More harmful than NOSCAL that have
been banned already!!!
Not only heart failure! If Myocardial Infarction occurs,
it may be irreversible!!
We concluded in February 1998 that Troglitazone
(NOSCAL in Japan and REZULINE in the US) should be
And it was finally withdrawn from the US market and
subsequently withdrawn also from the Japanese market in March 2000. It was
too late but of course an inevitable measure. However where have gone the
interest which they earn by selling almost 200 million US dollars in Japan
and 700 million US dollars in the US?. Who our cost for insurance would cover? How about the compensation for the
victims who suffered from the adverse reaction to Noscal
Troglitazone have been withdrawn, but we become
anxious about the safety of ACTOS that was approved in November 1999 and
might be used increasingly instead of Noscal
So NPOJIP precisely analyzed the data of ACTOS used
for the approval. It was found that ACTOS might be as harmful as Noscal
What will happen when a patient
with heart disease become swelled?
What do you think will happen when a patient with
heart disease become swelled?
A patient with heart failure is already swelled. It
may be very easy for you to imagine that he or she will be easily become
worse even if you were not healthcare professionals.
Swelling is a phenomenon in which water is
increased outside blood vessels. When water is increased outside blood
vessels, water inside of the blood vessels is also increased. A patient
with heart failure who has weakened heart cannot circulate blood well and
a lot of blood is stay in vein, which causes retention of a lot of water
all over the body.
patient swelled more, more water and more blood stay in the body and the
heart failure may easily worsen. As one among eight women taking ACTOS
become swelled, so they have high risks to become heart failure. Moreover,
patient with heart arrhythmia may worsen, and patients with heart attack
in the past may experience a new attack again.
does not work below the dose that causes toxicity
Such a product
is not a drug, nothing but a toxin
ACTOS was shown to lower blood sugar in rats with
artificially induced diabetes mellitus. It is claimed in the colorful
But the beneficial effects of ACTOS are not shown
below 3 mg/kg/day in rats (3 mg per kg body weight every day). This is the
same dose that can produce an effective level (actually, area under the
curve: AUC) of active ingredients in human. But almost the same dose (3.6
mg/kg/day by mouth) for one year have shown to induce harm effect on the
heart and/or bone in the animals. It means that the beneficial effects can
be sown first at the dose that harms the animal.
Harmful effects to heart are more serious than to
seems less toxic to the liver than Noscal (Rezuline). In the animal
toxicity tests, liver toxicity is not so strong. The heart and not
the liver is the organ in which toxicity appear at first.
cardiomyopathy and lung bleeding
mg/kg/day by mouth of ACTOS (the equivalent to the clinical dose
for human) induced hypertrophy (enlargement) of the heart, abnormal
bone forming and decrease of bone weight (compatible with osteoporosis
in human). Higher dose (14.5 mg/kg/day) induced cardiomyopathy with
scattered focal necrosis of heart muscles and lung bleeding which
may be related to the heart failure.
These abnormalities (cardiomyopathy
and lung bleeding) did not recovered after four month stopping ACTOS.
It means those abnormalities are irreversible. Mortality increased
related to the dose increased.
Cardiotoxicity is apparent at the
human clinical dose
lowest effective dose in the animal that is compatible with human
clinical dose is definitely harmful to the heart. This dose or more
for one year induced cancer in the urinary bladder. So ACTOS may
So it is substantially probable that diabetic
patients treated with ACTOS for many years will have heart disease,
fragile bone and/or cancer even if they have no other diseases
Heart failure and/or Myocardial
infarction were actually reported
In the clinical trial of ACTOS, rate with anemia,
elevation of LDH (indicating cell damage somewhere in the body), CPK
(indicating muscle damage), ALT/AST (indicating liver damage) were almost
same or higher than that by Noscal (Rezuline). Overall frequency of
swelling (edema) was 7 %, but 13 % of women treated with ACTOS experienced
swelling (edema)Swelling (edema) is harmful for diabetic patients. Heart
failure and/or Myocardial infarction were reported from abroad and in
patients tend to have heart complications. Heart diseases are one of the
most important complication which diabetes patients wants to prevent. So
the agent that induce heart disease or cancer as the first abnormality
should be disqualified as a drug for the treatment of diabetes
use ACTOS! It should be banned
Emergency letter for the safety
we have been warning that it should be banned, emergency doctor
letter in which ACTOS should not be administered to the patients
with heart failure have been issued on 5th October 2000, since five
patients have been reported to get heart failure or the heart failure
become worse. It will be easy to understand for you from our explanations
that problem is not only for heart failure.
final endpoints of the management of diabetes mellitus are to prevent
complications in cardiovascular system, kidney and retina (eye) and to
prolong comfortable life. But ACTOS will almost definitely increase heart
diseases including heart failure, myocardial infarction (heart attack)
and/or cardiac arrhythmia. Heart complications are observed frequently not
only in the animal study but also in the clinical trials. For example,
among patients who were treated with ACTOS for more than half a year, only
one myocardial infarction was reported as those classified as severe heart
diseases. However among the heart diseases classified as moderate heart
diseases, one was revealed actually as myocardial infarction, eight were
increased heart-lung ratio (this means almost heart failure), three were
abnormal echocardiogram, one had difficult breath on exercise, one had
moderate pounding heart, seven had abnormal electrocardiogram including
atrial fibrillation (a sort of cardiac arrhythmia), totally 22 patients
had any moderate or severe heart complications among 321 patients-year:
this means 6.8 patients among 100 patients treated with ACTOS will get
moderate or severe heart diseases within one
surveyed clinical trials of ACTOS and of other drugs for diabetes
mellitus. We selected placebo groups of clinical trials of ACTOS and
experimental group as well as control group of clinical trials for other
drugs for diabetes mellitus as control of ACTOS. Only one myocardial
infarction, two patients with asthma or breath difficulty, totally tree
was the moderate or severe complication with these treatment for 599
person-year, i.e. 0.6 per 100 person per year. These shows that ACTOS much
more easy to induce heart disease (it is expressed as p=5.45×10-8 ).
than heart was 2.8 per 100 per year for both ACTOS and for control (3.0
for Noscal) with no difference. However if you combine ACTOS and Noscal
(Rezuline), incidence of cancer is significantly higher and that of peptic
ulcer is tend to be higher for them than for others.
comparisons are not the results obtained by randomized controlled trials
(drawing-lots-trials), they are merely one of the information. But in the
animal studies, lowest effective dose enlarged heart and reduced bone
weight, dose of four times dose of lowest effective dose have induced
cardiomyopathy with necrosis of heart muscle and lung bleeding both of
that did not recover. Above that dose, mortality increased. So,
considering together with the results of the animal toxicity studies,
ACTOS should be considered as more dangerous especially for heart.
Japan Institute of
Pharmacovigilance (JIP) has requested the Minister of Health and Welfare
to withdraw ACTOS immediately from the market on the 6th October 2000.
Subsequently, NPOJIP, TIP and Med Watcher Japan (Yakugai Ombudspersons
Committee) as well requested that ACTOS should be banned and should be
recalled. on 10th October
taking ACTOS abruptly will never harm the patients under
the diabetes get worse after stopping ACTOS, insulin may perhaps
be necessary for her or for him.
Noscal (or Rezuline or troglitazone) was
withdrawn from the market but the license has never revoked. ACTOS should
be withdrawn from the market and the license of Noscal and ACTOS should be
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