Levaquin (also known as levofloxacin) is a popular antibiotic that has been used for years for the treatment of upper respiratory infections, urinary tract infections, prostatitis, and bacterial infections.  It is part of a class of drugs known as fluoroquinolones, which were first marketed in the United States in 1997.  The fluoroquinolone class of drugs also includes the widely-prescribed antibiotics Cipro, Floxin, and Noroxin.  There have also been some notable fluoroquinolones that have been withdrawn from the market due to safety concerns, including Trovan (liver failure); Omniflox (low blood sugar; kidney failure, and anemia); Raxar and Zagam (prolonged QT syndrome); and Tequin (severe blood sugar reactions).

For several years, there have been rising concerns about adverse events associated with use of fluoroquniolones, especially Levaquin.  According to documents filed in the Levaquin litigation, being coordinated in the United States District Court in Minnesota, the Japanese company (Daiichi Pharmaceutical Co. Ltd.) that developed both Levaquin and Floxin knew prior to approval of Levaquin for sales in the United Sates that the drug was likely to cause Achilles tendon ruptures . This risk was well documented in the early years after introduction as it was marketed throughout Europe and began to cause harm to patients.

The warning label for Levaquin has included mention of the possibility of tendon ruptures in the past, but such labels were obscure and never adequately warned patients or prescribing physicians of the magnitude of the risk or the fact that Levaquin was more toxic than other, similarly effective drugs.  Other than placing a warning in December of 2001, based on postmarketing surveillance reports in the PDR, indicating that this risk may be increased in patients receiving concomitant corticosteroids, especially in the elderly, the manufacturer did not provide any special label precautions. The manufacturer fell far short in their warnings, regarding the higher risks faced by older patients or those concomitantly taking steroids.

This is most unfortunate because deleterious effects of fluoroquinolones on tendons have been well documented since the 1980s .

Finally, in 2008, after more than 1,000 reports of serious tendon injuries and ruptures to the FDA, a Black Box warning (the highest level of warning) appeared on the label confirming that patients taking Levaquin are at greater risk for suffering a ruptured Achilles tendon.   Unfortunately, the label still fails to alert physicians and patients that Levaquin is more toxic than other similar drugs .

Levaquin is particularly risky for patients who are over the age of 60 and taking corticosteroids at the same time as Levaquin.  Studies conducted by the manufacturer  indicated that Levaquin was more toxic than Cipro; for example the study that Ortho McNeil completed in 2001, one that Johnson & Johnson completed in 2006 and another By Johnson & Johnson completed in 1993. Unfortunately, none of the studies conducted by these manufacturers were published in any noted journals . Undoubtedly, if this information were known to physicians in the Untied States, prescribers would have evaluated the risk differently and chosen one of a number of other antibiotics for treatment of their patients. As a result, doctors might have avoided subjecting their patients to the unnecessary pain and suffering associated with an Achilles tendon rupture and a host of other adverse events.

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Merck’s nightmare over Vioxx continues.  This is one that has cost the company dearly – on Wall Street, among physicians, in scientific circles, in the judicial system, and in the court of public opinion.  The latest blow came from the New England Journal of Medicine which published additional information regarding the APPROVe study, one of two studies that led to the recall of Vioxx in September of 2004.  This study included 2,586 patients who ingested Vioxx or a placebo.  After three years of use of these drugs, the study concluded that Vioxx users had a 3.6% incidence of thrombotic events (heart attacks and strokes) versus a 2% incidence in the placebo group.  The study further concluded that the increased risk of heart attacks and strokes associated with Vioxx emerged after just 18 months of use. 

As has been highly publicized, more than 50,000 patients who suffered heart attacks, strokes or died after ingesting Vioxx are now participating in a nearly $5 billion settlement program being administered through the federal court in New Orleans.  This settlement was announced after more than a year of secret negotiations and more than a dozen trials.  Just prior to announcement of the settlement, Merck faced the prospect of spending far more than $5 billion in order to continue its win-at-all-costs litigation tactics.  The Vioxx claims were submitted to a Claims Administrator over the Summer and partial payments began in August of 2008.  It is expected that all of the qualifying Vioxx claimants should have their claims reviewed and paid in full within the next 18 months.

A novel lawsuit is winding its way through the courts in St. Louis.  Thirty Missouri hospitals are pursuing claims against Altria (the parent company of Phillip Morris) and other tobacco manufacturers for the costs of medical care provided to patients with tobacco-induced diseases who were uninsured or unable to pay for their treatment.  The lawsuit has been pending for more than a decade and has had many twists and turns along the way.  Initially, the plaintiff hospitals sought more than $8 billion in damages for medical expenses incurred as far back as 1954.  The judge overseeing the case pared the claims down to include only costs incurred since 1993, which are still substantial.  It is anticipated that the case could go to trial as early as January of 2010. 

A recent study published in Kidney International, the journal of the International Society of Nephrology, noted increasing concerns over the use of gadolinium-based contrast agents in patients with renal or liver disease.  In this article, researchers from the Oregon Health and Science University urged the use of ultrasmall superparamagnetic iron oxides (USPIOs) as a safer alternative to the highly toxic gadolinium.  The scientists noted that USPIOs provided enhancement of MRI images similar to that experienced with the use of gadolinium.  This substance, which has been safely used in the past in patients with chronic kidney disease for iron supplementation therapy, was determined to be a safer alternative to the gadolinium therapies currently in use which have been repeatedly implicated as the cause of nephrogenic systemic fibrosis (NSF) in patients with pre-existing renal and liver disease. 

A September of 2008 study published in the journal Radiology, sought to further identify those patients most at risk for the development of nephrogenic systemic fibrosis (NSF) as a result of exposure to gadolinium-based contrast agents.  Nephrogenic systemic fibrosis is an incurable, devastating disease that manifests itself as significant skin thickening, widespread fibrosis, and joint contractures.  This particular disease has only one cause – contrast agents commonly used in magnetic resonance imaging (MRIs) and angiograms.

In this study, the researchers reviewed medical records for nearly 75,000 patients treated at two hospitals over a ten-year period. The study noted that standard lab measurements of renal function were helpful in identifying patients most at risk for development of NSF.  Patients with a glomerular filtration rate (eGFR) of less than 15 were at highest risk, although NSF cases were also noted in patients with eGFR scores as high as 30.  This study is consistent with others that have confirmed that a wide range of patients are at risk for development of NSF, not just those patients with advanced renal failure.  The study noted that a shocking 8.8% of patients with an eGFR of less than 15 (and not undergoing dialysis) developed NSF. The study also concluded that patients receiving the highest doses of gadolinium faced the highest risks of developing NSF .

A very dear friend once told me to be careful what you write in a letter, because it could come back to haunt you in the future.  That advice was given to me in the early 1980’s by the CEO of a company in my hometown of Reading, Pennsylvania.  We did not even have e-mail at that time, but his words certainly apply to e-mail in the year 2008.
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Unlike ink on paper, which can fade over time, e-mail can last indefinitely.  It is also important to remember that e-mails are almost too easy to write.  A person may feel very passionately about an issue one day, and decide to write and send a fiery e-mail.  However, upon further reflection, that person may regret what he or she has stated in the e-mail.  However, once e-mail has been sent, it is very hard if not impossible to un-send or to take back those words.
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So, I would urge whoever reads these words be quick to hear, slow to speak, and even slower to write e-mail.
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Patients who undergo shoulder, knee and ankle surgery often experience significant pain; particularly immediately post surgery. To try and manage that pain, physicians have often employed the use of pain pumps. These pumps inject pain killer into the body in a regulated fashion to minimize pain, while controlling the tendency toward addiction.

The pain pump is attached to a catheter, which was routinely inserted into the soft tissue near the affected joint. This use of the pump worked fine until the manufacturers of these devices started recommending that physicians could insert the catheter directly into the affected joint space and provide a much higher degree of pain relief. This was, of course, welcome news for physicians who always want to attempt to relieve or minimize the suffering of their patients. So all was good, then?

What pain pump manufacturers failed to tell physicians is that the Food & Drug Administration had never reviewed, let alone approved, the use of the pumps directly into the joint space. What the manufacturers should have known is that at least one of the manufacturer’s, McKinley Medical, asked the FDA to permit insertion of the devices into the joint space and the FDA asked for proof of efficacy. As far as we know, no data or evidence was presented to the FDA. Soon after this, Stryker Corporation purchased the exclusive rights to the pain pump from McKinley. (more…)

Caffeine, hands down, is the most popular, legal and widely abused drug on the planet.  It’s in everything including: caffeinated snacks; soft drinks; alcoholic beverages; over the counter supplements; not to mention popular face cream and products that boast a remedy for cellulite. Caffeine is legal, but even too much of a good thing can cause harm.  Perhaps the fastest growing new line of caffeine containing products is energy drinks. Blogger and author of “Nutrition for Dummies”, Carol Ann Rinzler, examined the labels of the top three energy drinks. (more…)

In the last couple of years, it seems as if there has been an increase in the recalls issued by the FDA; contact lens solutions, tainted meat, poisonous vegetables, toxic toys and poisonous pet food to name just a few. In response to concerns over the recent headlines“Infant Formula from China Tainted by Chemical”, the FDA has issued a warning that toxic baby formula “even though it is not legally approved for importation” may have made its way into local markets here in the USA.

The concerning chemical in the formula is melamine. As some of you may recall Melamine is the same chemical associated with the massive pet food recall in 2007 after thousands of U.S dogs and cats were poisoned and killed after ingesting toxic pet food. It was later determined, according to veterinary pathologists, “that the combination of melamine and cyanuric acid caused crystals to form in the urinary tracts of animals” leading to their untimely death.

As we have seen in the world of dietary supplements, manufactures and suppliers in China use the” nitrogen rich” Melamine to make the product appear to be containing more protein than it actually does to pass  the standard tests for protein ingredient  in bulk foods. The additive Melamine makes the product “appear to be gluten” and they are then sold “as gluten” to pet food manufacturers U.S. and Canadian.

Melamine causes chronic toxicity and “Ingestion of melamine may lead to reproductive damage, or bladder or kidney stones, which can lead to bladder cancer”.
Although the press release by the FDA cited that there is no “known threat” it is also not “known” as to whether or not some of the contaminated product has found it’s way into specialty stores in the USA. Although not very reassuring, they do urge  “Individuals should contact their health care professional if they have questions regarding their infant’s health or if they note changes in their infant’s health status.”

There have been many reports in the past decade over contaminated baby food and formula ranging from salmonella to this most  recent contamination threat of formula found to contain melamine, which has been cited as the culprit in China for babies developing serious kidney problems. CBC News reported that spokesman Mao Qunan stated, the agency investigators concluded the chemical (Melamine) was added when the milk was purchased from farmers but gave no other details. Quanan said, 78 “suspicious people” were summoned for questioning. Sanlu Group, the major Chinese dairy that produced the formula, has recalled 700 tons of the products, the Xinhua News Agency reported. “China Health Ministry issued a statement “Those responsible will face serious punishment.” 

There is no question that technological changes have revolutionized discovery in civil litigation, particularly in cases where the parties seek large volumes of documents from their opponents. Medical device and pharmaceutical litigation come to mind. How to manage so-called “e-discovery” is on the minds and lips of many lawyers. In theory, e-discovery techniques should provide a discovering party with powerful weapons to ferret out litigants who cheat the system by hiding the ball. Unfortunately, this is not necessarily the case. Technological sophistication in the discovery process does not, by itself, guarantee integrity in the content of a party’s discovery responses. In fact, recent experience teaches that technology can be used improperly to increase the obstacle’s that a party faces in discovering the truth. For example, document or file formatting can reduce a discovering party’s ability to efficiently search documents for critical information.

I was recently reminded, however, that it is important to return to the rules of procedure occasionally as a source of protection against unprincipled discovery practices by well-heeled litigants and resourceful lawyers. In a recent case handled by our firm, the defendant produced more than two million pages of documents relating to the development and sale of a medical device. Although the production was in an electronic format, it was marked by a high degree of disorganization. It was very difficult to manage and highly trained personnel on our staff suspected that the coding and formatting of the documents had been designed to impair their usefulness. The modern-day equivalent of shuffling a pile of papers.

Courts have the power to deal with problems that arise in the brave new world of discovery problems. Many courts, however, lack the sophistication, experience or resources to handle important e-discovery disputes and problems. That’s where the rules of procedure can come in handy. Rule 34 of the Federal Rules of Civil Procedure (and most of the analogous state rules), for example, gives a producing party a choice. One choice is to identify its documents to correspond with the discrete requests served in a request for production. The other is to produce documents as kept in the “usual course of business.” In cases where there is a large volume of records, the party making a document request has a potentially significant advantage if the producing party’s responses identify how its production corresponds to the requests.

The historical reasons that the rulemakers created this choice are clear. One reason was to prevent discovery abuses via document production in “volume or disarray.” Another was to ensure production of documents “in the order in which the documents are actually kept in the usual course of business so that there is an internal logic reflecting business use.” “Second Report of the Special Committee for the Study of Discovery Abuse,” American Bar Ass’n Section of Litigation, 92 F.R.D. 137, 177-78 (1980).

Recent experience, however, teaches that some manufacturers use the “usual course of business” option to do exactly what the rule seeks to avoid, make document production in “volume or disarray.” In the case which I mention, the defendant took the position that its document production was made in the “usual course of business.” In fact, every page of the documents produced was examined, vetted and analyzed before the production took place. The defendant represented in court that a team of thirty to forty full-time outside lawyers was working on the production on a full-time basis. Free-ranging redactions, many with obviously material content, filled the production. Hundreds of thousands of pages were withheld on grounds of privilege. While the defendant was a large, sophisticated corporation with thousands of employees, there was absolutely no “internal logic” to its production.

As our frustration in working with the defendant’s production grew, I began to reexamine the purposes of the Rule 34 option and the decisions interpreting the rule. Despite the obvious importance of this issue, there is not a great deal of authority as to what constitutes production of records as maintained in the “usual course of business.” But some things are relatively clear. When a party makes this election, that party has the burden of proving that it has in fact produced its documents in as maintained “in the usual course of business.” Cardenas v. Dorel Juvenile Group, 230 F.R.D. 611, 618-19 (D. Kan. 2005).

One of the problems we were having was that the defendant had obtained internal records from different people it called “custodians” and purported to produce those records on a custodian by custodian basis. When the records were combined and produced to us, however, there was no apparent principle relating to their organization. At least one federal judge has found that this process is not authorized by Rule 34. In Scripps Clinic & Research Foundation v. Baxter Travelol Laboratories, Inc., CIV. A. No. 87-140-CMW, 1988 Westlaw 70013 (D. Del. June 21, 1998), the court explained, “Baxter . . . failed to produce the documents as they were kept in the ordinary course of business. The documents were gathered from many people and transferred to Scripps in an unintelligible manner. This is insufficient under Rule 34(b).”

Even once these failures are identified, it is very difficult to persuade a judge to do anything about it. In the case to which I refer, however, we were able to persuade the trial court that the remedy is to require the producing party go back and redo its production, by identifying those documents (and their Bates numbers) which correspond to the discrete discovery requests. The decision in Cardenas supported the trial court’s conclusion. Our defendant complained bitterly about the trial court’s ruling, particularly about the expense and effort associated with having to redo its responses to our substantial discovery requests. The interlocutory appeal that followed was dismissed.

I learned a few things from this experience. I was reminded of the importance of narrowly tailoring discovery responses. The more specific we are in our document requests, the more likely we will be able to help get the courts to pin down our opponents in providing responsive information. I also learned that we should never accept without corroboration the representations of our adversaries that their document production is based on the “usual course of business.” We should be careful about testing those representations when the need arises, and challenging them when they unduly and improperly complicate our efforts to find the truth.