In an unpublished opinion file on April 9, the Court of Appeals for the 5th Circuit affirmed a previous decision in one of the Reglan generics cases, Whitener v. Pliva, Inc. This ruling upholds the district court’s grant of summary judgment in favor of the defendant drug companies on the grounds that the defendants performed no off-label promotional activities.

Lindsey and Joshua Whitener’s son was born prematurely and with severe birth defects after Mrs. Whitener used metoclopramide, a generic form of the heartburn drug Reglan. Mrs. Whitener was suffering nausea and morning sickness and her doctor, Dr. John McCrossen, prescribed metoclopramide as an off-label treatment due to previous successes he’d had with the drug.

The FDA-approved label did not mention any warnings regarding used during pregnancy nor did it recommend metoclopramide as a treatment for pregnancy-related nausea. The Whiteners filed suit in 2010 alleging that the drug’s manufacturers failed to warn them of the danger of using their product during pregnancy and also that the manufacturers had engaged in a “complex scheme” of promotion of the off-label use.

Of the six defendants, three were manufacturers of brand name Reglan (Alaven Pharmaceutical L.L.C., Meda Pharmaceuticals, Inc. and Schwarz Pharma, Inc.), which Mrs. Whitener did not use. The other three (PLIVA, Inc., Barr Laboratories, Inc. and Teva Pharmaceutical Industries, Ltd.) made generic metoclopramide, which Mrs. Whitener did use.

A 2011 U.S. Supreme Court ruling in PLIVA, Inc. v. Mensing, held that state law inadequate warning claims against generic drug manufacturers were preempted, as federal law required the generic labels to be the same as the brand name labels. The 5th Circuit granted defendants’ motions for judgment on the pleadings in the matter of the inadequate warnings. However, it allowed the claim of promotion of off-label use to proceed.

Teva was released from the case due to a jurisdictional issue. The remaining defendants moved for summary judgment on the grounds that the Whiteners could not prove that the premature birth and birth defects were directly caused by any off-label promotion in which they may have engaged. The Whitener’s own doctor, Dr. McCrossen, provided the testimony the court needed to support the motion for summary judgment.

In Dr. McCrossen’s testimony, he stated unequivocally that the decision to prescribe metoclopramide was mad based on his “clinical experience” that the drug “works good to control nausea and vomiting associated with pregnancy.” He further testified that he had never spoken to a representative of the defendants regarding the drug, nor had he been given samples. To the best of his knowledge, no one in his practice had had contact with the defendants either.

Under the court’s Rule 47.5.4, this unpublished opinion is not precedent “except under the doctrine of res judicata…, etc. An unpublished opinion may be cited pursuant to Fed. R. App. P. 32.1(a).” This does not bode well for other plaintiffs with similar claims.

Sources:

Whitener v. Pliva, Inc.

Citing Unpublished Federal Appellate Opinions Issued Before 2007

On Tuesday March 3rd, the United States Food and Drug Administration required that manufacturers of testosterone supplements (or, Low-T drugs)  include warnings on packaging for the increased risk for heart attack and stroke linked to these drugs.

In years past, a great many peer-reviewed scientific studies had demonstrated that men using Low-T drugs were at dramatically higher risk for heart attack and stroke.  Finally, this work has led the FDA to require a warning label update.

Further, labels for Low-T drugs are now required to include warnings that the medication is approved only for men with specific medical ailments.  The popularity of Low-T drugs has soared in recent years, and many men never actually have testosterone levels checked before getting a prescription.  In this way, huge numbers of men use Low-T drugs to treat “symptoms” of normal aging, placing themselves at high risk for cardiac event without informed consent.

Reuters reported yesterday that “The number of men being prescribed testosterone jumped more than 75 percent, to 2.3 million, between 2009 and 2013” and “About 70 percent of these patients were between the ages of 40 and 64, the FDA said.”

Importantly, that report noted this FDA ruling about Low-T drugs “restricts companies from marketing or promoting their products for age-related low testosterone.”

Annual sales for Low-T drugs topped $2 billion last year, and AndroGel – a popular testosterone-infused gel by Abbvie and Abbott Laboratories – took in over $900 million in sales.

For more information on Low-T drugs and their link to both heart attack and stroke, click here.

Because many men used these drugs unaware of the risks associated, many Low-T lawsuits are currently being filed.  If you or a loved one used a Low-T drug and suffered an adverse cardiac event, you may be entitled to significant financial compensation.  For a free consultation, contact our team of testosterone lawyers today.  Or, find information on Low-T lawsuits here.

(855) 452-5529

justinian@dangerousdrugs.us

 

Here is the FDA Drug Safety Communication for Low-T:

“[This information is an update to the FDA Drug Safety Communication: FDA Evaluating Risk of Stroke, Heart Attack, and Death with FDA-Approved Testosterone Products issued on January 31, 2014.]

[Posted 03/03/2015]

AUDIENCE: Health Professional, Endocrinology, Urology, Family Practice, Patient

ISSUE: FDA is requiring that the manufacturers of all approved prescription testosterone products change their labeling to clarify the approved uses of these medications. FDA is also requiring these manufacturers to add information to the labeling about a possible increased risk of heart attacks and strokes in patients taking testosterone. FDA cautions that prescription testosterone products are approved only for men who have low testosterone levels caused by certain medical conditions. The benefit and safety of these medications have not been established for the treatment of low testosterone levels due to aging, even if a man’s symptoms seem related to low testosterone.

Based on the available evidence from studies and expert input from an FDA Advisory Committee meeting, FDA has concluded that there is a possible increased cardiovascular risk associated with testosterone use. These studies included aging men treated with testosterone. Some studies reported an increased risk of heart attack, stroke, or death associated with testosterone treatment, while others did not. See the Data Summary section of the FDA Drug Safety Communication for additional details.

BACKGROUND: Testosterone is FDA-approved as replacement therapy only for men who have low testosterone levels due to disorders of the testicles, pituitary gland, orbrain that cause hypogonadism. However, FDA has become aware that testosterone is being used extensively in attempts to relieve symptoms in men who have low testosterone for no apparent reason other than aging. The benefits and safety of this use have not been established.

RECOMMENDATION: Health care professionals should prescribe testosterone therapy only for men with low testosterone levels caused by certain medical conditions and confirmed by laboratory tests. Health care professionals should make patients aware of the possible increased cardiovascular risk when deciding whether to start or continue a patient on testosterone therapy. Patients using testosterone should seek medical attention immediately if symptoms of a heart attack or stroke are present, such as chest pain, shortness of breath or trouble breathing, weakness in one part or one side of the body, or slurred speech.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program:

  • Complete and submit the report Online: www.fda.gov/MedWatch/report
  • Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[03/03/2015 – Drug Safety Communication – FDA]”

Previous MedWatch Alert:

[01/31/2014 – Drug Safety Communication – FDA]

Last week, the pharmaceutical company, Takeda, was ordered to pay $1.3 million in punitive damages to a former Philadelphia schoolteacher who “argued the drugmaker’s Actos diabetes medicine caused his bladder cancer”, Japan Times writes.

Only a few days earlier, that man was awarded over $2.3 million in compensatory damages.

According to that Japan Times article, this was the “fifth Actos patient to convince a jury that Takeda’s former top-selling drug causes bladder cancer. Last year, a federal jury in Louisiana ordered Takeda and Eli Lilly & Co., which at one time sold Actos in the U.S., to pay $9 billion in punitive damages to a shopkeeper who blamed his cancer on the drug. That award was cut to $36.8 million.”

So far, over 8,000 Actos lawsuits have been filed in the United States over the drug’s alleged undisclosed connection with increased risk for bladder cancer, and many of those cases have been consolidated before federal courts.

JT: “Takeda argued in court filings the company properly vetted the drug and included all required warnings on its safety label. It has battled former users’ claims in trials across the country starting in 2013.”

Bloomberg News explains that the Philadelphia schoolteacher was compensated $300,000 for medical expenses and $2 million for pain and suffering after Takeda “failed to properly warn [his] doctors about Actos’s cancer risks.”

Of course, this is still a relatively insignificant company for the largest drug company in Asia, generating $16 billion in revenue since the 1999 Actos release.

Bloomberg: “The Pennsylvania case is Kristufek v. Takeda Pharmaceuticals America Inc., Philadelphia Court of Common Pleas. The consolidated Actos case in Louisiana is In Re Actos (Pioglitazone) Products Liability Litigation, 11-md-02299, U.S. District Court, Western District of Louisiana (Lafayette).”

In recent years, a new anticoagulant drug called Xarelto (rivaroxaban) has been found by the FDA to increase the risk for major bleeding events over other drugs in its class.  And unlike other drugs in its class, the manufacturer does not recommend regular blood testing, a simple procedure which can lower the risk for major bleeding events by 40%.  Here, we discuss one piece of research titled “New oral anticoagulants in the treatment of acute venous thromboembolism – a systematic review with indirect comparisons.” on risks associated with Xarelto by an Austrian research team, published in VASA (2014).

The team studied over 27,000 patients using a variety of anticoagulants and measured the risk for stroke and bleeding events, finding that “Regarding occurrence of the composite bleeding endpoint, apixaban performed better than all other NOACs and dabigatran better than rivaroxaban and edoxaban.”

Continue Reading Doctors urge blood testing with Xarelto, despite Bayer’s claim it’s unnecessary

Titled “The potential role of anticoagulant therapy for the secondary prevention of ischemic events post-acute coronary syndrome”, a piece by A.C. Camuglia et al. (published in Current Medical Research and Opinion – August, 2014) from Royal Brisbane and Women’s Hospital and the University of Queensland (Queensland , Australia) reviews the safety of an anticoagulant drug called Xarelto.  Recently, a number of studies have indicated that this blood thinner carries a higher risk for major bleeding events than others in its class.

The team writes, “The use of dual antiplatelet therapy has led to a substantial reduction in ischemic events post-acute coronary syndrome (ACS). Despite this, recurrent event rates remain high. Recent research has combined antiplatelet with anticoagulant therapy to reduce recurrent event rates further”, noting that while “Compared with standard medical therapy, rivaroxaban demonstrated improved efficacy outcomes and significantly reduced mortality after an ACS. Although clear benefits of novel oral anticoagulants post-ACS have been proven, concerns regarding bleeding are still a barrier to widespread use.” (emphasis added)
Continue Reading Xarelto lawsuits cite studies indicating higher risk for bleeding than Bayer reports

Here, we discuss a study titled “Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease participating in the ROCKET AF trial.”, published in European Heart Journal this year by G. Breithardt and a team of German researchers.  This study aimed to further evaluate the safety of Xarelto (rivaroxaban), an anticoagulant drug linked to increased risk for major bleeding events.

[Click here to read safety communications regarding Xarelto from the FDA]

The team writes, “Among 14 171 patients, 2003 (14.1%) had [significant vascular disease (SVD)]; they were older and had more comorbidities than patients without SVD,” and “The rate of stroke or systemic embolism with rivaroxaban vs. warfarin was consistent among patients with SVD [2.01 vs. 2.43%; hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.55-1.27] and without SVD (1.96 vs. 2.22%; HR 0.89, 95% CI 0.75-1.07; interaction P = 0.76).”

However, Breithardt et al. (2014) also found that “rates of major and non-major clinically relevant bleeding with rivaroxaban vs. warfarin were higher in patients with SVD (19.8% rivaroxaban vs. 16.8% warfarin; HR 1.25, 95% CI 1.05-1.49) vs. those without (14.2% rivaroxaban vs. 14.1% warfarin; HR 1.01, 95% CI 0.94-1.10; interaction P = 0.034), even when controlling for risk factors and potential confounders.” (emphasis added)

Continue Reading Study shows Xarelto carries higher risk for bleeding than industry standard

In recent years, a number of studies have shown that the anticoagulant drug Xarelto (rivaroxaban) is linked to increased risk for major bleeding events.  Here, we discuss one such study, titled, “Anticoagulant-related gastrointestinal bleeding-could this facilitate early detection of benign or malignant gastrointestinal lesions?” and published in the August, 2014 edition of Annals of Medicine by A. Clemens et al.

This team states “The higher incidence of gastrointestinal (GI) bleeding with the non-vitamin K oral anticoagulants (NOACs) may be related to pre-existing malignancies; diagnostic measures triggered by these bleedings could lead to early detection of these malignancies.”

For this study, the team “retrieved the preferred terms on GI bleeding and GI cancer reported as adverse events (AEs) from phase III studies in patients with atrial fibrillation for each NOAC on ClinicalTrials.gov” and “analyzed the RE-LY trial database.”

Results showed that the risk for bleeding was different with different drugs: “dabigatran 110 mg b.i.d. (D110: 1.42% versus 1.37%), dabigatran 150 mg b.i.d. (D150: 1.93% versus 1.37%), rivaroxaban (3.52% versus 2.68%), and apixaban (1.93% versus 1.59%), compared with warfarin, respectively.” (emphasis added)
Continue Reading 2014 – More Research Shows Xarelto Linked to Major Bleeding Events

Recently, studies have shown that the anticoagulant drug Xarelto (rivaroxaban) is linked to a dramatically increased risk for major bleeding events compared to other drugs in its class.  Here, we discuss one such piece of research, titled “New oral anticoagulants in acute coronary syndrome: is there any advantage over existing treatments?”, published in the September, 2014 edition of International Cardiovascular Research Journal by a team of Italian researchers led by A. Messori.

This team states that their study “re-examined the studies published thus far on this topic to evaluate the effectiveness of dual antiplatelet therapy in comparison to some of these new approaches (mainly, ticagrelor + aspirin and dual therapy plus a new oral anticoagulant [NOAC]; i.e., “triple therapy”).”  To perform this study, the team evaluated and analyzed a number of previously-conducted studies with statistics to get a better overall picture of this risks and benefits of anticoagulant use.
Continue Reading 2014 – Researchers Cite Xarelto Bleeding Risk

Recently, the anticoagulant drug Xarelto (rivaroxaban) (Bayer Pharmaceuticals, Inc.) has been linked to an increased risk for major bleeding events, prompting a number of Xarelto lawsuits.  In August 2014, medical researcher Eugene Yang published a piece in Vascular Health and Risk Management titled “A clinician’s perspective: novel oral anticoagulants to reduce the risk of stroke in nonvalvular atrial fibrillation – full speed ahead or proceed with caution?”, exploring the safety of several anticoagulant drugs.  Here, we will discuss that research.

Yang states, “The aim of this review is to examine this indication from a clinician’s perspective, highlighting efficacy and safety results from the major trials with these novel oral agents. Clinical issues regarding bleeding, monitoring, and reversal are discussed, along with requirements to consider when interrupting treatment with a novel oral anticoagulant for the purpose of transitioning to another anticoagulant and prior to cardioversion, ablation, percutaneous coronary intervention, or emergency surgery.”

First, Yang found that patients using Xarelto only spend an average of 55% of time within the proper therapeutic window, the lowest of all anticoagulants reviewed.  Many doctors believe that if a patient spends less than 60% of the time in that therapeutic window, more harm than good is done.  It is vital to stay in that window, for too little drug places a patient at risk for stroke, and too much places a patient at risk for internal bleeding, which can be fatal.

Continue Reading 2014 – Study shows Xarelto more dangerous than other drugs in its class

In the United States alone, about four million prescriptions for anticoagulant drugs are filled each year.  With the use of each of these drugs comes the risk for internal bleeding, but not all drugs are created equal.  One such drug is Xarelto (rivaroxaban), and currently, the Xarelto Black Box Warning fails to adequately inform users of the increased risk for major bleeding events, higher than the risk linked to similar drugs, Xarelto lawsuits are being filed against Bayer Pharmaceuticals, Inc., Xarelto’s manufacturer.

In September 2014, the Journal of Cardiology published an article titled “Clinical usefulness of measuring prothrombin time and soluble fibrin levels in Japanese patients with atrial fibrillation receiving rivaroxaban.”, reviewing the safety of Xarelto.

The Japanese study team that wrote the article states, “Rivaroxaban is currently used to prevent stroke in patients with atrial fibrillation” and warns “Measuring coagulation function may help clinicians to understand the effects of this drug and the associated risk of bleeding.”

To review Xarelto, the team administered Xarelto to “136 patients with non-valvular atrial fibrillation” with an average age of 75. Results showed that “In Japanese patients with non-valvular atrial fibrillation receiving rivaroxaban, a prolonged peak PT (≥20s) could indicate increased risk of bleeding, and both trough and peak SF levels were reduced relative to baseline.”

Continue Reading 2014 – Xarelto linked to higher risk for bleeding