day Before Jury Selection Was To Start

Judge Victoria Chaney To Consider Status Of Upcoming California State Court Vioxx Trials At April 11, 2007 Hearing

(Posted by Tom Lamb at DrugInjuryWatch.com)

Plaintiff Lowell Berwick, who claimed his March 2004 heart attack at age 61 was caused by his ten-months use of Vioxx, dropped his lawsuit against Merck & Co. on April 9, 2007, the day before jury selection for his California state court trial was to start.

Los Angeles Superior Court Judge Victoria Chaney -- who is overseeing the consolidated California Vioxx litigation, Vioxx Cases, JCCP No. 4247 (California Superior Court, Los Angeles County) -- granted the motion to dismiss filed by Mr. Berwick's attorneys.

An April 9, 2007 report from a Los Angeles CBS affiliate stated that Kent Jarrell, a spokesman for the law firm representing Merck, said the plaintiff's lawyer had requested that this case be dismissed because Mr. Berwick was concerned about a possible negative affect on his health from the anticipated lengthy trial.  The report stated, also, that Mr.Berwick's lawyer was not immediately available for comment.

The Berwick case would have been the third Vioxx case to go to trial in California.

The first California Vioxx trial involved 71-year old Stewart Greenberg, who suffered a heart attack after using Vioxx; that trial ended with a verdict for Merck in August 2006.

The second Vioxx trial in California involved two plaintiffs, 56-year old Lawrence Appell and 77-year old Rudolph Arrigale, both of whom suffered heart attacks after using Vioxx; that trial ended with Judge Chaney declaring a mistrial on January 18, 2007.

According to the Los Angeles CBS report, at an April 11, 2007 hearing Judge Chaney will review and consider the status of other California state court Vioxx cases that might go to trial in 2007.

P.S.  On his blog, Legal Underground, St. Louis attorney Evan Schaeffer has posted the most recent list of federal court and state court Vioxx trial settings through October 2007, which he reports was compiled by the Plaintiffs' and Defendants' Liaison Counsel in the federal court Vioxx MDL litigation.

FDA Orchestrates Voluntary Recall of Parkinson's Disease Drug Permax

Action Follows News Of Studies Which Revealed Link To Serious Heart Valve Damage

(Posted by Tom Lamb at DrugInjuryWatch.com)

On March 29, 2007 the FDA announced that Permax as well as two generic pergolide drug products, which had been used to treat Parkinson’s disease, would be voluntarily removed from the U. S. market because Permax (pergolide) had been linked to serious heart valve damage.

From the FDA News item entitled "FDA Announces Voluntary Withdrawal of Pergolide Products":

The products being withdrawn are Permax, the trade name for pergolide marketed by Valeant Pharmaceuticals, and two generic versions of pergolide manufactured by Par and Teva. Pergolide is in a class of medications called dopamine agonists and is used with levodopa and carbidopa to manage the symptoms (tremors and slowness of movement) of Parkinson’s disease.

In 2006, an estimated 12,000 patients received prescriptions for pergolide from retail pharmacies in the United States. Patients taking pergolide should contact their doctors to discuss alternate treatments. Patients should not stop taking the medication, as stopping pergolide abruptly can be dangerous.

This move by the FDA follows two studies published in the New England Journal of Medicine (NEJM) as well as a more recent article published in the Archives of Neurology which seemed to confirm several previous studies that had associated Permax (pergolide) with an increased risk of developing regurgitation -- or backflow of blood -- of the mitral, tricuspid, and aortic valves of the heart. Generally, valvular regurgitation is a condition in which the heart valves do not close tightly which, in turn, allows blood to flow backward across the valves; common symptoms include shortness of breath, fatigue, and heart palpitations.

As one may recall, the two NEJM studies also discussed the association of another drug, Dostinex (cabergoline), with these heart valve side effects.  In a March 30, 2007 Wall Street Journal (WSJ) article, however, Dr. Robert Temple, director of the FDA's Offices of Drug Evaluation, said his agency is "not particularly worried" about Dostinex:

The two studies, published in January in the New England Journal of Medicine, also tied another Parkinson's drug, Pfizer Inc.'s Dostinex, or cabergoline, to heart-valve problems. In the U.S., FDA officials said, cabergoline is sold for a hormone condition, not for Parkinson's, and is recommended at far lower doses than the ones tied to the heart problems. Dr. Temple said the agency was "not particularly worried" about the drug.

Also from this March 30 WSJ article, it seems as if Eli Lilly & Co. disputes this FDA action concerning pergolide products, including Permax:

Eli Lilly & Co., which began marketing pergolide in the U.S. in 1989 and still sells it overseas, said it has no plans to pull it from foreign markets. The drug is "still an important treatment option for Parkinson's disease in Europe and around the globe," a spokesman for the Indianapolis company said. Eli Lilly believes "the risk-benefit profile of pergolide is still favorable" for certain patients when they follow the safety recommendations, he said.

In connection with this recall, the FDA has released a Public Health Advisory about Permax (pergolide) intended to provide information and recommendations to doctors, pharmacists, and patients in the wake of Permax being withdrawn from the market.

Constipation Medication Zelnorm Linked To Apparent Increased Risk Of Heart Attacks And Strokes

Novartis Suspends Sales After FDA Determines That Risks Of Serious Side Effects Outweigh Benefits Of Zelnorm

(Posted by Tom Lamb at DrugInjuryWatch.com)

On March 30, 2007 the FDA announced that Novartis Pharmaceuticals Corporation had suspended the marketing and sales of Zelnorm (tegaserod), a widely prescribed medication for irritable bowel syndrome (IBS) and constipation, due to an apparent increased risk of heart attacks and strokes in patients using Zelnorm.

According to a March 30, 2007 FDA News release entitled "FDA Announces Discontinued Marketing of GI Drug, Zelnorm, for Safety Reasons":

Zelnorm was approved for short-term treatment of women with irritable bowel syndrome whose primary symptom is constipation and for men and women younger than 65 with chronic constipation.

An analysis of 29 placebo-controlled clinical trials comprising over 18,000 patients conducted by Novartis found 0.1% of patients taking Zelnorm showed evidence of a serious cardiovascular event, compared with 0.01% taking a placebo. The FDA concluded that, for most patients, the benefits of Zelnorm no longer outweigh the risks. The agency is working with the manufacturer to keep the drug available for those who have no other treatment options.

A time line of the events leading up to Novartis' withdrawal of Zelnorm from the U.S. market is outlined in a March 31, 2007 New York Times article by Gardiner Harris:

The worries about Zelnorm began with a routine safety review last year by drug officials in Switzerland. To prepare, Novartis scientists gathered data from all 29 of their Zelnorm studies and looked for patterns. By January, they had found the difference in heart problems.

Thirteen cases of heart problems in more than 11,000 patients is about what one might find in a normal population, said Dr. Stephen Cunningham, head of clinical development and medical affairs in the United States at Novartis.

The company reported its finding to the drug agency on Feb. 22. The agency mobilized a team of reviewers.

The team met with Novartis officials on March 15 to ask questions. On Thursday, the F.D.A. notified the company that it had decided that Zelnorm should be withdrawn. On Friday the company complied.

Zelnorm was approved by the FDA in July 2002 for short-term treatment of women with irritable bowel syndrome whose primary symptom is constipation and approved in August 2004 for men and women younger than 65 with chronic constipation.

As for how often Zelnorm was prescribed in the U.S., according to a March 30, 2007 Reuters article:

Zelnorm was Novartis's 12th-biggest selling drug in 2006, with global turnover growing 30 percent to $561 million, of which $488 million was generated in the United States.

About 500,000 U.S. patients are taking Zelnorm, Novartis spokeswoman Anna Frable said.

The FDA has released a Public Health Advisory about Zelnorm intended to give doctors and patients further information about why Zelnorm was taken off the market.