Drug Injury Watch

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

(Posted by Tom Lamb at DrugInjuryWatch.com)

Depakote and Depakene are prescription medicines from AbbVie Inc. (formerly Abbott) used:

• to treat manic episodes associated with bipolar disorder
• alone or with other medicines to treat:
     • complex partial seizures in adults and children 10 years of age and older
     • simple and complex absence seizures, with or without other seizure types
• to prevent migraine headaches

A Black Box Warning added in February 2013 to Package Insert, or label, for Depakote and Depakene states:

FETAL RISK

Valproate can cause major congenital malformations, particularly neural tube defects (e.g., spina bifida). Valproate should not be administered to a woman of childbearing potential unless the drug is essential to the management of her medical condition. This is especially important when valproate use is considered for a condition not usually associated with permanent injury or death (e.g., migraine)....

More information about the February 2013 warnings about fetal risks associated with Depakote and Depakene, particularly neural tube defects and other major malformations, can be found at these sections of the Depakote / Depakene Prescribing Information, or label, which were added to the label in May 2013:

5.2 Use in Women of Childbearing Potential

5.3 Birth Defects and Neurobehavioral Adverse Effects

In addition, at the Patient Counseling Information part of the Depakote / Depakene Package Insert (also called Prescribing Information) at Section 17.3, Birth Defects and Neurobehavioral Development Adverse Effects, there is this statement:

Prescribers should inform pregnant women and women of childbearing potential that use of Depakote during pregnancy increases the risk of birth defects and adverse effects on neurobehavioral development.

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More recently, in May 2013 the FDA issued this Safety Announcement, "FDA Drug Safety Communication: Valproate Anti-seizure Products Contraindicated for Migraine Prevention in Pregnant Women due to Decreased IQ Scores in Exposed Children", which included the following important and updated warning information about Depakote and Depakene:

The U.S. Food and Drug Administration (FDA) is advising health care professionals and women that the anti-seizure medication [Depacon (valproate sodium)] and related products, [Depakene and Stavzor (valproic acid)] and [Depakote, Depakote CP, and Depakote ER (divalproex sodium)], are contraindicated and should not be taken by pregnant women for the prevention of migraine headaches. Based on information from a recent study, there is evidence that these medications can cause decreased IQ scores in children whose mothers took them while pregnant.1 Stronger warnings about use during pregnancy will be added to the drug labels, and valproate’s pregnancy category for migraine use will be changed from "D" (the potential benefit of the drug in pregnant women may be acceptable despite its potential risks) to "X" (the risk of use in pregnant women clearly outweighs any possible benefit of the drug)....

FDA previously communicated initial findings about this risk in a June 2011 Drug Safety Communication ["Children born to mothers who took Valproate products while pregnant may have impaired cognitive development"]. At that time, FDA also worked with valproate manufacturers to revise the drug labels after interim results from the NEAD study showed lower cognitive test scores at age 3 in children exposed to valproate compared to children exposed to other antiepileptic drugs.

According to a May 6, 2013 News Release, "FDA warns pregnant women to not use certain migraine prevention medicines -- Valproate products can lower IQ scores in children of mothers who used them during pregnancy":

The FDA is working with the manufacturers to make changes to the drug labels to reflect this new information and to change the pregnancy category for prevention of migraine headaches to category X (the drug's risks outweigh the drug's benefits for this use) from category D (the drug's benefits outweigh the drug's risks for this use). Valproate products will remain category D for the other two approved indications, epilepsy and manic episodes associated with bipolar disorder.

We will watch for the FDA-mandated drug label revision for Depakote, Depakene, and related products by the drug company AbbVie regarding the lower IQ risk for children whose mother used these medications during pregnancy.

P.S.  "Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study"  (Lancet Neurology, March 2013)  

(6/10/13)

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

Drug Injury Case Evaluation - Free & Confidential  (Review done by attorney Tom Lamb) 

October 2012 Infuse Bone Senate Investigation Report Criticizes Medtronic For "Ghostwriting" Of Numerous Medical Journal Articles

Apparently In Order To Boost Sales Of Infuse Bone Growth Product, Medtronic Hid Medical Complications Such As Etopic Bone Growth And Male Sterility

(Posted by Tom Lamb at DrugInjuryWatch.com)

In the third part of this Medtronic Infuse series of articles we take a look back at the U.S. Senate Finance Committee investigation led by Senators Charles Grassley and Max Baucus prompted by The Spine Journal June 2011 edition featuring the Infuse safety issues as well as some investigative newspaper reports about Infuse.

We start with the June 21, 2011 document request letter sent by Grassley and Baucus to Omar Ishrak, the Chairman and CEO of Medtronic, Inc., which sets forth the reasons for this Senate investigation:

We are extremely troubled by press reports suggesting that doctors conducting clinical trials examining the safety and effectiveness of Infuse on behalf of Medtronic were aware that Infuse, a treatment commonly used in spinal surgery, may cause medical complications, but failed to report this in the medical literature.  This issue is compounded by the fact that some clinical investigators have substantial financial ties to Medtronic.

• Last year, the Milwaukee Journal Sentinelreported that a Medtronic-funded study published in 2004 found that 75% of bone morphogenetic protein 2 (BMP-2) patients experienced ectopic bone growth, where potentially harmful bone growth occurs outside of the fusion area.  The authors, who had financial ties to Medtronic, “concluded that ‘although not desirable,’” the ectopic bone growth “did not appear to have an ill effect on the patients.” However, in a separate 2008 study conducted by physicians without financial ties to Medtronic, “neurological impairment occurred” in five patients who had the same ectopic bone formation.  [“Complications rise along with off-label use of BMP-2,” Journal Sentinel, August 28, 2010.]

• According to the New York Times, a recent study “found that men treated with Infuse developed a condition that causes temporary or permanent sterility at a far higher rate than men who received a bone graft.”  This link to sterility was not reported in the original Medtronic-funded study.  [“New Study Links Spine Product From Medtronic to Risk of Sterility in Men,” New York Times, May 25, 2011.]  In addition, the Milwaukee Sentinel Journalreports that one author of the original study, Thomas A. Zdeblick, an orthopedic surgeon at the University of Wisconsin School of Medicine and Public Health, received “more than $23 million in various royalty payments from Medtronic since 2002.”  In addition, “Zdeblick also is the editor of the journal where two of the Infuse papers that failed to mention the link [to sterility] were published.”  [“Researchers get royalties, papers omit sterility link,” Journal Sentinel, May 25, 2011.]

We are also concerned that other severe side-effects of Infuse and similar bone-growth products developed by Medtronic may have been unreported or under-reported in clinical literature.  Reports have linked Infuse to potentially fatal swelling in the neck and throat, and radiating leg pain.  Concerns have also been expressed about a potential link to cancer.  ["Complications rise along with off-label use of BMP-2,” supra.]

Sixteen months later, the Senate Finance Committee issued its Staff Report on Medtronic's Influence on Infuse Clinical Studies (large PDF file) the findings of which included these points:

• Medtronic did not disclose its role in shaping 13 key studies of its Infuse Bone Graft product, which helped turn it into an $800-million product in 2011; and,
• Those studies, funded by Medtronic, failed to mention serious medical complications and side effects associated with the Infuse Bone Graft such as male sterility, infection, and increased back and leg pain.

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Free Infuse Bone Graft Case Evaluation 

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Here are two leading news reports about the context and significance of this October 2012 Infuse Senate investigation report:

1. "Medtronic Documents Spur New Questions"  (Wall Street Journal, 10/25/12)
2. "Medtronic's pull influenced Infuse articles, report finds"  (Minneapolis Star Tribune, 10/25/12)  

And as regards the 11 medical journal articles (and perhaps more) about the Infuse product which the Senate Finance Committee found that Medtronic had helped write, edit, and "shape", we refer you to this interesting January 2013 guest blog post published by the HealthNewsReview.org site, "Ghostwriting series part 2: Medtronic’s InFuse spinal fusion surgery product".

As may know, these are first two articles in this Meditronic Infuse in-depth series:

"Medtronic Infuse Bone Graft Efficacy And Safety Study By Yale: Widely Anticipated Results Are Set To Be Released In June 2013"

"Infuse Bone Graft: Medtronic-Funded Studies Essentially Ignored Serious Medical Complications And Side Effects Associated With Its Back Surgery Product"

Coming soon will be articles about (1) the FDA's rejection of Medtronic's related spine device, Amplify, (2) the reportedly 85% "off-label" use of the Medtronic Infuse Bone Graft product, and (3) patients who have suffered ectopic / excessive / unwanted bone growth, neurological impairment, and other severe side effects of the Infuse Bone Graft product.

Of course, if you have any tips or tidbits about the Infuse Bone Graft which you think deserve more attention, please send them to me by email for consideration to be included in one of these upcoming Infuse articles here on Drug Injury Watch.

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

Drug Injury Case Evaluation - Free & Confidential  (Review done by attorney Tom Lamb) 

Infuse Bone Graft: Medtronic-Funded Studies Essentially Ignored Serious Medical Complications And Side Effects Associated With Its Back Surgery Product

A 2009 - 2012 Series Of Investigative Reports Published By The Milwaukee Journal Sentinel Exposed Various "Problems" With How Medtronic Went About Boosting Sales Of Infuse

(Posted by Tom Lamb at DrugInjuryWatch.com)

In the second part of this Medtronic Infuse series of articles we want to bring to your attention some of the investigative news reports looking into the serious medical complications and side effects associated with the Infuse Bone Graft that were essentially ignored in Medtronic-funded studies.

As may know, we started this series with "Medtronic Infuse Bone Graft Efficacy And Safety Study By Yale: Widely Anticipated Results Are Set To Be Released In June 2013".

Reporter John Fauber, a news reporter for the Milwaukee Journal Sentinel, seems to be the journalist who should be credited most for exposing the several problematic aspects of how Medtronic has marketed its Infuse Bone Graft product over the years.

Here is a list of such investigative reports published by the Milwaukee Journal Sentinel from 2009 to 2012, ranging from the Infuse clinical trials to serious conflicts of interest and more:

Medical device maker paid UW surgeon $19 million

Thomas Zdeblick, an orthopedic surgeon at the University of Wisconsin-Madison, raised eyebrows three years ago when it was learned that he had been receiving $400,000 yearly from the medical device company. But yearly payments actually averaged about 10 times that figure.

Journal editor gets royalties as articles favor devices

In 2002, Thomas Zdeblick, a UW orthopedic surgeon who has pocketed millions of dollars in royalties from the spinal device maker Medtronic, took over as editor-in-chief of a medical journal about spinal disorders. It would be the beginning of a beautiful friendship.

Bone-fusion protein raises questions about doctors' financial stakes

The story of BMP-2 raises questions about whether doctors should be allowed to do clinical trial research involving products that might enrich them or the company they work for.

Doctors question journal articles

Over the last decade, a small group of surgeons has been enlisted by Medtronic to do research or write articles about the company's new spine surgery product. This year alone, many of those doctors received payments of hundreds of thousands to millions of dollars each in royalties for a variety of other Medtronic devices.

Researchers get royalties, papers omit sterility link

Since 2002, Medtronic and a group of doctors with financial ties to the medical device company were aware that a new biological agent used in back surgery was linked to sterility in men. But that crucial information was not revealed in medical journal articles written by those doctors.

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Free Infuse Bone Graft Case Evaluation 

Strictly Confidential, No Obligation.

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U.S. Senate panel probes Medtronic

A U.S. Senate committee has launched an investigation into reports that doctors with financial ties to the medical device company Medtronic were aware of serious complications with a lucrative spine surgery product yet failed to reveal those problems in medical journal articles.

Journal: Unreported side effects, disclosure failures with Medtronic back product

The entire issue of a medical journal is devoted to a scientific and financial expose of a product, the practices of the company that markets it and the financially conflicted doctors who tested and promoted it.

Articles leave pain in their wake

Patients' excruciating pain is at the center of a growing controversy surrounding the Medtronic and the spine surgery product Infuse that it markets.

Doctors didn't disclose spine product cancer risk in journal

Doctors paid millions of dollars by Medtronic failed to identify a significant cancer risk with the company's spine surgery product in a 2009 paper about results of a large clinical trial. The company and doctors had become aware of information on an additional cancer case, which pushed the concern to a critical level, at least two months before the paper was published, a Journal Sentinel/MedPage Today investigation found.

Medtronic paid millions to influential UW chairman

An orthopedic surgeon at the University of Wisconsin-Madison gets so much money from the medical device firm Medtronic that he is required to meet annually with his department chairman. But the chairman, Thomas Zdeblick, got more than 25 times that amount from Medtronic during the same time.

Senate panel says Medtronic workers ghostwrote papers

Medtronic marketing employees were secretly involved in drafting and editing favorable medical journal articles about the company's lucrative back surgery product, a U.S. Senate investigation reveals.

These Milwaukee Journal Sentinel articles were taken from the Side Effects page of JSOnline.com, the newspaper's web site, where you can find additional resources (such as documents and photos) pertaining to these Medtronic Infuse investigative reports.

We commend this newspaper and reporter John Fauber for developing this Infuse Bone Graft story of apparent corporate misconduct by Medtronic, which is still emerging as we wait for the release of the Yale Infuse Study currently scheduled to be released in June 2013.

P.S.  Part 3 of article series: "October 2012 Infuse Bone Senate Investigation Report Criticizes Medtronic For "Ghostwriting" Of Numerous Medical Journal Articles"  (5/22/13)

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

Drug Injury Case Evaluation - Free & Confidential  (Review done by attorney Tom Lamb)