Drug Injury Watch

Significantly Increased Risk Of Autism Spectrum Disorder (ASD) In Children Whose Mothers Used Depacon / Depakene / Depakote During Their Pregnancy

August 2014 Label Change By AbbVie Inc. (formerly Abbott) For These Valproate Migraine, Epilepsy/Seizure, And Bipolar Medications Was Done Rather Quietly

(Posted by Tom Lamb at DrugInjuryWatch.com)

Without much notice, e.g., no FDA Drug Safety Communication was issued, in August 2014 the Prescribing Information, or drug labels, for Depakote, Depakote CP, and Depakote ER (divalproex sodium), Depacon (valproate sodium), and Depakene (valproic acid) were updated by the drug company AbbVie Inc. (formerly Abbott) to add a warning about the potential risk for autism spectrum disorders (ASD).

In the label approved by the FDA on August 20, 2014 for Depakote (accessed 9/25/14), this new warning about autism spectrum disorders can be found at Section 8.1 Pregnancy:

An observational study has suggested that exposure to valproate products during pregnancy may increase the risk of autism spectrum disorders. In this study, children born to mothers who had used valproate products during pregnancy had 2.9 times the risk (95% confidence interval [CI]: 1.7-4.9) of developing autism spectrum disorders compared to children born to mothers not exposed to valproate products during pregnancy. The absolute risks for autism spectrum disorders were 4.4% (95% CI: 2.6%-7.5%) in valproate-exposed children and 1.5% (95% CI: 1.5%-1.6%) in children not exposed to valproate products. Because the study was observational in nature, conclusions regarding a causal association between in utero valproate exposure and an increased risk of autism spectrum disorder cannot be considered definitive.

The medical study referenced in this new "valproate drugs used during pregnancy - risk of autism spectrum disorders" warning seems to be the subject of this article, "Prenatal Valproate Exposure and Risk of Autism Spectrum Disorders and Childhood Autism", which was published by the Journal of the American Medical Association (JAMA) in April 2013. From the Conclusions section of this JAMA medical journal article:

Maternal use of valproate during pregnancy was associated with a significantly increased risk of autism in the offspring, even after adjusting for parental psychiatric disease and epilepsy. For women of childbearing potential who use antiepileptic medications, these findings must be balanced against the treatment benefits for women who require valproate for epilepsy control.

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And for a better understanding of this still relatively "new" Depacon / Depakene / Depakote - autism side effect issue, we refer you to the very informative National Institute of Mental Health (NIMH) web page "What Is Autism Spectrum Disorder?":

Autism spectrum disorder (ASD) is characterized by:

• Persistent deficits in social communication and social interaction across multiple contexts;
• Restricted, repetitive patterns of behavior, interests, or activities;
• Symptoms must be present in the early developmental period (typically recognized in the first two years of life); and,
• Symptoms cause clinically significant impairment in social, occupational, or other important areas of current functioning.

The term “spectrum” refers to the wide range of symptoms, skills, and levels of impairment or disability that children with ASD can have. Some children are mildly impaired by their symptoms, while others are severely disabled....

Previously, in a May 2013 post, we reported that children born to mothers who took any of the valproate medications -- valproate sodium (Depacon), divalproex sodium (Depakote, Depakote CP, and Depakote ER), valproic acid (Depakene and Stavzor), and their generics -- may have other serious side effects:

Depakote Or Depakene Taken During Pregnancy May Cause Congenital Malformations Or Birth Defects Such As Neural Tube Defects Like Spina Bifida 

In Addition, There Are FDA Warnings That Using Depakote Or Depakene While Pregnant May Put Child At Risk For Having A Lower IQ Score Later In Life

As regards lawsuits and legal claims, we expect that the Depacon / Depakene / Depakote drug injury litigation which previously was focused on certain types of birth defects or congenital malformations will expand to include cases of autism spectrum disorder (ASD) and autism.
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DrugInjuryLaw.com: Current Legal And Medical Information About Prescription Drug Side Effects (All website content by attorney Tom Lamb)

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Testosterone Drugs FDA Meeting In September 2014 Reveals That The Safety Of Products Like Axiron, AndroGel, And Testim Is Uncertain Or Unknown At Present Time

Key Advisory Panel Member Concedes It Is Medically Plausible That Testosterone Replacement Therapy Can Be Associated With Heart Attacks / Strokes Side Effects

(Posted by Tom Lamb at DrugInjuryWatch.com)

On September 17, 2014 members of the FDA's Bone, Reproductive and Urologic Drugs and Drug Safety and Risk Management advisory panels considered the issue of whether the popular testosterone products Axiron, AndroGel, and Testim, as well as other so-called "Low-T" drugs, are safe.  Not surprising -- but certainly unsettling -- was the outcome of their discussions, which was essentially that for most current users of testosterone replacement therapy (TRT) medications we do not know and cannot know, because no safety study has been done, yet.

From a September 18, 2014 Healio EndocrineToday report, "FDA committees near-unanimous on need to investigate testosterone therapies":

A key presentation by Shalender Bhasin, MD, of Harvard Medical School, with advisory board seats for two of the sponsors, broached the biggest topic of concern in the room during a presentation on cardiovascular events and testosterone therapies.

“Testosterone’s effects in preclinical and clinical models are diverse,” Bhasin said. “Some effects are beneficial, and some may be potentially deleterious.”

Bhasin conceded biologic plausibility for the association of testosterone with cardiovascular events. He presented data from a meta-analysis demonstrating lower testosterone levels were associated with higher all-cause mortality, epidemiologic studies showing mixed results and a small randomized placebo-controlled trial showing increased cardiovascular events with therapy.

“It’s important to distinguish between classical hypogonadism and age-related decline,” Bhasin said. “In young men with classical hypogonadism, testosterone replacement therapy improves symptoms with low adverse event frequency. In older men, with age related decline or frailty, neither benefits nor risks have been clearly demonstrated.”

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And from a September 18 Medscape Medical News article, "FDA Advisory Panel Urges Restrictions on Testosterone Use":

Regarding the safety question, Tobias Gerhard, PhD, from the Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, said: "The evidence regarding cardiovascular safety is obviously very insufficient. We need more data. At this point, I don't think there's evidence for a clear causal association, but I believe we do have a signal of reasonable strength."

Given the magnitude of off-label use "and lack of strong data on effectiveness in this population, I think it's important to include something about cardiovascular safety in the label. Maybe not to the level of black box, but certainly that there are serious concerns that have not yet been adequately addressed," he added....

Toby C. Chai, MD, professor and vice chair of the department of urology at Yale University School of Medicine, New Haven, Connecticut, said, "For a population it was not originally intended to be used [in]…if we want to look at reality we have to do safety studies....Whether it should be randomized or observational, I think we'll be prospectively looking at those cardiovascular risks."

We have to wait to see what regulatory action the FDA will take, if any, concerning the possible increased risks of heart attacks and strokes that some link to Axiron, AndroGel, Testim, and other "Low-T" drugs.

One can say, however, that despite this September FDA Advisory Committee meeting, many questions about the safety of these testosterone drugs remain unanswered, still.

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DrugInjuryLaw.com: Current Legal And Medical Information About Prescription Drug Side Effects (All website content by attorney Tom Lamb)

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Summer 2014 Update YAZ / Yasmin / Ocella / Gianvi Litigation: Bayer Reports On Total Settlements And Number Of Pending Claims

Perhaps The Slow-Going Over Past Year Will Be Changed By Upcoming Mediations With Two Special Masters Appointed Recently By Judge Herndon

(Posted by Tom Lamb at DrugInjuryWatch.com)

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UPDATE: December 2014 YAZ / Yasmin Litigation Update: Still Over 2000 DVT And/Or PE Cases Not Settled According To Bayer's Most Recent Financial Report

(12/15/14)

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In their Stockholders' Newsletter Financial Report as of June 30, 2014, Second Quarter of 2014 (PDF) Bayer informs at page 54 that as of July 2, 2014:

• Settlements with about 8,900 claimants for total of $1.8 billion;
• The number of pending claims with deep vein thrombosis (DVT) and/or pulmonary embolism (PE) -- the "venous clot injuries" -- is approximately 2400; and,
• There are an estimated 2,600 claims with other alleged drospirenone (DRSP) related injuries, such as arterial clots.

Significant or not, in their latest quarterly report Bayer continues to only allude to YAZ, Yasmin, Ocella, and Gianvi cases -- while still making no mention of there being any Beyaz and Safyral cases filed (which there are, in fact).

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So where do things stand in comparison to our last article about the Bayer DRSP birth control pills litigation? From just looking below at the title and sub-title of this June 2014 item we can see that more new blood clot cases have been filed than there have been older cases settled, using Bayer's numbers.

About 2000 YAZ / Yasmin / Ocella / Gianvi Blood Clot Cases Are Still Not Settled More Than Two Years After Bayer Began Settlement Mediations 

Bayer Reports That As Of April 8, 2014 Settlement Negotiations Have Resolved "approximately 8,560 claimants in the U.S. for a total amount of about US$1.74 billion"

One hopes that the August 28 Case Management Order wherein Judge David Herndon, who is presiding over the Yasmin / YAZ federal court MDL consolidation, appointed two special masters "for the purpose of mediating settlement" will serve to move this litigation toward a total resolution at a faster pace than has been the experience of this past year.

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DrugInjuryLaw.com: Current Legal And Medical Information About Prescription Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free & Confidential  (Legal case review done by attorney Tom Lamb) 

Eliquis And Xarelto, Like Pradaxa, Linked To Serious Bleeding Events Due To Fact No Antidote Available

Hemorrhages And Gastrointestinal (GI) Bleeds Are Eliquis And Xarelto Side Effects That Can Cause Deaths

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

Eliquis and Xarelto are new anticoagulants, i.e., blood thinners, that -- unlike Coumadin (warfarin) -- do not require regular INR monitoring and dose adjustments.

Eliquis (apixaban) and Xarelto (rivaroxaban) are "factor Xa" drugs and they work differently from warfarin. These new blood thinners reduce thrombin production by inhibiting an enzyme called factor Xa instead of inhibiting vitamin K's clotting ability.

A real danger or problem that Eliquis and Xarelto share with another new blood thinner drug, Pradaxa (dabigatran), however, is the absence of an approved drug that can reverse their effects.  That is, at the present time there is no antidote to stop serious bleeding events.

From a July 23, 2014 MedPage Today article, "Monitoring, Dose Adjustment for Pradaxa?", we get this important discussion about the safety issues surrounding Eliquis and Xarelto:

While there's no extensive data published to prove it, variability in blood concentrations is likely for the other newer oral anticoagulants -- such as apixaban (Eliquis), rivaroxaban (Xarelto), and edoxaban (Savaysa) -- too, according to a letter from Boehringer employee Paul Reilly, PhD, and RE-LY study authors in the Journal of the American College of Cardiology last month responding to criticism that data on dabigatran and plasma levels had been suppressed.

That is a point worth pursuing, Cohen argued.

"Rivaroxaban and apixaban were also marketed on the theme that plasma level dose adjustment was not needed, as it is with warfarin," she wrote. "More systematic and independent study is needed to establish what price, in terms of preventable hemorrhage and death, is being paid for each of the new drugs in the name of ease of use."

 

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And who is this "Cohen" person?

For the answer to that question and some background as well as insight on this renewed drug safety controversy concerning Pradaxa, Xarelato, and Eliquis, we turn to a July 23, 2014 article by Larry Husten, "More Questions Raised About Boehringer Ingelheim's Pradaxa":

Once again dabigatran (Pradaxa) has raised the wrath of the critics. Several articles and an editorial published today in The BMJ raise more questions and concerns about the drug, which is the first of the new oral anticoagulants. Relying on new evidence along with previously disclosed data, Deborah Cohen, the  investigations editor for The BMJ, casts doubt on the reliability of the data supporting the drug as well as the behavior and decisions of regulatory authorities, trial investigators, and employees  of Boehringer Ingelheim, the drug’s manufacturer. Although the articles focus on dabigatran, it is entirely possible that similar questions may also be raised about other new oral anticoagulants, including rivaroxaban (Xarelto, Johnson & Johnson) and apixaban (Eliquis, Pfizer and Bristol-Myers Squibb).

For those of you who want to read more in-depth about the various issues associated with serious bleeding side effects linked to Pradaxa, as well as Xarelto and Eliquis, below are the BMJ medical journal materials.

First, the Feature items:

• Dabigatran: how the drug company withheld important analyses
  Deborah Cohen
• Concerns over data in key dabigatran trial
  Deborah Cohen

Next, the Analysis item:

• Dabigatran, bleeding, and the regulators
  Thomas J Moore, Michael R Cohen, and Donald R Mattison

And finally, the Editorial item:

• The trouble with dabigatran
  Blake Charlton and Rita Redberg

We will continue to monitor the safety profiles of Eliquis and Xarelto as well as watch to see whether drug injury and death lawsuits concerning these new blood thinner products follow along the lines of the Pradaxa litigation, which was settled by Boehringer Ingelheim earlier this year.

 

DrugInjuryLaw.com: Current Legal And Medical Information About Prescription Drug Side Effects  (All website content by attorney Tom Lamb)

Drug Injury Case Evaluation - Free & Confidential  (Legal case review done by attorney Tom Lamb)