Drug Injury Watch

With Zofran - Birth Defects Lawsuits Filed, How Will GlaxoSmithKline Update Its Drug Label To Comply With New FDA Rule Effective June 2015

New FDA Rule Requires Drug Company To Replace Current Simple Pregnancy Category Designation With A Summary Of The Risks Of Using Zofran During Pregnancy

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

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UPDATE:  Novartis and GlaxoSmithKline (GSK) have reportedly completed the final stages of GSK’s oncology portfolio buyout. As such, Novartis is now the responsible drug company for Zofran and would be making any Zofran label changes going forward.

(5/19/15)

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Starting earlier this year drug injury products liability lawsuits alleging birth defects caused by the use of Zofran (ondansetron) during pregnancy for so-called "morning sickness" have been filed against the pharmaceutical company GlaxoSmithKline (also known as GSK or Glaxo).

One standard contention found in the Zofran lawsuit Complaints filed to date is as follows:

GSK falsely and negligently represented to the medical community and expectant mothers, including Plaintiff and her providers, that:

a.   Zofran was safe and effective for treating pregnancy-related nausea;
b.   Zofran had been adequately tested and studied in pregnant women;
c.   Zofran use during pregnancy did not increase the risk of bearing children with birth defects; and,
d.   Zofran’s “Pregnancy Category B” designation established the safety and efficacy of Zofran for treating pregnancy-related nausea.

In December 2014 the FDA issued a new regulatory rule that seems to require GlaxoSmithKline in the next couple of months to make an important decision which may impact the Zofran lawsuits, those already filed and those that will be filed in the future.

In particular, it seems that Glaxo will need to decide what, if anything, it will disclose, i.e., admits to know, as regards the association between Zofran and birth defects such as congenital heart defects and cleft palate or lip.

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As regards this new FDA rule, which takes effect in June 2015, from this recent article, "FDA aims to dispel 'myth of the medication-free pregnancy'", published by the Chicago Tribune:

The revisions to prescription guidelines — the first since 1979 — will provide more up-to-date and specific information to doctors to help them identify the safest treatment options for common conditions during pregnancy, [said Dr. Katherine Wisner, a professor and psychiatrist at Northwestern University Feinberg School of Medicine, who advised the FDA on the changes], who specializes in maternal mood disorders.

The old system relied on letter grades of A,B,C, D and X — A for the most benign medications to X for off-limits. The new system is designed to give physicians more technical information when prescribing medications, said Sandy Walsh, an FDA spokeswoman.

The updated prescribing guidelines consist of three components. The first gives physicians information on dosing and risks to the fetus....

The letter labels were "confusing and overly simplistic," Wisner said.  "But now doctors and patients will have quality data to provide better answers. ... We're moving from a single letter to more practical guidelines."

In essence, for GlaxoSmithKline, the company will be required to remove the current Pregnancy Category B designation designation from its Zofran drug product labeling and instead: (1) summarize the risks of using Zofran during pregnancy; (2) discuss the medical as well as clinical data about Zofran supporting that summary; and, (3) describe relevant information to help health care providers make prescribing decisions and counsel women about the use of Zofran during pregnancy.

Here are links to the current Zofran Prescribing Information documents (accessed 4/28/15) for the various forms of that GSK drug currently approved by the FDA.

It will be interesting to check those Zofran drug label documents in a couple of months from now to see what revisions have been made by Glaxo to conform to this new FDA rule.

And it would not be a surprise if just how those Zofran label changes were made had something to do with the current Zofran - birth defects lawsuits.

 

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

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

Attention Deficit Hyperactivity Disorder Drugs Concerta And Ritalin Get New Warnings For Rhabdomyolysis In US And Priapism In Canada

Muscle-Wasting Side Effect "Rhabdo" Seems To Apply To Entire ADHD Class Of Drugs Given That April 2015 FDA Letter Was Sent To All Manufacturers

(Posted by Tom Lamb at DrugInjuryWatch.com)

We start in the US where an April 15 FDA letter to drug companies like Janssen Pharmaceuticals (regarding Concerta) stated that new safety information pertaining to the association between the use of stimulants used to treat Attention Deficit Hyperactivity Disorder (ADHD) and rhabdomyolysis, or "rhabdo" for short, should be added to the drug labels for ADHD medications such as these:

Adderall
Concerta
Focalin
Ritalin
Strattera
Vyvanse

According to the PubMed Health page for rhabdomyolysis, from the US National Library of Medicine:

Rhabdomyolysis is a condition in which damaged skeletal muscle tissue breaks down rapidly. Breakdown products of damaged muscle cells are released into the bloodstream. Some of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure.

Next we turn to an April 2015 Health Canada safety alert about methylphenidate products such as Concerta and Ritalin being associated with prolonged and painful erections -- a medical condition called priapism -- in male patients, including children.

From that Health Canada alert about Concerta and Ritalin:

Priapism is a very rare condition that has been reported during treatment with methylphenidate products, after increasing the dose, or stopping the product even for a short period of time. The prescribing information for methylphenidate products has been updated to include this information.

We will continue to watch for further developments concerning the safety profiles of popular ADHD drugs such as Adderall, Concerta, Ritalin, Strattera, and Vyvanse.

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

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

Diabetes Drugs Kombiglyze And Onglyza: Heart Failure Side Effect Seems To Be Valid, And FDA Notes There Is A Possible Increased Risk Of All-Cause Mortality

As Analysis Did Not Reveal Causes Of The Increase In Death Incidents, FDA Asks Its Advisory Committee To Discuss This Safety Issue At April 2015 Meeting

(Posted by Tom Lamb at DrugInjuryWatch.com)
 
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UPDATE: "AstraZeneca, Takeda Diabetes Drugs Should Warn of Risk" (4/15/15, Bloomberg)

(4/15/15)

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The AstraZeneca diabetes drugs Onglyza (saxagliptin) and Kombiglyze (saxagliptin plus metformin) will come under scrutiny at an April 14, 2015 FDA meeting according to early news reports about that upcoming event.
 
We previewed in this April 14, 2015 meeting of the FDA's Endocrinologic and Metabolic Drugs Advisory Committee in this article we wrote last month, "Cardiovascular Safety Issues For Onglyza And Kombiglyze Will Be Discussed At April 2015 FDA Advisory Committee Meeting".
 
Last Friday, April 10, FDA posted online their Briefing Material document for this Kombiglyze / Onglyza safety meeting (PDF file, 105 pages).

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As regards what that FDA staff document contained and its significance, from an April 10, 2015 Bloomberg news report, "AstraZeneca’s Diabetes Drug May Raise Death Risk, FDA Says":

AstraZeneca Plc’s type 2 diabetes drug Onglyza showed an increased risk of death in an analysis by U.S. regulators of a clinical trial on the heart effects of the treatment.  Food and Drug Administration staff said their analysis of deaths in the trial suggested patients using Onglyza experienced “significant or near-significant” increases in death from all causes, not just heart problems....
 
Since 2008, the FDA has asked manufacturers of drugs for type 2 diabetes to provide evidence the products don’t increase the risk of heart attack or other cardiovascular events.
 
Patients who use Onglyza also have a 27 percent increased risk of hospitalization for heart failure compared to those who were given a placebo, FDA staff said. The risk was first revealed in clinical trial results published in October 2013 in the New England Journal of Medicine ["Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus"].
 
Onglyza didn’t increase or decrease the rate of heart attack, stroke or death, according to the [New England Journal of Medicine (NEJM)] article.

That October 2013 NEJM article led to a FDA Safety Announcement several months later, as we reported in this earlier article, "Possible Link Between Heart Failure And Onglyza Diabetes Type 2 Drug Is Being Investigated By FDA, As Announced In February 2014".
 
We will be watching for any significant developments coming out of this April 2015 FDA Advisory Committee Meeting concerning the safety of Onglyza and Kombiglyze such as a possible label change for these AstraZeneca diabetes drugs.

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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  (Case review done by attorney Tom Lamb)

A 2004 Medical Journal Article Indicated A Possible Link Between The "Morning Sickness" Drug Use Of Zofran And Hypospadias

However, It Seems No Further Research About This Congenital Birth Defect Being Caused By Zofran Use During Pregnancy Has Been Done By GlaxoSmithKline

(Posted by Tom Lamb at DrugInjuryWatch.com)

So-called "morning sickness", or nausea and vomiting (NVP), is the most common medical condition of pregnancy, affecting more the 75% of all pregnancies to some degree.  In fact, severe NVP, or hyperemesis gravidarum, can be debilitating and require hospitalization.

For many years now, some women with morning sickness have been prescribed Zofran (ondansetron) and had babies born with birth defects and other congenital malformations.

Remarkably, Zofran is not even approved by the FDA as a treatment to reduce morning sickness when women are pregnant. Rather, this GlaxoSmithKline drug has been approved by FDA for the prevention of nausea or vomiting associated with chemotherapy and radiotherapy as well as in some instances following surgery.

As far back as 2004 some medical researchers have noted that while Zofran is being used for morning sickness, or NVP, there have been no sufficient medical studies examining its safety in pregnancy.

From "The safety of ondansetron for nausea and vomiting of pregnancy: a prospective comparative study", published by the medical journal BJOG: an International Journal of Obstetrics and Gynaecology in September 2004, we find this rather alarming (one would think) statement about that situation:

[Zofran (ondansetron)] was never intended or labeled as such to be a treatment for NVP. Consequently, there is a paucity of data in the literature on the safety of [Zofran (ondansetron)] for the treatment of NVP: there are three case reports and one small study comprised of 15 subjects with severe NVP (hyperemesis gravidarum) who were compared with women taking promethazine.  [footnotes omitted]

Coincidentally, the two medical journal articles about those case reports and that small study were published in the same year GlaxoSmithKline (GSK) lost its patent protection for Zofran -- and when its equivalent, ondansetron, first became available in the US, and started being sold by generic drug company competitors.

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While the lack of a sufficient Zofran pregnancy-use safety study was certainly pointed out by the authors of that 2004 medical journal article, and they identified hypospadias as a specific "major malformation" which might be associated with Zofran use, it seems that little if any such safety research has been done by the drug company GSK to date -- despite those authors' clear call for such.

From that BJOG medical journal article:

... in the [Zofran (ondansetron)] group, there were three cases of hypospadias, which fit our criteria for major malformation because they required surgery.  This is an increase in the rate of hypospadias in the general population (though not statistically significant), where this abnormality occurs in approximately 1 in every 300 males.  Of note however, none of these hypospadias were categorized as severe, two of the three were described by the child’s attending physician in the report as minor and one was described as moderate. Our sample size lacked power to show this apparent sixfold increase in this anomaly, thus, was not statistically significant. This increase in the rates of hypospadias was not shown in animal studies.  More studies are required to achieve significant power to address any potential association between [Zofran (ondansetron)] and hypospadias.  [footnotes omitted]

Meanwhile, as set forth in this earlier article, "Zofran Associated With Birth Defects When Used During Pregnancy As An 'Off-Label' Morning Sickness Treatment":

In 2012, the U.S. Department of Justice reached a $3-billion settlement with GlaxoSmithKline after the government alleged the company promoted the off-label uses of several drugs, including Zofran, the company’s brand-name version of ondansetron.

Court documents alleged the company gave doctors kickbacks to prescribe the drug for morning sickness and disseminated false information about Zofran’s safety and effectiveness.

We are currently investigating possible drug injury lawsuits against GlaxoSmithKline for cases where Zofran used by pregnant women resulted in birth defects, congenital malformations, or deformities in children born to those women.

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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  (Case review done by attorney Tom Lamb)