Drug Safety Developments

Only Two out of Three Classes of Diabetes Drugs Help Reduce the Risk of Death

 

Written by: Heather Helmendach, Legal Assistant 
Law Offices of Thomas J. Lamb, P. A.

 

Class Comparisons

Three popular types of diabetes drugs include sodium-glucose cotransporter (SGLT-2) inhibitors, dipeptidyl peptidase (DPP-4) inhibitors, and incretin mimetics (also referred to as glucagon-like peptide (GLP-1) agonists).

The following table provides a list of some of these types of drugs:

SGLT-2 Inhibitors	SGLT-2 / DPP-4 Inhibitors	DPP-4 Inhibitors / Incretin Mimetics	Incretin Mimetics
Invokana	Glyxambi	Onglyza	Byetta
Invokamet (XR)	Qtern	Januvia	Bydureon
Farxiga		Janumet (XR)	Victoza
Xigduo XR		Kazano	Juvisync
Jardiance		Oseni
Synjardy (XR)		Tradjenta
Steglatro		Jentadueto
Steglujan		Nesina
Segluromet		Kombiglyze XR

 

Study Results

A recent study compared these three types of diabetes drugs in order to determine their effect on "all-cause mortality" in patients with type 2 diabetes.  While all three classes lowered blood sugar levels, only two reduced the risk of death.  

The researchers found the use of SGLT-2 inhibitors and incretin mimetics was associated with lower mortality rates than DPP-4 inhibitors.  More specifically, SGLT-2 inhibitors were associated with a 21% reduction in cardiovascular-related death, and incretin mimetics were associated with a 15% reduction.

However, DPP-4 inhibitors did not reduce the risk of death when compared to a placebo or no treatment at all.

One of the researchers acknowledged that further studies are needed to confirm their findings, and tracking participants for a longer period of time would be beneficial.

 

Side Effects

While the study did not aim to identify any particular harmful side effects directly caused by the drugs, numerous side effects have been associated with these classes of drugs in other studies.  As such, one must wonder how the benefits of these drugs weigh against their potentially-fatal side effects.

For example, users of SGLT-2 inhibitors have experienced the following side effects:

• Diabetic Ketoacidosis (DKA)
• Ketoacidosis
• Ketosis
• Leg Amputation
• Foot or Toe(s) Amputation
• Acute Kidney Injury

• Kidney Failure / Renal Failure
• Kidney Damage
• Pyelonephritis (kidney infection)
• Urosepsis (blood infection)
• Urinary Tract Infection (UTI)
• Bladder Cancer

As for DPP-4 inhibitors, these side effects have been observed:

• Heart Failure
• Kidney Failure / Renal Failure
• Kidney Problems
• Decreased Renal Function 
• Cerebral Infarction / CVA / Stroke
• Myocardial Infarction (MI) / Heart Attack

• Acute Pancreatitis
• Severe Joint Pain
• Inflammatory Bowel Disease (IBD)
• Ulcerative Colitis
• Crohn's Disease
• Rhabdomyolysis

Lastly, incretin mimetics carry a potential risk of pancreatic cancer.

Going forward, we will continue to monitor the medical literature concerning the side effects associated with these three classes of diabetes drugs.

In the meantime, we encourage you to fill out one of our free case evaluations concerning SGLT-2 inhibitors, DPP-4 inhibitors, and incretin mimetics.

 

 

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FDA Restricts Sales of Essure Permanent Birth Control Device

 

Written by: Heather Helmendach, Legal Assistant 
Law Offices of Thomas J. Lamb, P. A.

 

Background

Essure is a form of permanent birth control that requires the implantation of a small device within the female reproductive system.  It was originally approved by the FDA in 2002, and approximately 750,000 women worldwide have received Essure since its approval.  Given that the device is meant to be permanent, it is not typically removed unless necessitated by complications.

Bayer is the manufacturer of this contraceptive device, and has received pressure from the U.S. Food and Drug Administration to increase warnings for Essure in light of the increasing number of adverse event reports that have been submitted within the past several years.

 

Previous Warnings

On November 15, 2016, the FDA approved a revised label for Essure that included a boxed warning and a Patient Decision Checklist (p. 19 of linked document).  A boxed warning, sometimes called a "Black Box Warning" is the most serious warning that can be included with a product.  

This new Essure warning reads:

WARNING: Some patients implanted with the Essure System for Permanent Birth Control have experienced and/or reported adverse events, including perforation of the uterus and/or fallopian tubes, identification of inserts in the abdominal or pelvic cavity, persistent pain, and suspected allergic or hypersensitivity reactions. If the device needs to be removed to address such an adverse event, a surgical procedure will be required. This information should be shared with patients considering sterilization with the Essure System of Permanent Birth Control during discussion of the benefits and risks of the device. [Emphasis added]

By adding this warning and including the checklist, the FDA hoped to ensure that women were adequately informed of the possible risks of undergoing implantation of this medical device.  However, they recently determined that some women are still not being thoroughly informed of the risks, and decided further action was necessary.

 

New Requirements

On April 9, 2018, the FDA restricted the sale of Essure, and sent a letter to Bayer requiring them to make further changes to the current label for this contraceptive device.

Per the new FDA requirements, women must now read and sign a brochure that provides detailed information on the risks of Essure before they can undergo the implantation procedure.

Furthermore, sale and distribution of Essure is limited to healthcare providers who agree to review the “Patient-Doctor Discussion Checklist – Acceptance of Risk and Informed Decision Acknowledgement” with patients.  Both the patient and their doctor must also sign the checklist before the Essure implantation procedure can take place.

Given that Essure sales dropped 70% after increased warnings were required by the FDA in 2016, and Bayer stopped selling Essure outside of the U.S. last year for "commercial reasons," it will be interesting to see if the product will vanish from U.S. markets in the wake of these new warnings and requirements.

We will continue to monitor the medical literature for updated information on Essure and its associated risks, and report on significant developments.

In the meantime, we encourage you to complete a Free Essure Case Evaluation if you or someone you know has experienced severe complications as a result of the Essure permanent contraceptive device.

 

 

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FDA Provides Updated Number of Breast Implants Lymphoma Cancers

 

Written by: Heather Helmendach, Legal Assistant 
Law Offices of Thomas J. Lamb, P.A.

 

About BIA-ALCL

The U.S. Food and Drug Administration (FDA) has been aware of the possible connection between breast implants and breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) since 2011. 

This condition is a rare type of non-Hodgkin’s lymphoma, which is a cancer of the immune system, rather than a cancer of the breast tissue.  It occurs in the scar tissue and the fluid surrounding the implant within the breast capsule, but can also spread throughout the body. 

The most recent data available suggests that BIA-ALCL most often occurs among patients with textured breast implants, as the surface of the implant provides space for bacteria to attach and proliferate.      

 

FDA Reports

On March 21 2017, the FDA reported that the exact number of cases of BIA-ALCL has been difficult to determine "due to significant limitations in world-wide reporting and lack of global implant sales data." 

Despite the limitations, the FDA released updated information on the number of reported cases earlier today.  In this March 2018 news report, they state the following:

As of September 30, 2017, the FDA had received a total of 414 medical device reports (MDRs) of BIA-ALCL, including the death of nine patients.

272 of the 414 reports included information on the surface information of the implant at the time of the report, including 242 with textured surfaces and 30 with smooth surfaces...In the MDR reports, half of the reported cases were diagnosed within 7-8 years of implantation.

This data was last updated in September 2017.  

 

Ongoing Investigation

In the report released earlier today, the FDA provided the following information on their efforts:

[W]e are working to update and enhance the information we have on this association, including updating the total number of known cases of BIA-ALCL and the lifetime risk of developing BIA-ALCL as reported in medical literature.

We hope that this information prompts providers and patients to have important, informed conversations about breast implants and the risk of BIA-ALCL.  At the same time, we remain committed to working in partnership with all stakeholders to continue to study, understand and provide updates about this important public health issue.

Going forward, we will continue to monitor the medical and regulatory information for updates on the number of reported BIA-ALCL cases and the condition's association with breast implants.

In the meantime, we encourage you to visit our website for more information and submit a free case evaluation if you or someone you know has been diagnosed with BIA-ALCL.

 

Breast Implants: Lymphoma / Blood Cancer Cases Overview

Free Breast Implants Case Evaluation

---

Previous articles on this topic:

• New Data Released on Risk of Lymphoma Due to Breast Implants
• Breast Implant-Associated Lymphoma Diagnoses on the Rise
• What is the Risk of Death Due to Breast Implant-Associated Lymphoma?
• Breast Implants and Lymphoma: Who's to Blame?
• Breast Implant Lymphoma: Causes Uncertain, but Costs Undeniable
• Breast Implants Linked to Rare Lymphoma Blood Cancer

 

Breast Implants: Lymphoma / Blood Cancer Cases Overview

Free Breast Implants Case Evaluation

---

Previous articles on this topic:

• New Data Released on Risk of Lymphoma Due to Breast Implants
• Breast Implant-Associated Lymphoma Diagnoses on the Rise
• What is the Risk of Death Due to Breast Implant-Associated Lymphoma?
• Breast Implants and Lymphoma: Who's to Blame?
• Breast Implant Lymphoma: Causes Uncertain, but Costs Undeniable
• Breast Implants Linked to Rare Lymphoma Blood Cancer

Gout Medicine Uloric May Require Recall or Increased Warnings of Cardiac Death

 

Written by: Heather Helmendach, Legal Assistant 
Law Offices of Thomas J. Lamb, P.A.

 

About Uloric

Uloric (febuxostat) is indicated for the chronic management of hyperuricemia in patients with gout.  Gout is a form of arthritis, and occurs when uric acid in the body builds up and causes sudden attacks of redness, swelling, and pain in one or more joints.  

Uloric is considered a xanthine oxidase (XO) inhibitor, and eases gout symptoms by lowering uric acid levels in the blood.

 

Prior Warnings

When Uloric was approved by the US Food and Drug Administration (FDA) in 2009, its manufacturer, Takeda Pharmaceuticals, was required to conduct a safety study.  The study was titled "Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Comorbidities" (CARES).  This trial recently concluded, but the FDA has yet to complete their comprehensive review of the study results.

On November 15 2017, the FDA issued a drug safety communication concerning Uloric based on the preliminary findings of the study.  In this document, they warned of an increased risk of heart-related death with Uloric compared to other gout medications that contain allopurinol.

In addition, they provide the following information:

The primary outcome was a combination of heart-related death, non-deadly heart attack, non-deadly stroke, and a condition of inadequate blood supply to the heart requiring urgent surgery. The preliminary results show that overall, febuxostat did not increase the risk of these combined events compared to allopurinol. However, when the outcomes were evaluated separately, febuxostat showed an increased risk of heart-related deaths and death from all causes.

At this stage, the mechanism of harm is not clearly understood.  Otherwise put, researchers are unsure how exactly Uloric is causing death in patients who use it.

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Drug Label

The current drug label for Uloric warns that when compared to similar gout drugs that contain allopurinol, Uloric has a higher rate of cardiovascular thromboembolic events such as cardiovascular deaths, non-fatal myocardial infarctions, and non-fatal strokes.  However, they are quick to point out that no causal relationship has yet been established. 

Going forward, the FDA is considering adding increased warnings to the drug label for Uloric in order to more adequately convey the risk of cardiac-related deaths.  According to a recent MedScape article, "Options include a new warning in the labeling in addition to the one already there, or pulling [Uloric (febuxostat)] from the market."  The article also mentions several doctors who are not in favor of removing Uloric from the market, given its advantages over allopurinol in certain populations.

We will continue to monitor the medical and regulatory literature for more information on the association between Uloric and fatal cardiovascular events, and report on significant developments.

 

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Increased Reports of Intraocular Inflammation due to Eylea Injections

 

Written by: Heather Helmendach, Legal Assistant 
Law Offices of Thomas J. Lamb, P.A.

 

About Eylea

Eylea is an eye injection that is indicated for the treatment of the following diseases of the retina:

• Neovascular (Wet) Age-Related Macular Degeneration (AMD)
• Macular Edema Following Retinal Vein Occlusion (RVO)
• Diabetic Macular Edema (DME)
• Diabetic Retinopathy (DR) in Patients with DME

Regeneron Pharmaceuticals is responsible for manufacturing Eylea, which was approved by the FDA in 2011.

 

Increase in Side Effects

Over the past several months, an increased number of patients who receive Eylea injections have experienced sharp declines in vision, pain, and even vision loss.  These symptoms were attributed to intraocular inflammation (IOI), which is a known side effect of Eylea and similar drugs.

According to a Bloomberg article from February 21, 2018, the "FDA received 71 reports last year" out of the 2.2 million vials of Eylea that were distributed, which was "almost triple 2014 when [one million vials were distributed and] the next-highest number were made."

While the total number of reported incidents remains low, the American Society of Retina Specialists (ASRS) felt that the situation warranted a letter to its members.  They maintained that the benefits of Eylea far outweigh the reported risks, but that doctors should still be aware of the unexplained increased potential for the IOI side effect.

The manufacturer launched an internal investigation to ascertain the cause of this spike in adverse events in late February.

 

Assumed Cause

Regeneron released the following information in a February 28, 2018 letter they sent to healthcare providers:

We did not identify any association of IOI rates with the Eylea drug itself, but an association was seen with certain batches of the syringe included in specific lots of final packaged Eylea kits.

While Regeneron was quick to point the finger at the manufacturer of the syringes included in their Eylea kits--Becton, Dickinson & Company--no specific flaw or contamination of the syringes was discussed.

They did however provide eight lot numbers of Eylea kits that contained "affected syringes," and advised doctors not to use the syringes provided in those lots.

Lastly, they stated that they will provide a more detailed report of their findings in an "upcoming scientific meeting."

We will continue to monitor the medical news concerning Eylea and the spike in incidences of IOI, and report on significant developments as we become aware of them.

 

 

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Gadolinium-Based Contrast Agents: Timeline of FDA Regulatory Actions

 

Written by: Heather Helmendach, Legal Assistant 
Law Offices of Thomas J. Lamb, P.A.

 

In my last article on Gadolinium based contrast agents (GBCAs), I discussed some of the side effects of these injections, which are administered to patients during a Magnetic Resonance Imaging (MRI) or Magnetic Resonance Angiography (MRA).

While GBCAs have started to draw attention in the pharmaceutical products liability legal realm, they have been the subject of several drug safety regulatory actions here and abroad over the past 12 years.

The timeline below provides dates and descriptions of the regulatory actions pertaining to GBCAs, based on information from the US Food and Drug Administration (FDA).

 

Timeline of Regulatory Action for GBCAs

2006	The FDA released a Public Health Advisory announcing their investigation of nephrogenic systemic fibrosis (NSF) as a result of GBCA exposure in patients with some degree of kidney failure.  A report of 25 cases of NSF served as a catalyst for the FDA's investigation.
2007	The FDA added a “black box warning” to the drug labels of GBCAs, advising those with renal insufficiency to avoid GBCAs given the increased risk for NSF.
2010	The FDA made a Safety Announcement that they were "requiring changes in the drug label for gadolinium-based contrast agents (GBCAs) to minimize the risk of nephrogenic systemic fibrosis (NSF), a rare, but serious, condition associated with the use of GBCAs in certain patients with kidney dysfunction."
2015	The FDA issued a Drug Safety Communication stating that "Recent publications in the medical literature have reported that deposits of GBCAs remain in the brains of some patients who undergo four or more contrast MRI scans, long after the last administration."
May 2017	The FDA issued a Drug Safety Communication announcing that they have "not identified adverse health effects from gadolinium retained in the brain after the use of gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI)." They also reported that various scientific "publications and [adverse event] reports show that gadolinium is retained in organs such as the brain, bones, and skin. The publications show that linear GBCAs retain more gadolinium in the brain than macrocyclic GBCAs. However, the review did not identify adverse health effects related to this brain retention." The European Medicines Agency (EMA), however, recommended a ban on the use of Linear GBCAs based on the results of their Pharmacovigilance and Risk Assessment Committee's (PRAC) assessment.  They also state that "Although no symptoms or diseases linked to gadolinium in the brain have been reported, the PRAC took a precautionary approach, noting that data on the long-term effects in the brain are limited."
Dec. 2017	The FDA issued a Drug Safety Communication announcing that they are "requiring a new class warning and other safety measures for all gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI) concerning gadolinium remaining in patients’ bodies, including the brain, for months to years after receiving these drugs."
2018	The FDA released new drug labels for GBCAs, which include more information on gadolinium retention.

 

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Looking Ahead

Lawsuits are already emerging for conditions such as Gadolinium Deposition Disease (GDD), which are caused by retention of gadolinium in the brain, bones, and other organs.

While the FDA has warned that gadolinium retention is possible after receiving GBCAs, they claim that they have yet to find any evidence that such retention causes serious adverse events in patients with normal / adequate renal function.

It will be interesting to see if further research and publications in the medical literature will cause the FDA to change their position on this issue.

We will continue to monitor the medical and regulatory literature concerning the risk of GDD as a result of GBCA use during MRI and MRA procedures, and report on any significant developments.

 

 

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Gadolinium Deposition Disease can Result from use of Contrast Agents During MRI & MRA Procedures

 

Written by: Heather Helmendach, Legal Assistant 
Law Offices of Thomas J. Lamb, P.A.

 

What are Gadolinium-Based Contrast Agents (GBCAs)?

GBCAs are substances that are injected into patients during Magnetic Resonance Imaging (MRI) or Magnetic Resonance Angiography (MRA) in order to produce clearer radiology images.

Here is a list of GBCAs that are currently approved by the FDA:

• Ablavar
• Dotarem
• Eovist
• Gadavist
• Magnevist
• MultiHance
• Omniscan
• OptiMARK
• ProHance

These substances contain gadolinium, a toxic synthetic heavy metal, which is bonded to a linear or macrocyclic compound in order to reduce toxicity. 

While the bonding compounds are designed to help usher gadolinium out of the body, sometimes the bonds break and gadolinium is left behind in the bones, brain, and various tissues within the body.

 

What can happen when Gadolinium remains in the body?

Several conditions can occur as a result of gadolinium retention:

• Nephrogenic systemic fibrosis (NSF)
• Gadolinium storage condition
• Gadolinium deposition disease

NSF occurs in patients with renal insufficiency.  In these patients, gadolinium cannot be removed from the body adequately as a result of decreased kidney function.  As a result, thickening and darkening of the skin, shortening of the muscles and tendons, and other symptoms can occur.  This condition can potentially be fatal.

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Gadolinium storage condition is the excess of gadolinium in patients with normal renal function. 

Gadolinium deposition disease occurs when a patient has an excess of gadolinium in their system, but they have normal or adequate renal function. Symptoms of this condition can manifest anywhere from a few hours to several weeks after the GBCA injection was administered, and are as follows:

• Persistent headache
• Severe pain in the bones, joints, arms, and legs
• Sensation of sharp pins and needles, cutting, or burning
• Cognitive impairment
• Clouded mentation (“brain fog”)
• Nausea / vomiting
• Thickening of soft-tissue, tendons, and ligaments
• Tightness in the hands and feet

 

What actions are being taken?

Regulatory agencies here and abroad have taken steps to warn patients about the potential for gadolinium retention as a result of GBCA use.

In my next article, I will further discuss the specific regulatory actions that have occurred over the years.  I will also discuss the current status of this situation in the U.S. as well as in Europe.

Rest assured that we will continue to monitor the medical literature concerning the risk of NSF and gadolinium deposition disease as a result of GBCA use during MRI and MRA procedures, and report on any significant developments.

 

 

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Uterine Fibroid Drug Esmya Investigated Due to Severe Liver Injuries

 

Written by: Heather Helmendach, Legal Assistant 
Law Offices of Thomas J. Lamb, P.A.

 

About Esmya

Esmya (ulipristal acetate) is indicated for the treatment of severe symptoms caused by uterine fibroids -- or noncancerous growths in the uterus -- in women of reproductive age.

While Esmya is currently available in Europe, it is still pending FDA approval in the U.S. 

The active ingredient, ulipristal acetate is the same as that of Ella, an emergency birth control medication that is approved in the U.S.  However, a key difference between the two medications is the dose amount and frequency.  While Ella is a 30mg tablet meant to be used once, Esmya is a 5mg tablet to be used once daily for treatment courses of up to 3 months each.

 

Reports of Severe Liver Injury

The European Drug Label for Esmya lists "Hepatic impairment" in the "Special warnings and precautions for use" section. 

Here is an alarming excerpt from this section:

During the post-marketing experience, cases of liver injury and hepatic failure were reported.  During treatment, liver function tests should be performed at least monthly. In addition liver testing 2- 4 weeks after treatment has stopped is recommended. If a patient shows signs or symptoms compatible with liver injury (nausea, vomiting, right hypochondrial pain, anorexia, asthenia, jaundice, etc.), the patient should be investigated immediately, and liver function tests performed.

Four cases of severe liver injuries in patients using the drug have already been reported to the European Medicines Agency (EMA), three of which resulted in liver transplants.

 

Ongoing Investigation

In December 2017, the EMA's Pharmacovigilance Risk Assessment Committee (PRAC) began their investigation of the association between Esmya and liver failure.  

They provide the following information in their investigation announcement letter:

EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has made an initial assessment of the cases of liver injury and considered that Esmya could be the cause.

Given the seriousness of the observed liver injury and its possible link to the medicine, a more in depth review is warranted.

While the investigation is still underway, the EMA has advised healthcare providers to refrain from initiating treatment with Esmya.  They also encouraged doctors to closely monitor the liver function of patients already taking the drug to see if stopping treatment is necessary.

We will continue to monitor the medical literature here and abroad for developments in the PRAC's investigation of Esmya, and report accordingly.

 

 

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MiraLax Pediatric Study on Psychiatric Side Effects Projected to be Completed in 2018

 

Written by: Heather Helmendach, Legal Assistant 
Law Offices of Thomas J. Lamb, P.A.

 

Issue

While MiraLax (polyethylene glycol 3350) is typically intended for use in patients 17 years of age and older, it has apparently been prescribed "off-label" for many years to children for constipation relief.

What's worse is that MiraLax is typically prescribed for a maximum of seven days to adults, but some children were taking it for much longer periods of time in order to treat chronic constipation.

Thousands of parents whose children were prescribed MiraLax observed deeply troubling neuropsychiatric problems in their children after using MiraLax such as:

• Depression
• Anger
• Anxiety
• Paranoia
• Mood swings

In fact, a "Citizen Petition to Investigate Polyethylene Glycol 3350 Product Safety for Use with Pediatric Patients" was filed back in 2012 urging the FDA to add a "black box" warning to its label pertaining to neuropsychiatric side effects in children.  They also requested information concerning all clinical trials and studies done on polyethylene glycol (PEG) 3350, and demanded that the FDA conduct additional studies on its effects in children.

 

FDA's Response

2006	The FDA deferred submission of studies concerning the effects of MiraLax on the pediatric population (those 16 years of age or younger) until October 2016. While they required the manufacturer, Bayer, to submit annual reports on the progress of the pediatric studies, it is unclear whether they have submitted such reports.
2008	Eight batches of MiraLax were tested by the FDA for impurities.  According to an FDA spokesperson, this action was in response to the numerous adverse event reports they received, in which patients exhibited “classic symptoms of ethylene glycol ingestion.”   In all eight tested batches, the FDA found traces of ethylene glycol (EG) and diethylene glycol (DEG), which are ingredients found in antifreeze.
2011	The FDA reported that neuropsychiatric events were observed in users of MiraLax, but stated that "no action is necessary at this time based on available information."
2013	When the agency conducted further tests of laxatives containing PEG 3350, the amounts of EG and DEG were reportedly so low that they were classified as "acceptable."
2014	The FDA agreed to fund a study on MiraLax and other products containing PEG 3350, as requested in the 2012 Citizen Petition.  This study would be conducted by the Children's Hospital of Philadelphia (CHOP), and was to begin some time in 2014.   The title of the study is, "The Use of Polyethylene Glycol in the Pediatric Population," and it is classified as a research project.
2017	The following information is provided on the status of the CHOP study: (see full text of 11/29/17 email) CHOP must develop assays for the relevant PEG 3350 metabolites and lower molecular weight polyethylene glycols of interest before it can complete the remaining study activities and analyze the results... Once the assays development is concluded, the testing phase should proceed relatively quickly, as obtaining the required samples should be fairly straightforward...  CHOP has indicated that it will be able to complete the remaining study activities and analysis in 2018.

 

 

Current Events

A decade after the safety of MiraLax and other PEG 3350 laxatives was first questioned, the FDA reports that the CHOP study should be completed by the end of 2018.

However, parents are not optimistic about the results of the study based on the eight studies that have already been conducted.  These studies are mentioned in the Polyethylene Laxatives Fact sheet from CHOP, and all state that "no behavioral problems were reported."  Although, a key difference between these previous studies and the current CHOP study is that the CHOP study is directly studying behavioral changes in children, while the past studies did not.

As of December 31, 2017, 709 cases of "psychiatric disorders" have been reported to the FDA according to the FDA Adverse Events Reporting System (FAERS) Public Dashboard.  Of note, 344 of these reported cases occurred in 2017, most likely due to the increased media attention surrounding the MiraLax safety debate.

While we await the results of the CHOP study on the safety of PEG 3350 products in children, we will continue to monitor the medical and regulatory news for significant developments.

 

 

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Limbrel Medical Food Product for Osteoarthritis Removed from the Market

 

Written by: Heather Helmendach, Legal Assistant 
Law Offices of Thomas J. Lamb, P.A.

 

Background

Limbrel (flavocoxid) is an anti-inflammatory agent comprised mostly of flavonoids such as baicalin and catechin that is prescribed to manage the metabolic processes associated with osteoarthritis.

This supplement has traditionally been classified and marketed as a "medical food," which is defined by the Orphan Drug Act as:

"a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation."

Recently, Limbrel has been under fire by the FDA due to its alleged misclassification as a "medical food," as well as the increasing number of adverse side effects that have been reported by users of Limbrel.

 

Limbrel Side Effects

While a range of reactions have been reported to the FDA by users of Limbrel, the most serious and potentially life-threatening ones are as follows:

• Drug-induced liver injury
• Pancreatitis
• Hypersensitivity pneumonitis (inflammation of the alveoli within the lung)

While drug-induced liver injury and hypersensitivity pneumonitis (HP) were previously mentioned on the FDA's website page about Limbrel, the pancreatitis side effect was more recently discussed in the FDA Requested Recall letter, mentioned in the following section of this article.

HP in particular can be difficult to diagnose, given that the symptoms -- such as fever, chills, fatigue, cough, chest tightness, difficulty breathing, and headache -- are common to other, less serious conditions.  Clinical, radiological, physiological, and immunological tests are often needed in order to properly diagnose this condition.

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Of note, the package insert for Limbrel (accessed 1/12/18) does warn that there have been "rare" cases of HP observed in those taking Limbrel, but brushes the warning aside saying that those who experienced this side effect eventually "recovered uneventfully and without residua."  

They also warn of "rare cases of severe hepatic reactions accompanied by jaundice or eosinophilia," in a casual manner, stating that "all of these cases resolved within 2-4 weeks without residua after LIMBREL was discontinued."

To clarify, the manufacturers probably used the word "residua" in these warnings to mean "residual effects."  Going forward, they had better hope that their legal teams pay more attention to semantics when defending their classification of Limbrel as a "medical food" against the FDA.

 

 

Trouble with the FDA

The FDA disagrees with Limbrel's classification as a medical food, and has argued that it is actually a "new drug" that has not been approved by the FDA "on the basis of scientific data and information demonstrating that the drug is safe and effective."  As such, the FDA urged consumers to immediately stop taking Limbrel, and the manufacturer, Primus Pharmaceuticals, to voluntarily recall it.

In November 2017, the FDA initially contacted Primus in regard to the numerous reports of potentially life-threatening side effects of Limbrel observed by consumers and medical professionals.  Several weeks later, they reiterated their concerns related to these possible side effects and recommended a voluntary recall.

Primus initially refused to comply, prompting a "Requested Recall" letter from the FDA in mid-December 2017, which stated:

This letter is to request that you cease distribution and immediately initiate a recall of all lots within expiry of the following products:

- Limbrel (flavocoxid) 250 mg capsules
- Limbrel250 (250 mg flavocoxid with 50 mg citrated zinc bisglycinate) capsules
- Limbrel (flavocoxid) 500 mg capsules
- Limbrel500 (500 mg flavocoxid with 50 mg citrated zinc bisglycinate) capsules

As of earlier this month, Primus has finally agreed to comply with the FDA's request to cease the promotion and sale of Limbrel. 

They have criticized the FDA at every step, however, claiming that they have received "unwarranted pressure" from the FDA, who has issued "repeated aggressive press releases" urging them to withdraw Limbrel from the market in spite of "the major public health implications."

We will monitor the medical and legal news for updates on this situation, and report any significant developments as we become aware of them.

 

 

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