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(DIR) Return to: TECFIDERA (dimethyl fumarate, BG-12, Fumaderm)
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#Post#: 569--------------------------------------------------
FDA warns of PML risk with Tecfidera in MS
By: agate Date: November 26, 2014, 6:22 pm
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From Medscape, November 25, 2014:
[quote]FDA Warns of PML Risk With Tecfidera in MS
Susan Jeffrey
The US Food and Drug Administration (FDA) issued a warning today
about a fatal case of progressive multifocal leukoencephalopathy
(PML) in a patient treated for multiple sclerosis (MS) with
dimethyl fumarate (Tecfidera, Biogen Idec).
"The patient who died was not taking any other drugs that affect
the immune system or drugs that are thought to be associated
with PML," a drug safety communication from the FDA states. "As
a result, information describing this case of PML is being added
to the Tecfidera drug label."
The European Medicines Agency's Pharmacovigilance Risk
Assessment Committee released a statement November 7 advising
physicians to inform patients about this fatal case of PML, the
first such case reported in association with this new oral
agent. PML is a well-known risk associated with natalizumab
treatment (Tysabri, Biogen Idec).
"The drug manufacturer, Biogen Idec, notified FDA when the MS
patient died after developing PML. The patient had taken
Tecfidera for more than four years," the FDA safety
communication says.
"Prior to developing PML, the patient had a very low number of
lymphocytes, a type of white blood cell, in her blood. Reduced
lymphocyte counts can weaken the immune system, which increases
the risk for PML," it adds. "It is unknown whether the low
lymphocyte count contributed to the development of PML in this
patient, or if low lymphocyte counts are a risk factor for PML
development in Tecfidera-treated patients."
The FDA safety communication recommends that health
professionals should:
~Tell patients taking Tecfidera to contact them if they develop
any symptoms that may be suggestive of PML. "Symptoms of PML are
diverse, progress over days to weeks, and include the following:
progressive weakness on one side of the body or clumsiness of
limbs; disturbance of vision; and changes in thinking, memory
and orientation, leading to confusion and personality changes,"
the statement notes. "The progression of deficits can lead to
severe disability or death."
~Stop treatment immediately at the first sign or symptom
suggestive of PML and perform an appropriate diagnostic
evaluation.
~Monitor lymphocyte counts in Tecfidera-treated patients
according to approved labeling.
Healthcare professionals and patients are encouraged to report
adverse events or side effects related to the use of these
products to MedWatch, the FDA's safety information and adverse
event reporting program, by telephone at 1-800-FDA-1088; by fax
at 1-800-FDA-0178; online at
(HTM) https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm
(HTM) https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm;<br
/>with postage-paid FDA form 3500, available at
(HTM) http://www.fda.gov/MedWatch/getforms.htm
(HTM) http://www.fda.gov/MedWatch/getforms.htm;
or by mail to
MedWatch, 5600 Fishers Lane, Rockville, Maryland 20852-9787....
[/quote]
The article can be seen here
(HTM) http://www.medscape.com/viewarticle/835437#vp_1.
#Post#: 597--------------------------------------------------
Re: FDA warns of PML risk with Tecfidera in MS
By: agate Date: December 25, 2014, 7:56 pm
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More information on this case is in this article in Doctor's
Guide, December 23, 2014:
[quote]FDA Warns About Case of PML With MS Drug Dimethyl
Fumarate
ROCKVILLE, Md -- November 25, 2014 -- The US Food and Drug
Administration (FDA) is warning that a patient with multiple
sclerosis (MS) who was being treated with dimethyl fumarate
(Tecfidera) developed progressive multifocal leukoencephalopathy
(PML) and later died.
The patient who died was not taking any other drugs that affect
the immune system or drugs that are thought to be associated
with PML. This is the only confirmed case of this rare and
serious brain infection reported in patients taking dimethyl
fumarate.
As a result, information describing this case of PML is being
added to the drug’s label.
The drug manufacturer, Biogen Idec, notified the FDA when the
patient died after developing PML. The patient had taken
dimethyl fumarate for more than 4 years. Prior to developing
PML, the patient had a very low number of lymphocytes in her
blood. It is unknown whether the low lymphocyte count
contributed to the development of PML in this patient, or if low
lymphocyte counts are a risk factor for PML development in
dimethyl fumarate -treated patients.
We urge health care professionals and patients to report side
effects involving dimethyl fumarate to the FDA MedWatch program,
using the information in the “Contact FDA” box at the bottom of
the page.
Healthcare professionals should:
•
develop any symptoms that may be suggestive of PML. Symptoms of
PML are diverse, progress over days to weeks, and include the
following: progressive weakness on one side of the body or
clumsiness of limbs; disturbance of vision; and changes in
thinking, memory and orientation, leading to confusion and
personality changes.
•
symptom suggestive of PML and perform an appropriate diagnostic
evaluation.
•
according to approved labelling.
Data Summary
A 54-year-old patient with MS being treated with dimethyl
fumarate in a clinical trial died after developing PML. The
patient, who had an 18 year history of MS, had no known medical
conditions that would predispose her to the development of PML.
She had no history of prior use of immunosuppressive medications
and was not taking any concomitant immunosuppressive or
immunomodulatory medications.
She had taken glatiramer acetate (Copaxone) for 3 years prior to
being enrolled in a dimethyl fumarate clinical trial. In the
clinical trial, she had received placebo for 2 years followed by
dimethyl fumarate for approximately 4.5 years prior to
developing PML. During dimethyl fumarate treatment, she had
severe lymphopenia, with lymphocyte counts consistently below
500 cells/mcL for 3.5 years before developing PML.
Two months prior to her death, the patient was hospitalised with
a presumed MS relapse and treated with corticosteroids. Her
condition continued to worsen, and dimethyl fumarate was stopped
at that time. A diagnostic evaluation suggested PML, and this
diagnosis was confirmed when tests identified John Cunningham
(JC) viral DNA in the cerebrospinal fluid. The patient developed
aspiration pneumonia due to dysphagia and died approximately 7
weeks after discontinuation of dimethyl fumarate.
PML has previously been reported in Europe in patients treated
with other drugs containing dimethyl fumarate. The FDA was aware
of 4 PML cases at the time of dimethyl fumarate approval in
2013. Three cases occurred in patients with psoriasis who took a
combination product sold in Germany that includes dimethyl
fumarate and 3 different salts of monomethyl fumarate, and 1
case in a patient treated with a compounded product that
included dimethyl fumarate. In 2 of these cases, the patients
had previous exposure to immunosuppressive therapy. In the other
2 cases, patients had prolonged lymphopenia with documented
lymphocyte counts below 500 cells/mcL. The contribution of
dimethyl fumarate to the development of PML in these cases is
unknown.
Healthcare professionals and patients are encouraged to report
adverse events or side effects related to the use of these
products to the FDA's MedWatch Safety Information and Adverse
Event Reporting Program:[/quote]
The article can be seen here
(HTM) http://www.docguide.com/fda-warns-about-case-pml-ms-drug-dimethyl-fumarate?hash=544098a8&eid=42618&alrhash=2e22ec-4b70c95432d7b63d98dcc4c365f92710.
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