Drug Injury Watch

Lymphoma Cancer Associated With Breast Implants: FDA Advisory Committee Meeting March 2019

Warning Letters Sent To Companies Mentor Worldwide And Sientra For Breast Implants Safety Monitoring Failures

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

Albeit a bit off-topic for the general focus of this Drug Injury Watch blog, we have been monitoring and writing about Breast Implant Associated Anaplastic Large-Cell Lymphoma (BIA-ALCL) for the past two years. Over that time period, the FDA has become more and more interested in this lymphoma cancer "side effect", if you will, as well as other breast implant safety issues. This increased concern is now culminating in a two-day meeting of medical experts to be convened next week.

Specifically, there will be an FDA CDRH General and Plastic Surgery Devices Advisory Committee Meeting held on March 25-26, 2019. As the FDA Agenda document for this meeting shows, the first day will be focused in large part on the lymphoma cancer associated with breast implants, ALCL, which is a rare type of blood cancer that is classified as a non-Hodgkin lymphoma, and one of the sub-types of T-cell lymphoma.

As is customary for FDA Advisory Committee Meetings, background materials and specific panel questions were released by the FDA prior to the March 25-26, 2019 breast implants meeting. Those items are set forth below:

• Meeting Information for the Public: March 25-26, 2019 (PDF - 53KB)
• Agenda: March 25, 2019 (PDF - 145KB)
• Agenda: March 26, 2019 (PDF - 118KB)
• FDA Executive Summary: March 25-26, 2019 (PDF - 848KB)
• FDA Executive Summary Appendix: March 25-26, 2019 (PDF - 70KB)
• Panel Questions: March 25-26, 2019 (PDF - 71KB)
• Roster: March 25-26, 2019 (PDF - 50KB)

From the FDA Executive Summary document, titled "Breast Implant Special Topics", we get this focal point:

Breast implants are associated with BIA-ALCL, a cancer of the immune system. While most patients with BIA-ALCL may be treated only with breast implant removal, some patients have required radiation therapy, chemotherapy or both, and some patients have died from BIA-ALCL.  [See "Introduction", at page 5]

A more detailed discussion of Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) can be found at pages 13-18 of this FDA Executive Summary document.

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Moving onto a different aspect of the breast implant safety topic, on March 19, 2019 there appeared this FDA News Release, "FDA issues warning letters to two breast implant manufacturers for failure to comply with post-approval study requirements".

This excerpt comes from the start of that March 2019 FDA document:

Today, the U.S. Food and Drug Administration issued warning letters to two breast implant manufacturers for failure to comply with their requirements, under their premarket approval orders, to conduct post-approval studies to assess the long-term safety and risks of their silicone gel-filled breast implants.

The FDA issued warning letters to Mentor Worldwide LLC of Irvine, California, and Sientra, Inc. of Santa Barbara, California. Every manufacturer of approved silicone gel-filled breast implants is required to conduct post-approval studies to further evaluate safety and effectiveness of the products and to answer additional scientific questions about the long-term safety and potential risks of breast implants that their premarket clinical trials were not designed to answer.

For those who want to know more, you can read one or both of the FDA warning letters to those breast implant manufacturers:

• Letter to Mentor Worldwide LLC & Acclarent 3/18/19
  
  
• Letter to Sientra Inc 3/18/19

As our law firm has been actively investigating BIA-ALCL cases for women as possible lawsuits against these companies and other breast implant manufacturers, we applaud the increased scrutiny that the FDA is bringing to the breast implant safety issue.

If you want to learn more about this issue, you can start at our Breast Implants Lymphoma Cancer information page.

 

Gadolinium Contrast Agents Side Effects: Medical Literature Review, September 2018 - February 2019

Researchers Continue To Investigate Gadolinium Deposition Disease (GDD) Following Gadolinium-Based Contrast Agents Injections

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

In recent years it has been recognized that the gadolinium contained in certain contrast agents can break away from its bonding agent.  As a result, gadolinium is left behind in the bones, brain, and various tissues within the body. In turn, when this happens, there might be gadolinium side effects.

Specifically, this situation can lead to Gadolinium Deposition Disease (GDD) in patients, which is a form of gadolinium toxicity and sometimes called, instead, Gadolinium Storage Condition.

Medical researchers continue to investigate the extent and severity of gadolinium retention following injections of gadolinium-based contrast agents for MRIs, MRAs, and CT scans.

Presented below is a collection of medical articles published in the past six months -- September 2018 to March 2019 -- about this still developing safety issue for contrast agents containing gadolinium.

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Safety of Gadolinium Administration in Children

Pediatric Neurology medical journal (September 2018 edition) -- Abstract

The introduction of paramagnetic contrast in the late 1980s constituted a paradigm shift boosting the efficacy of magnetic resonance imaging. Due to its high magnetic moment, gadolinium-based contrast agent made its way smoothly as the flagship paramagnetic contrast. With the widespread application, reports of untoward effects started to surface. Allergic reactions, nephrogenic systemic sclerosis, and deposition in brain tissue dented the safety profile of gadolinium-based contrast agent. Better understanding of these adverse effects prompted preventive measures. This article elucidates the gadolinium-based contrast agent toxicity in the pediatric population based on the current available evidence.

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How widespread is gadolinium accumulation in the brain?

AuntMinnie.com news report (October 31, 2018) -- Preview of November 28, 2018 scientific sessions at the annual RSNA show

Gadolinium accumulation in the brain may occur with both linear and macrocyclic contrast agents, and it could be more widespread than previously thought, according to researchers from Switzerland....

The researchers found that repeated administration of a gadolinium-based contrast agent (GBCA) was associated with increased overall signal intensity for both linear GBCAs and macrocyclic GBCAs. However, the most interesting findings were the locations of heightened signal intensity and the apparent causes.

The researchers found significant signal intensity increases in the dentate nucleus and globus pallidus after linear GBCA administration but not macrocyclic GBCA use. Conversely, they observed significant signal increases in the thalamus, putamen, amygdala, caudate, hippocampus, and accumbens from macrocyclic GBCAs but not linear GBCAs.

"Based on our findings, gadolinium accumulation in the brain may be more widespread than assumed and could occur with the use of both linear and macrocyclic GBCAs," the researchers concluded.

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Long-term Excretion of Gadolinium-based Contrast Agents: Linear versus Macrocyclic Agents in an Experimental Rat Model

Radiology medical journal (Published Online: November 13, 2018) -- Abstract

Purpose:  To investigate the long-term course of MRI signal intensity (SI) changes and the presence of gadolinium in the rat brain during a 1-year period after multiple administrations of gadolinium-based contrast agents (GBCAs).

Conclusion:  Increased signal intensity in the deep cerebellar nuclei of rats persists for at least 1 year after administration of linear gadolinium-based contrast agents (GBCAs), in line with persistent brain gadolinium concentrations with no elimination after the initial 5-week period. The animals that received macrocyclic GBCAs showed an ongoing elimination of gadolinium from the brain during the entire observation period.

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Gadolinium retention in gliomas and adjacent normal brain tissue: association with tumor contrast enhancement and linear/macrocyclic agents

Neuroradiology medical journal (First Online: February 2, 2019) -- Abstract

Purpose:  To quantitate gadolinium deposits in gliomas and adjacent normal brain specimens, and to evaluate their association with tumor contrast enhancement and the type of gadolinium-based contrast agent (GBCA) used.

Conclusion:  Gadolinium can be detected in both enhancing and non-enhancing gliomas, neighboring normal brain, and necrosis. Gadolinium retention is higher after exposure to linear GBCAs compared with the macrocyclic gadoterate meglumine.

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Be assured that we will continue to monitor the medical literature for developments related to gadolinium retention in connection with our investigation of cases of Gadolinium Deposition Disease (GDD) in patients who received injections of gadolinium based contrast agents for their MRI, MRA, or CT scan procedure.

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

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review done by attorney Tom Lamb)

Uloric "Black-Box Warning" For Increased Risks Of Heart-Related Deaths And Cardiovascular Side Effects

February 2019: Despite Safety Trial Finding A Link To Cardiac Deaths, FDA Does Not Order Uloric Recall At This Time

 

(Posted by Tom Lamb at DrugInjuryWatch.com)

 

This new article about the gout drug Uloric (febuxostat) is an update for one we posted about six weeks ago, "Uloric Recall, 'Black-Box Warning', And Limited Use Discussed By FDA Advisory Committees In January 2019".

We start with an overview taken from a February 21, 2019 MedPage Today report, "FDA: Gout Drug Raises Death Risk":

The FDA concluded its months-long investigation into mortality risk with [Uloric (febuxostat)] by mandating strong warnings on the product label and restricting use.

Approved use is now only after maximally titrated [Zyloprim (allopurinol)] fails or isn't tolerated.

[Uloric (febuxostat)] will have to carry a black-box warning of increased risk of cardiovascular and all-cause mortality compared with [Zyloprim (allopurinol)], as had been shown in the CARES trial, and update the patient medication guide with that information.

FDA also recommended that clinicians monitor for cardiovascular signs and symptoms for patients on [Uloric (febuxostat)].

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For more detailed information, we go to the Data Summary part of this February 2019 FDA Drug Safety Communication, "FDA adds Boxed Warning for increased risk of death with gout medicine Uloric (febuxostat)":

When FDA approved Uloric (febuxostat) in 2009, we included in the prescribing information a Warning and Precaution regarding possible cardiovascular events in patients treated with Uloric. We also required the drug manufacturer, Takeda Pharmaceuticals, to conduct a large postmarket clinical trial to evaluate the cardiovascular safety of Uloric.... The primary endpoint was a composite of major adverse cardiovascular events (MACE): cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and unstable angina with urgent revascularization. Secondary endpoints included the individual components of the MACE composite as well as death from any cause. The study... [found] there was a significant increase in cardiovascular death....

This recent clinical trial finding was the basis for the FDA set forth in the Safety Announcement part of that FDA document:

The U.S. Food and Drug Administration (FDA) has concluded there is an increased risk of death with Uloric (febuxostat) compared to another gout medicine, allopurinol. This conclusion is based on our in-depth review of results from a safety clinical trial that found an increased risk of heart-related death and death from all causes with Uloric.

As a result, we are updating the Uloric prescribing information to require a Boxed Warning, our most prominent warning, and a new patient Medication Guide. We are also limiting the approved use of Uloric to certain patients who are not treated effectively or experience severe side effects with allopurinol.

In summary, while there was no Uloric recall ordered, the FDA required its strongest safety warning, i.e., Bolded Warning or Black-Box Warning, for the Uloric drug label to inform about the increased risk of heart-related death and death from all causes with Uloric.

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

Drug Injury Case Evaluation - Free. Confidential. No Obligation.  (Case review done by attorney Tom Lamb)