Drug Injury Watch

European Union's Drug Regulator Requests Stronger Warnings On Antibiotic Ketek

EMEA Action Follows Reports of Ketek-related Liver Problems In U.S.

The European Medicines Agency (EMEA) said in a January 27, 2006 statement that it had asked Sanofi-Aventis to include stronger warnings on Ketek about potential liver problems.  In more detail, the EMEA statement includes the following points:

• "This is a precautionary measure, pending the outcome of a full benefit/risk assessment of the product in the context of the ongoing renewal procedure for the marketing authorisation."
• "Cases of serious acute hepatitis, including liver failure, some of which were fatal, have been reported to and assessed by the EMEA in the context of the continuous monitoring of the safety of Ketek."
• "The reported serious liver reactions started during or immediately after treatment with Ketek and were, in most cases, reversible after use of this product was discontinued."

According to a January 27, 2006 Reuters report about the EMEA action on Ketek, a Sanofi-Aventis spokesman said, "The company takes safety matters very seriously and these events do not change the safety profile of Ketek."

This action by the European Union's drug regulatory body follows reports in the U.S. about three patients in North Carolina who developed severe liver damage after being treated with Ketek.  Those cases were reported in an article to be published in the March 21, 2006 edition of the Annals of Internal Medicine (on January 20, 2006 an "early" release version was made available online).

As for action in the U.S., the FDA has only asked doctors to monitor patients taking Ketek for symptoms of liver problems, and to immediately discontinue treatment if such symptoms developed.

(Posted by: Tom Lamb)

Hospitals Urged By JCAHO To Take Steps To Avoid Drug Errors

Medication Mistakes Kill More Than 7,000 Hospitalized Patients Each Year In U.S.

On January 25, 2006 the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) issued an alert urging hospitals to take several steps intended to avoid drug errors that often occur when patients are transferred or discharged.

According to this JCAHO safety alert, in 2005 there were more than 2,000 cases of drug errors or medication mistakes were submitted to a voluntary medication error reporting program for health care providers maintained by U.S. Pharmacopeia.  Due to the generally acknowledged "under-reporting" of the medication mistakes, however, it has been estimated that drug errors kill more than 7,000 hospitalized patients nationwide each year.

The JCAHO report stated that most of medication mistakes involving hospitalized patients -- such as getting double doses causing an adverse reaction or incompatible drugs resulting in a drug-drug interaction -- are due to inadequate record-keeping.

According to this 2006 JCAHO safety alert -- entitled "Sentinel Event Alert Issue 35: Using medication reconciliation to prevent errors" -- hospitals can help avoid these types of medication errors by:

• listing medications and proper doses in a "highly visible" place on patient charts;
• communicating that information to doctors, nurses, and patients during transfers; and,
• making sure patients have accurate lists of medication and instructions for use when discharged.

One hopes that all of the 15,000 hospitals and health care organizations which received this January 2006 JCAHO alert about medication errors will take action to implement these simple but very significant steps.

(Posted by: Tom Lamb)

Three Vioxx Trial Dates In Early 2006 For Federal Court MDL

February, March, And April 2006: Vioxx Trials In New Orleans Before Judge Fallon

As has been known since early December 2005, a re-trial of the Irvin / Plunkett v. Merck lawsuit will start on February 6, 2006 with Judge Eldon Fallon presiding.  This trial will take place in New Orleans, home of the federal court Vioxx MDL litigation.  The initial trial of the Irvin / Plunkett Vioxx case, which ended in a mistrial, was held in Houston due to circumstances related to Hurricane Katrina.

In mid-January 2006, it was announced that Judge Fallon has scheduled two more Vioxx cases for trial, one starting on March 13, 2006, and a second case to start sometime in April 2006.  Both of these Vioxx trials will be in New Orleans, also.

Each of these first three Vioxx federal court trials involve different Vioxx-use periods.  Richard Irvin used Vioxx for only a short term prior to his death.  Ellis Diaz, the plaintiff in the March 2006 Vioxx trial in New Orleans, is considered to be a medium-term user of Vioxx.  And the April 2006 case involves Charles Borowicz and long-term use of Vioxx -- presumably more than 18 months -- according to news reports published in January 2006.

Period of Vioxx use is a critical issue in the Vioxx litigation because Merck & Co. withdrew Vioxx from the market in September 2004 when a study showed that Vioxx could double one's risk of having a heart attack or a stroke if taken for 18 months or longer.  Since the Vioxx recall, Merck and its lawyers have maintained that there are no cardiovascular risks for people with periods of Vioxx use less than 18 months.

Despite this "implied" concession that 18 months of Vioxx use might cause a heart attack or a stroke, however, Merck has consistently asserted that it will defend itself against each Vioxx lawsuit (apparently regardless of the Vioxx-use period), and settle none.

(Posted by: Tom Lamb)

Reports Of Liver Problems Associated With Antibiotic Ketek

Three NC Hospital Cases Subject Of Article In Annals Of Internal Medicine

On January 20, 2006 the Annals of Internal Medicine published online an "early" release version of an article describing liver problems associated with the antibiotic Ketek (telithromycin).  The print version of this article will be found in the March 21, 2006 edition of the medical journal.

In the three cases described in the Annals of Internal Medicine article, patients at Carolinas Medical Center, in Charlotte, North Carolina, developed differing degrees of liver problems after taking Ketek.  One patient died from liver failure two weeks after taking Ketek for five days, another patient required a liver transplant after using Ketek, and a third person developed drug-induced hepatitis after Ketek therapy but later recovered.  The authors of the article point out, however, that these three cases do not prove that Ketek caused the liver problems.

In connection with the early release of the Annals of Internal Medicine article about the three North Carolina cases involving liver problems after Ketek use, the FDA issued a MedWatch Alert concerning Ketek and possible liver problems.

The antibiotic Ketek is manufactured by Sanofi-Aventis SA, and was approved for the U.S. market by the FDA in April 2004 to treat acute bacterial bronchitis, sinusitis, and pneumonia.  Ketek is part of a group of medications known as macrolides that includes erythromycin, Pfizer Inc.'s Zithromax, and Abbott Laboratories' Biaxin.  To date, there have been rare reports of liver problems associated with the use of Ketek and these similar antibiotics.

As quoted in a January 20, 2006 Wall Street Journal article, John S. Hanson, one of the article's authors, tried to put the possible Ketek and liver problem "link" in perspective by stating:

"These cases could represent an unusual clustering of a rare, idiosyncratic drug reaction at one medical center....  However, the severity of liver injury in two of our patients warrants this report in the medical literature and will alert other physicians to this possible link with [Ketek]."

Meanwhile, Reuters reported on January 21, 2006 that Sanofi-Aventis says Ketek's "safety profile" remains unchanged from their perspective.

(Posted by: Tom Lamb)

Elidel And Protopic Will Finally Get Black-box Warnings

FDA: Eczema Products Must Warn About Increased Cancer Risks

On January 19, 2006 the FDA announced that two eczema products, Elidel and Protopic, must have a "black-box" warning placed on their package insert, or label, warning that these skin medications have a potential increased cancer risk and that their long-term safety has not been established. 

Eczema, or atopic dermatitis, is a chronic condition that causes dry, scaly patches on the skin that itch and can bleed.  According to the FDA, eczema affects 10% to 15% of the child-age population, making it one of the most common skin disorders seen in infants and children.

Elidel and Protopic are prescription medications, or ointments, that are applied to the skin areas with symptoms of eczema.  According to the FDA, essentially Elidel and Protopic treat eczema by suppressing the body's immune system. Some animal studies have suggested that this immunosuppression which results from dermal exposure to Elidel and Protopic causes an increased risk of cancer.

An article published by Reuters on January 19, 2006 reported about why the FDA finally (see below) decided to order the black-box warning for Elidel and Protopic:

"Food and Drug Administration officials said while a clear link between the drugs and cancer risk had not been found, there have been enough cancer reports to warrant the change. A total of 78 cases were reported for both products as of October 2005, they said.

" 'The concern that is being highlighted today is that the long-term safety of these products has not been established,' Dr. Julie Beitz, an acting office director within the FDA's office of drug evaluation, said."

Remarkably, this FDA action comes almost a full year after an FDA advisory panel, in February 2005, recommended to the agency that Elidel and Protopic have a black-box warning added to their respective labels. In March 2005 the FDA issued a statement to the effect that it agreed with the advisory panel's recommendation, and that it would require these prescription skin ointments to carry a black-box warning.

However, in the ten months leading up to the January 2006 FDA announcement, Novartis AG, the maker of Elidel, and Astellas Pharma Inc., the maker of Protopic, were successful in delaying the placement of any black-box warning on their skin cream medications.

This situation was characterized by a January 20, 2006 article in The Wall Street Journal in this manner:  "Since [March 2005], the companies and the FDA have been haggling over the final wording."

No wonder there is widespread doubt about who is in control of drug safety in the U.S. -- the FDA, or Big Pharma.

(Posted by: Tom Lamb)

Cialis Or Viagra Use After Heart Attack May Increase Blindness Risk

Study To Be Published In February Edition of British Journal of Ophthalmology

In mid-January 2006 the British Journal of Ophthalmology issued a statement previewing an American study that suggests there is a link between impotence, or erectile dysfunction (ED), drugs and blindness, specifically non-arteritic anterior ischaemic optic neuropathy (NAION).  The results of this study, conducted by scientists at the University of Alabama in Birmingham (UAB), will be published in the February 2006 edition of the medical journal.

In particular, this study focused on the ED drugs Viagra, made by Pfizer Inc., and Cialis, made by Eli Lilly & Co.  According to the preview statement issued by the British Journal of Ophthalmology (BJO), the UAB scientists investigated a small sample of 76 men who had attended one eye specialist clinic in the U.S.  All of the men had histories of heart attack or high blood pressure, and were similar in terms of age, race, and lifestyle.  According to the BJO statement, the scientists found among this group those men who had taken Pfizer's Viagra or Eli Lilly's Cialis and had had a heart attack were ten times more likely to develop NAION than men with heart attacks who had not taken either of the ED drugs.  NAION can cause permanent loss of vision in one or both eyes.

According to the BJO statement, Dr. Gerald McGwin, the lead scientist in the UAB study, states in the soon-to-be-published report:

"For patients with a history of myocardial infarction (heart attack), we did observe a strong and statistically significant association suggestive of a link between the use of Viagra and/or Cialis and an increased risk of NAION."

A January 17, 2006 article in The Wall Street Journal (WSJ) about the UAB study and BJO statement included this retort by Eli Lilly:

"Aside from the small sample size of the study, it's important to note that there are several other limitations to the authors' findings.

"Some of these include patient recall of medical history and details, the study's retrospective and observational nature, potential interviewer bias and the study population was pulled from a database of only patients who had been treated for eye-related disorders."

According to the same WSJ article, no Pfizer spokespeople were available to comment.

As background, in May 2005 the FDA announced that the agency had received more than 40 reports of non-arteritic anterior ischaemic optic neuropathy, or NAION, involving impotence drugs, but it had not determined at that time whether the impotence drugs were responsible for those blindness incidents.  Two facts have complicated the ED drug-blindness issue analysis for the FDA, and all interested parties.  The first is that NAION is the most common cause of acute optic nerve disease in people over 50 years old. The second is that most patients who take the impotence drugs have other medical risk factors which make them potentially susceptible to NAION.

Some products liability lawsuits have been filed in the U.S. on behalf of patients who have developed NAION after taking an ED drug.

(Posted by: Tom Lamb)

The Politics Of Tort Reform Bogs Down FDA's Regulatory Action

New Drug-labeling Rule Bears The Load Of Bush Appointees' Ideology

According to a January 14, 2006 article in The Wall Street Journal (WSJ), the FDA "is preparing to declare that federally approved medication labels pre-empt state law".  Essentially, these legal claim preemption provisions would serve to protect pharmaceutical companies from personal injury and wrongful death lawsuits involving their prescription drugs.  As pointed out by WSJ staff reporter Anna Wilde Mathews, this new policy barring state liability claims "would mesh with the White House's focus on tort reform."

It seems this new FDA policy will be included in the preamble of an important new drug-labeling rule, the primary purpose of which is not tort reform but, rather, to improve the format of the so-called "package insert", or label, for prescription drugs.  Ms. Mathew's WSJ article states that FDA career officials are upset with the Bush Administration appointees at the agency who are responsible for inclusion of the preemption provisions in the drug-labeling rule because those provisions "may draw controversy to an important regulatory improvement [i.e., better drug labels] that isn't itself politically divisive".  Apparently the degree of disagreement between these factions at the FDA has delayed the release of this important new rule.

This type of tort reform is not unprecedented for the Bush Administration FDA.  In recent years the FDA has filed numerous legal briefs in drug injury lawsuits asserting that such cases against drug companies should not be allowed because the federal agency's guidelines should preempt state law.

Significantly, some federal court judges have rejected that line of reasoning.  For example, in rejecting an FDA-supported request by the drug company Pfizer to bar a lawsuit concerning its antidepressant Zoloft, a federal judge wrote that "federal labeling laws are minimum standards; they do not necessarily shield manufacturers from state law liability.... state-law protections reinforce and enhance" federal efforts to protect the public.

Moreover, the inclusion of these federal preemption provisions in an FDA regulation that is suppose to be about drug-labeling reform -- not tort reform -- draws attention to the issue of, in Ms. Mathews' words, "the growing clash over the proper bounds of state and federal regulatory authority".  On this aspect, from her WSJ article:

"Yesterday, the National Conference of State Legislatures protested the move in a letter to Health and Human Services Secretary Michael Leavitt, calling it a 'thinly-veiled attempt on the part of FDA to confer upon itself authority it does not have by statute' and an 'abuse of agency process'."

Hopefully, with more attention directed to this blatant political action by the Bush Administration FDA, the federal preemption provisions will be removed from the much needed drug-labeling reform regulation.

(Posted by: Tom Lamb)

FDA Wants New Safety Studies For Adderall, Other ADHD Drugs

Reports Of Serious Adverse Events Involving Sudden Death, Heart Attack, and Stroke

Reports of sudden deaths, heart attacks, and strokes in both children and adults taking drugs to treat attention deficit hyperactivity disorder (ADHD) that have been made over time to the FDA has prompted the agency to look anew into the safety of Shire Pharmaceutical's Adderall XR and other ADHD drugs.

Cardiovascular events associated with Adderall and other ADHD drugs will be discussed at meetings of the FDA’s Drug Safety & Risk Management Advisory Committee on February 9 and February 10, 2006 in Gaithersburg, Maryland.  Specifically, the FDA wants members on this advisory committee to discuss the development of new studies aimed at determining “whether ADHD products increase the risk of adverse cardiovascular outcomes.”

In an announcement for the February 2006 advisory committee meeting, the FDA said:

• “Cases of sudden death and serious adverse events including hypertension, myocardial infarction, and stroke have been reported to the agency in association with therapeutic doses of drugs used to treat attention deficit hyperactivity disorder (ADHD) in both pediatric and adult populations."
• “The few controlled clinical studies of longer-term drug treatment of ADHD provided little information on cardiovascular risks."

In February 2005, Health Canada suspended the marketing of Shire’s Adderall XR due to reports of sudden death, heart attacks, and strokes in pediatric and adult patients.  Six months later, however, Health Canada reintroduced Adderall to the Canadian market in August 2005 not because the agency found Adderall to be safe but, rather, because "an independent panel found it impossible to accurately ascertain whether the drug increases the risk of cardiac death."

According to reporter Andrew Bridges, in a January 4, 2006 Associated Press article, Dr. Peter Gross, the chairman for this advisory committee, made this noteworthy comment on the paucity of longer-term safety studies for Adderall and other ADHD drugs: "It almost sounds like cox-2 inhibitor redux" -- alluding to the 2004 recall of Vioxx following the "delayed" discovery that Vioxx significantly increased one's risk of having a heart attack or stroke.

Dr. Gross's observation makes one wonder whether Adderall XR, essentially an extended release amphetamine, might be prove to be our next Vioxx-debacle.

(Posted by: Tom Lamb)

January 2006 FDA "Patient Safety News" Videos For Doctors Online

Edition Covers Ortho Evra, Cymbalta, Asthma Medications and More

The FDA's Patient Safety News (PSN) is a series of monthly video news shows intended primarily for doctors and other health care professionals.  Generally, this series covers significant approvals, recalls, and safety alerts for prescription drugs and medical devices.  Some of the FDA PSN videos contain footage and demonstrations relevant to protecting patients from serious side effects and other unwanted consequences.

Subjects covered in the January 2006 edition of the FDA Patient Safety News include the following:

Advisory on Long-Acting Bronchodilators

Alert on Certain Abbott Diabetes Care Blood Glucose Meters

Caution of Liver Damage and Cymbalta

Novartis Ophthalmics Recalls Certain GenTeal Products

Higher Estrogen Exposure with Ortho Evra Contraceptive Patch

New Risk of Interference with Wireless Medical Telemetry Systems

What to Do about False-Positive Troponin Test Results

Warning on Patient Observation and Monitoring for Erbitux

Certain Omron Thermometers Recalled

One can find more information about this January 2006 PSN edition and the series in general on the PSN section of the FDA's web site.   

(Posted by: Tom Lamb)

The Negative Affects of Clinical Trials Funded By Drug Companies

How Did We Get Into This Situation, And How Can We Get Out: Two Recent Editorials

In December 2005 The New England Journal of Medicine (NEJM) announced that it had learned about "inaccuracies and deletions" in data contained in an article that it had published back in 2000 about the results of the VIGOR (Vioxx Gastrointestinal Outcomes Research) study by Bombardier et. al.  In turn, later that same month, the NEJM published an "Expression of Concern" piece drawing attention to this disturbing discovery.  That item concluded by asking the authors of the 2000 VIGOR article to "submit a correction" concerning the three myocardial infarctions, or heart attacks, in the Vioxx-user group arm of that clinical study which had been omitted from their original article.  The VIGOR study was funded by Merck & Co., the manufacturer of Vioxx.

Two recent editorials have commented on the VIGOR / Vioxx study NEJM article controversy and other problems caused by clinical trials funded by drug companies.

On January 7, 2006 the Los Angeles Times published an editorial by John Abramson, the author of "Overdosed America", who is a clinical instructor at Harvard Medical School.  Dr. Abramson's editorial is titled "Drug profits infect medical studies".  In addition to referencing the Vioxx controversy, Dr. Abramson mentions how Scios, a Johnson & Johnson subsidiary, failed to include the deaths of two patients in a clinical study of Natrecor, its heart failure drug, in an article published in the Journal of Emergency Medicine.  This editorial examines how we got into these situations:

"... over the last 25 years, clinical research has been largely privatized. Three-quarters of the clinical studies published in the three most respected medical journals (the New England Journal of Medicine, the Journal of the American Medical Assn. and the Lancet) are now commercially funded. As a result, our medical knowledge grows not in the direction that best improves our health but toward corporate profits, the way that plants grow toward sunlight.

This wasn't always so. Before 1980, most medical studies were publicly funded, and most academic researchers scorned industry support. Now, however, the vast majority of clinical trials are commercially funded, and with the financial stakes so high, there is mounting evidence of individual scientists and corporations manipulating their findings."

Earlier, on December 13, 2005, the Chicago Tribune published an editorial by Merrill Goozner, the author of "The $800 Million Pill," who directs the Integrity in Science project at the Center for Science in the Public Interest. Entitled "Trial and error: With some drug researchers hiding crucial data in clinical trials, there is a way to get better science on drug safety", the Goozner editorial provides a suggested remedy to our current predicament:

"The way to get better science in front of regulators and physicians (who rely on the medical literature) is to have an independent body take control of FDA registration trials. The drug and medical device industries already pay user fees to the FDA to hasten reviews of their new product applications. The user fee law is up for renewal next year. Why not expand those fees to include paying the government to conduct the final product registration trials?

It could be done through a new institute in the National Institutes of Health, which could contract with investigators at universities, independent research institutes, or the private firms that have sprung up in recent years to conduct clinical trials...."

Without a doubt, both of these editorials are worth a full reading by anyone truly concerned with the issue of drug safety.

(Posted by: Tom Lamb)