Troglitazone (Rezulin)
Since 1993 we have interviewed over 5000
potential clients in the areas of breast
implant, Fen-Phen, asbestosis, silicosis, and
other injury and medical-device related
actions. Since the withdrawal of Rezulin from
the market by the FDA, we have begun to
provide information to Rezulin users at no
cost. We are happy to provide you that same
information, or to discuss and review your
individual situation with you. The references
shown below will lead you to some of the
critical information you need in this fast
breaking area. The source of this information
includes the FDA, the drug manufacturer
itself, and various medical and legal
information sources. After completing your
review, you can contact us by (1) calling us
toll free at 800-447-6443, or (2) contacting
us by E-mail.
- Brand name:
Rezulin (US),
Noscal (Japan)
- Class:
thiazolidinedione
- Route of Administration:
oral
- Dose:
200 mg with a meal; if
no improvement within a few weeks, can
increase to 400 mg with a meal (and later
to 600 mg).
- Previously available as
:
200 mg, 300 mg, and 400 mg
tablets.
- Previously recommended by FDA for:
Type 2 diabetes, in combination with
sulfonylurea pills, or combination with
both sulfonylurea pills and metformin (see
Diabetes Monitor Re: metformin),
or with insulin injections.
- Action
: improves the action
of the liver, muscles, and fat tissues
(functions as an "insulin sensitizer")
- Side Effects:
Fluid
retention, increased fertility, liver
disease (see
Diabetes Monitor).
|
|
Contact your doctor if you experience
any of the following within the first
few months of starting Rezulin, even if
your most recent liver enzyme test was
normal: |
|
Nausea |
|
Abdominal pain |
|
Vomiting |
|
Dark urine |
|
Fatigue |
|
Loss of appetite |
|
Jaundice (yellowed skin) |
|
|
|
-
US manufacturer: Parke-Davis division of Warner-Lambert.
Developed by Sankyo Pharm. Company in
Japan.
- Status:
Voluntarily withdrawn by the
manufacturer March 21, 2000 in the
USA. Suspended in the U.K. in Dec.
1997 pending review of safety data and
later withdrawn from the UK market.
|
A
letter to Physicians
A
letter to Pharmacists
|
· Other drugs in same class:
pioglitazone,
rosiglitazone
· Sources of
Information: Clinical Diabetes,
July-August, 1995; New England Journal
of Medicine, Volume 331, pages 1188 -
1227, 11/3/94, product insert, information
from Parke-Davis, and press stories (see
Diabetes Monitor).
|
|
#
# #
Rezulin
Info from RxList.com
Note:
FDA removed from the US market 3/21/00
###
The
following is the text of a Press Release
issued by the manufacturer on March 21,
2000:
(See
http://www.warner-lambert.com/press/release.asp?release=109).
MORRIS
PLAINS, N.J., March 21, 2000 --
Warner-Lambert Company announced today
that it is voluntarily discontinuing the
sale of REZULIN (troglitazone) Tablets,
its therapy for the treatment of type 2
diabetes, although the Company continues
to believe that the benefits of the drug
outweigh its associated risks.
Patients
taking REZULIN should consult with their
physicians as soon as possible to discuss
alternative therapies. Warner-Lambert will
work closely with the Food and Drug
Administration and other constituencies to
assure a safe and efficient transition for
patients as they switch to alternative
therapies.
The
Company has always believed that it is
essential for patients and physicians to
receive accurate and objective information
regarding the benefits and risks of
REZULIN. It was for this reason that
Warner-Lambert requested a public meeting
of the FDA’s expert Advisory Committee.
However, repeated media reports
sensationalizing the risks associated with
REZULIN therapy have created an
environment in which patients and
physicians are simply unable to make
well-informed decisions regarding the
safety and efficacy of REZULIN. Under
these circumstances, and after discussions
this evening with the FDA, we have decided
it is in the best interests of patients to
discontinue marketing REZULIN at this
time.
# # #
In
June, 1999, the FDA and Parke-Davis agreed
to again tighten the restrictions on the
use of troglitazone
-
The
previous indication for use as
monotherapy (by itself) was withdrawn.
-
Liver
testing (ALT) was recommended monthly
for a year, then quarterly
-
If
ALT's increase to 1.5-2.0 the upper
limits of the normal range, they should
be repeated immediately and weekly; if
the patient develops jaundice or ALT
over 3.0 times the upper limits of
normal, the drug should be discontinued
-
It
was recommended that patients with the
following not be started on
troglitazone:
-
Patients
with ALT over 1.5 times the upper
limit of the normal range
-
Patients
with prior liver disease
-
Patients
with active liver disease
-
Patients
with alcohol abuse
#
# #
Parke-Davis
Announcements July 28, 1998
In
a letter addressed to Healthcare Professionals
July 28, 1998, Parke-Davis made two
announcements.
-
A
revised warning about testing for liver
abnormalities (see
Diabetes Monitor):
"...in consultation with the FDA,
[P-D] has modified the prescribing
information in the following way:
-
Patients
with moderately elevated ALT levels at
the start of therapy (greater than 1.5
times the upper limit of normal) should
not be initiated on Rezulin therapy.
-
ALT
levels should be measured at the start
of Rezulin therapy and monthly for eight
months, then every two months for the
remainder of the first year of therapy
and periodically thereafter.
-
Patients
whose ALT levels are found to be
moderately elevated (greater than 1.5-2
times the upper limit of normal) during
Rezulin therapy should have ALT levels
retested within a week and then weekly
until they either return to normal
levels or rise above 3 times the upper
limit of normal, at which point Rezulin
should be discontinued."
-
Note:
In June, 1999, the indication for
monotherapy with troglitazone was
withdrawn.
In the same letter, P-D advised modifications
to monotherapy prescribing information:
"The recommendation for use as
initial therapy has been modified to the
following:
-
For
patients not responding to 400 mg, the
Rezulin dose should be increased to
600 mg after one month
[emphasis in original].
-
For
patients not responding adequately to
600 mg after one month
[emphasis in original], Rezulin should
be discontinued and alternative
therapeutic options should be
pursued."
|
# # #
|
Tuesday
December 2 2:11 AM EST
FDA Strengthens Warnings for Diabetes
Drug
WASHINGTON
(Reuters) - Doctors should carefully
monitor patients who are taking
Rezulin, a new diabetes drug, for
signs of liver damage, the U.S. Food
and Drug Administration (FDA) said
Monday (see
Diabetes Monitor).
It
strengthened its recommendations about
the drug, known generically as
troglitazone, after reports that some
people on the drug had suffered liver
failure and three had died.
"FDA
has concluded that liver enzyme levels
should be measured in patients taking
Rezulin at the start of therapy, every
month for the first six months of
treatment, every other month for the
next six months, and periodically
thereafter," the FDA said in a
statement.
Information
about possible liver damage should be
more prominently displayed on the
label of the drug, made by Parke-Davis,
a unit of Warner-Lambert Co, the FDA
said.
"These
actions, taken with the full
cooperation of the drug's
manufacturer, re-emphasize for health
care providers and patients the
importance of monitoring patients
taking Rezulin to ensure that it is
used in the safest manner," the
FDA said.
The
FDA said about 600,000 patients in the
United States and 200,000 in Japan had
taken Rezulin which is prescribed with
insulin or olde drugs known as
sulfonylureas for patients whose blood
sugar levels are not being controlled
by the other treatment.
The
FDA announced the danger of liver
damage on November 3, after getting
reports of 35 cases of liver damage,
including liver failure that caused
one liver transplant and killed
another person.
"At
that time the FDA asked for reports on
additional adverse events associated with
the use of Rezulin, and the agency has
received a total of approximately 150
adverse event reports, including three
deaths fron liver failure linked to the
use of Rezulin in Japan," it said.
About
two percent of patients taking the drug
show an elevation of certain liver enzymes
in the blood, a possible indication of
liver damage.
"Although
FDA will carefully monitor and evaluate
reports of liver problems associated with
Rezulin, at present the agency continues
to find the benefits outweigh the risks
for treating appropriately selected and
monitored type-2 diabetes patients with
Rezulin," it said.
Warner
shares fell sharply after the company said
it would be changing the labels on the
drugs.
Concern
was magnified when Glaxo Wellcome Plc,
which manufactures and markets the drug in
the United Kingdom under the name Romozin,
said earlier on Monday it was suspending
sales of the drug pending its review of
safety data.
Glaxo
also announced it had withdrawn its
license applications under the European
Commission's mutual recognition process to
sell the drug in other European countries. |
# # #
Asscoiated Press, U.S. News,
Houston Chronicle of March 25,
2000 reported:
Tension Around FDA Drug Approval
By PHIL GALEWITZ
AP Business Writer
FDA
Commissioner David Kessler
AP/Dennis Cook
NEW
YORK (AP) — The government's system
for approving drugs is coming under
renewed scrutiny after a number of
widely used medicines have been linked
to deaths or serious illness.
Critics
say the Food and Drug Administration
moves too quickly and puts the drug
industry's interests ahead of patient
safety. As evidence they point to seven
drugs that have been pulled from the
market or severely restricted in the
past three years. This week alone the
diabetes drug Rezulin and the heartburn
drug Propulsid were added to the list.
``The
FDA is acting in a reckless way to make
sure they are not alienating the
industry,'' said Sidney Wolfe, director
of the Public Citizen Health Research
Group and frequent critic of the agency.
FDA
officials insist their system works, but
they stress all the side effects of
drugs cannot be known until after a drug
is approved, and is taken by tens of
thousands of patients. Typically, drugs
are only tested on about 3,000 people
before getting approved.
``There
is no truth to the idea that we are any
easier on drug approvals,'' said Dr.
Robert Temple, FDA's associate director
for medial policy.
The
FDA acknowledges there has been a spate
of recalls, but says that when viewed
over the course of several years, the
percentage of drugs pulled from the
market has remained stable.
A
spokesman for the drug industry agreed.
Since
1980, there have been 528 medicines
approved and only 12 or 2 percent have
been recalled because of safety reasons,
said the Pharmaceutical Research and
Manufactures of America. ``The fact that
only 2 percent have been withdrawn shows
two things: The benefits of marketed
drugs outweigh the risks, and the safety
system in place is working,'' said
spokesman Jeff Trewhitt.
The
FDA accelerated its drug review process
during the 1990s after Congress
complained it was taking too long to
approve life-saving medicines.
In
the 1980s it usually took almost three
years for the agency to approve a drug.
Today, the average approval time is one
year. For drugs the FDA deem
breakthrough medicines, it knocks the
review time down to six months.
The
acceleration process was shepherded by
then FDA commissioner David Kessler, who
now wonders about how far it's gone.
``We
have to be mindful that the pendulum has
not swung too far,'' Kessler said
Friday.
As
drug recalls have made headlines in
recent years, Congress has begun to pay
closer attention to whether the FDA is
doing its job properly.
In
January, a study the General Accounting
Office, Congress' investigative arm,
concluded the FDA lacks the ability to
properly track problems with drugs after
they hit the market. The office
recommended that pharmacists work more
closely with doctors in prescribing and
monitoring drugs.
Part
of the problem might be related to the
drug industry's increased use of
consumer advertising, which is spurring
more sales of newer drugs. Rapid
introduction of new drugs means that
doctors have less experience with them
before they are taken by millions of
people.
``We
tend to want to see the upside of
pharmaceuticals and tend to forget they
all have risks, something we see with
the drugs that have been withdrawn,''
Kessler said.
Wolfe
said the FDA has been too reluctant to
take drugs off the market once it
discovers problems. He said the agency
is too reliant on adding warning labels
to the drugs — a system that can fail
if doctors fail to read them.
Warner-Lambert's
Rezulin was approved in 1997 after just
six months of government review because
regulators deemed it a crucial new
therapy. But within a year the drug was
linked to serious liver problems and
deaths. The FDA placed several
restrictions on the drug last year, and
on Tuesday the agency decided to ban it
altogether.
One
key factor in the FDA's decision to ban
the drug now was the fact that two
alternatives were approved last year,
Avandia and Actos.
The
FDA also tried to use warning labels to
when it discovered problems with Johnson
& Johnson's Propulsid. It changed
the labeling five times since the drug
was approved in 1993 as it learned about
new situations when the drug could cause
illness or death. On Thursday, with
prodding from the FDA, the company said
it would stop marketing the drug which
had $950 million in sales in 1999 and it
would stop distributing it to drug
stores in July… |
FDA
TALK
PAPER
Food
and
Drug
Administration
U.S.
Department
of
Health
and
Human
Services
Public
Health
Service
5600
Fishers
Lane
Rockville,
MD
20857
--------------------------------------------------------------------------------
FDA
Talk
Papers
are
prepared
by
the
Press
Office
to
guide
FDA
personnel
in
responding
with
consistency
and
accuracy
to
questions
from
the
public
on
subjects
of
current
interest.
Talk
Papers
are
subject
to
change
as
more
information
becomes
available.
--------------------------------------------------------------------------------
T97-61
Marian
Segal:
301-827-6242
December
1,
1997
Broadcast
Media:
301-827-3434
Consumer
Hotline:
800-532-4440
PATIENT
TESTING
AND
LABELING
STRENGTHENED
FOR
REZULIN
The
U.S.
Food
and
Drug
Administration
today
announced
that
patients
taking
the
diabetes
drug
Rezulin
(troglitazone)
should
be
monitored
more
frequently
for
signs
of
injury
to
the
liver.
In
addition,
warning
information
about
potential
liver
toxicity
will
be
more
prominently
featured
in
the
drug's
labeling.
These
actions,
taken
with
the
full
cooperation
of
the
drug's
manufacturer,
re-emphasize
for
health
care
providers
and
patients
the
importance
of
monitoring
patients
taking
Rezulin
to
ensure
that
it
is
used
in
the
safest
manner.
Rezulin
is
used
in
combination
with
insulin
or
sulfonylurea
in
patients
with
type
II
diabetes
(adult-onset
diabetes
mellitus)
whose
blood
glucose
levels
are
not
adequately
controlled
by
these
other
therapies
alone.
On
November
3,
FDA
and
the
drug's
manufacturer
announced
changes
in
the
prescribing
information
for
Rezulin,
including
a
new
warning
and
recommendations
for
monitoring
liver
function.
In
making
these
changes,
FDA
was
aware
of
approximately
35
post-marketing
reports
of
liver
injury
among
U.S.
and
Japanese
patients
taking
Rezulin,
including
liver
failure
leading
to
one
liver
transplant
and
one
death.
At
that
time,
FDA
asked
for
reports
on
additional
adverse
events
associated
with
the
use
of
Rezulin,
and
the
agency
has
now
received
a
total
of
approximately
150
adverse
event
reports,
including
three
deaths
from
liver
failure
linked
to
the
use
of
Rezulin
in
Japan.
Approximately
600,000
patients
in
the
U.S.
and
200,000
in
Japan
have
been
treated
with
this
drug.
The
deaths
in
Japan
occurred
in
patients
treated
before
the
stronger
label
warning
and
recommendation
for
liver
enzyme
testing
took
effect
there.
FDA
has
concluded
that
liver
enzyme
levels
should
be
measured
in
patients
taking
Rezulin
at
the
start
of
therapy,
every
month
for
the
first
six
months
of
treatment,
every
other
month
for
the
next
six
months,
and
periodically
thereafter.
In
addition,
liver
function
tests
should
be
performed
on
any
patient
on
Rezulin
who
develops
symptoms
of
liver
dysfunction,
such
as
nausea,
vomiting,
fatigue,
loss
of
appetite,
or
dark
urine
and
jaundice.
The
product's
current
labeling
advises
that
patients
with
significant
elevation
of
these
liver
enzymes
stop
taking
the
drug.
Previously,
liver
enzyme
testing
was
recommended
during
the
first
two
months
of
therapy
and
then
every
three
months.
The
increased
monitoring
of
patients
taking
Rezulin
is
designed
to
detect
those
few
patients
in
whom
use
of
the
drug
can
lead
to
serious
liver
damage.
Warner-Lambert,
the
manufacturer
of
the
drug,
will
send
a
letter
within
the
next
week
to
U.S.
health
care
professionals
to
inform
them
of
these
changes.
While
Rezulin
was
being
studied
in
patients
before
FDA
approval,
approximately
two
percent
of
all
patients
were
found
to
develop
elevation
of
liver
enzymes
in
the
blood.
These
elevations,
which
serve
as
markers
of
potential
liver
injury,
were
mostly
mild,
unassociated
with
symptoms,
and
usually
resolved
when
the
drug
was
discontinued.
Although
FDA
will
carefully
monitor
and
evaluate
reports
of
liver
problems
associated
with
Rezulin,
at
present
the
agency
continues
to
find
the
benefits
outweigh
the
risks
for
treating
appropriately
selected
and
monitored
type-2
diabetes
patients
with
Rezulin.
Type
2
diabetes
is
a
serious,
life-threatening
disease
that
affects
18
million
Americans.
It
is
a
leading
cause
of
coronary
heart
disease,
blindness,
kidney
failure,
and
limb
amputation.
Adequate
control
of
blood
sugar
appears
to
be
the
most
important
means
of
preventing
these
complications.
#
#
#
On
November
3,
1997,
the
FDA
issued
the
following
warning
about
troglitazone:
Rezulin
Labeling
Changes
The
manufacturer
of
the
diabetes
drug
Rezulin
(troglitazone)
is
changing
prescribing
information
for
the
product
and
adding
new
warning
information
to
the
labeling,
in
response
to
reports
of
liver
injury
associated
with
use
of
the
drug.
Rezulin
is
used
in
combination
with
insulin
or
sulfonylurea
in
patients
with
type
II
diabetes
(adult-onset
diabetes
mellitus)
whose
blood
glucose
levels
are
not
adequately
controlled
by
these
other
therapies
alone.
About
500,000
patients
in
the
United
States
have
been
treated
with
Rezulin
since
it
came
on
the
market
in
January
1997;
of
those,
approximately
85,000
have
been
taking
the
drug
for
six
months
or
more.
As
of
|
