Actos® and Bladder CancerRecent
studies have shown that patients taking the drug Actos for longer than
one year may suffer significantly increased risks of developing bladder
cancer. The FDA warnings are being issued on the heels of France and
Germany banning the use of Actos, and New Zealand also beginning the
process of removing Actos from patient use. Takeda Pharmaceuticals, the
Japanese corporation who began manufacturing Actos in 1999, is at the
midway point in a ten-year study of the drug’s potentially serious side
effects. While the five-year data shows no clear evidence of an overall
increased risk of bladder cancer, patients who have taken the drug in
the highest dosages or for the longest period of time appeared to be at a
much greater risk of developing bladder cancer. Actos
is in a class of drugs known as thiazolidinediones, and is the second
medication of its class to be associated with serious side effects.
Avandia, the sister-drug of Actos, recently had its use severely
restricted due to evidence of increased heart attack risk and even
death. When metformin alone no longer works well for patients suffering
from type 2 diabetes, doctors typically prescribe a drug such as Actos
which increases the body’s insulin sensitivity, controlling blood sugar
levels in the process. Type 2 diabetes, when left untreated, can
potentially lead to serious health effects such as damage to the retina
which can lead to blindness, injury to the kidneys, impairment of the
nerves which could lead to amputations of limbs and an acceleration of
the development of fat plaques on the interior of the arteries which can
potentially lead to blood clots, blockages, cardiovascular disease,
stroke and a lessening of critical circulation.
Actos® and Congestive Heart FailureThe
drug Actos, also known as pioglitazone is marketed by Takeda
Pharmaceuticals and Eli Lilly for the treatment of Type 2 diabetes. The
drug was approved in 1999, and although the manufacturer touts it as a
miracle drug which has reduced the number of diabetes cases by as much
as 70%, the side effects may far outweigh the benefits. A study done in
2003 by the Mayo Clinic definitively linked Actos to swelling in the
feet, lung fluid retention, shortness of breath and congestive heart
failure. The most recent studies have strongly indicated that Actos may
also be responsible for a number of incidences of bladder cancer in
those who have taken the drug in higher dosages or for longer than
twelve months. The American
Diabetes Association presented a research report at a meeting in San
Diego this past June which reported that Actos enhanced the risk of
macular edema by as much as six times, causing thickening and swelling
of the retina and leading to blindness. Another study which was reported
in the American Heart Association Journal in August, 2010, associated
Actos with an increased risk of death due to congestive heart failure.
Although the FDA had mandated a black box warning for Actos regarding
possible heart failure risks in 2007, the warnings became even more
stringent this past June.
Actos® Damages and Typical Settlements
The
Type 2 diabetes drug Actos is one of a class of drugs known as
thiazolidinediones and has recently been linked to an increased risk of
bladder cancer, liver disease and cardiovascular issues. The FDA felt
that the link between heart failure and Actos was serious enough to
require increased warnings on the drug packaging concerning congestive
heart failure. According to the Washington Post on 8/05/11, the first
of what is expected to be literally thousands of lawsuits was filed
alleging the use of Actos resulted in bladder cancer. Takeda
Pharmaceuticals, a Japanese corporation is the manufacturer of Actos
although it was jointly launched with the American company, Eli Lilly.
Actos quickly became a top-seller of the giant pharmaceutical
corporations, becoming the tenth best-selling drug in the United States
in 2008 with sales over 2.5 billion dollars increasing to a staggering
4.3 billion in 2010.
In June of
2011, Takeda halted its sales of Actos in both France and Germany after
receiving considerable pressure from health regulators in both those
countries. New Zealand is currently in the process of pulling the drug
as well. Since June, both the FDA and the European Medicines Agency have
prudently issued warnings regarding the potential risk of bladder
cancer for those taking the drug, but are allowing the continuation of
sales pending further studies. The FDA has, however, warned doctors not
to prescribe the drug for those who have a history of bladder cancer or
who currently have bladder cancer.
Actos® FDA Safety Review/Warning
On
June 15, 2011, the United States Food and Drug Administration informed
the public that using the drug Actos, commonly prescribed in the
treatment of Type 2 diabetes, has been positively associated with an
increased risk of bladder cancer. Actos is manufactured by a Japanese
pharmaceutical company, Takeda Pharmaceuticals, and is typically sold
either as a single-ingredient product or in combination with the drug
metformin. Actos is prescribed, along with diet and exercise, to help
control blood sugar in adults. Initially the FDA’s safety warnings were
based on a five-year interim analysis of an ongoing ten year study
regarding the risks for those taking Actos.
While
the study at the five-year mark noted an increased risk of bladder
cancer among those who had taken Actos in the highest dosages and for
the longest periods of time, it was unclear about the overall increased
bladder cancer risk. Two other countries, France and Germany, have taken
more definitive actions regarding Actos, believing it poses serious
health risks. While France has suspended the use of Actos altogether,
Germany has recommended to physicians that they not start new patients
on the drug. New Zealand is currently in the midst of recalling the
drug, yet the FDA continues to maintain that further study is warranted
before issuing more stringent warnings.
Actos® Side Effects other than Heart Disease and Bladder Cancer
Osteoporosis and Bone Fractures
While
many people are now aware of the association between the Type 2
diabetes drug, Actos, and both bladder cancer and heart disease, there
are several other quite serious side effects also associated with the
drug. For instance, there is strong evidence to suggest that Actos, like
its sister-drug, Avandai, may cause osteoporosis and bone fractures
among those taking it, most especially in female patients. In one
particular randomized trial which studied patients with Type 2 diabetes
who were currently taking Actos, an increased occurrence of bone
fractures was observed in the female patients and in a follow-up study
at nearly three years, almost 5.1% of the females taking Actos had
suffered a bone fracture.
Most
of the bone fractures were seen in arms and legs, and there was no
apparent escalation of fracture occurences among male patients. Because
this drug study lasted less than five years, it is strongly believed
that a much greater frequency of fractures and osteoporosis would be
seen in women taking Actos for longer periods of time. Since men
typically have much stronger bones than women, fractures and
osteoporosis would probably not have been seen in men who were studied
for only a few years. Since broken hipbones happen to be a primary
killer of the elderly, seniors should not take Avandia or Actos as their
benefits do not appear to outweigh the serious side effects.
Actos® Adverse EffectsMany of us would be very surprised to find that a drug can be approved by the FDA yet still have serious—and undisclosed—side effects. The drug Actos, used in the treatment of Type 2 diabetes, is one such drug. Actos works by decreasing the body’s resistance to insulin as a way of controlling blood sugar levels. Actos is currently being used by millions of people across the globe, with sales jumping from around $2.9 billion in 2006 to over $4.3 billion in 2010. Actos has often been prescribed in place of the drug Avandia, which was found to carry significant risks of heart disease and possibly even death in 2007. Actos, which is manufactured by the Japanese pharmaceutical giant Takeda Pharmaceuticals, has recently fallen under scrutiny as well as studies have linked it to an increased risk of bladder cancer as well as correlating it to other serious diseases such as heart attack, stroke and liver failure. “Minor” Side Effects of ActosThe truth is, all prescription medicines as well as most over-the-counter medications, carry some risk of adverse effects. Fortunately the incidence of serious side effects is rare and for the most part the majority of people have either no side effects or relatively minor ones. Minor side effects associated with Actos include flu-like symptoms, headaches, toothache, sore throat or sinus pain and weight gain. More serious side effects which should prompt the user to seek medical attention include an allergic reaction which includes difficulty breathing or chest tightness, blurry vision, symptoms of heart or liver failure including breathing difficulties, a sudden gain in weight, stomach pains, dark urine, jaundice or vomiting, low blood sugar symptoms such as tremors, anxiety or chills, severe and unusual bone pain and total exhaustion along with feeling weak and shaky.
Actos® and Cardiovascular DangersThe drug Actos, marketed by Takeda Pharmaceutical Corporation, is used in the treatment of Type 2 diabetes. Actos largely replaced its predecessor, Avandia, after Avandia was found to have serious risks of heart attack and heart failure. At the time, it was believed that Actos offered much less risk of cardiovascular damage than Avandia. Actos is used to lessen blood glucose labels and improves how the body handles insulin. Type 2 diabetes, which affects between eighteen and twenty million Americans, can cause loss of sight, kidney trouble and cardiovascular illness if left untreated, however it appears that the treatment may also come with its fair share of serious dangers. Just like Avandia, Actos may carry significant levels of cardiovascular risks, however it has not been associated with heart attack deaths in the same way Avandia has. Although Takeda is in the middle of a ten-year study regarding the safety of Actos, other studies have been conducted as well. One well-known cardiologist, Dr. Steven Nissen of the Clevenland clinic focused his review of Actos dangers, finding that it significantly increases the likelihood of a heart attack by as much as forty-two percent. The FDA issued a black box warning label for Actos in June of 2007 during a House of Representatives hearing. During this hearing the fact that the FDA was aware of the potential cardiovascular risks associated with Actos yet failed to adequately respond was discussed, and since that time both lawmakers and health experts have criticized the FDA for failing to properly safeguard public health.
Actos® and Myocardial InfarctionAfter a Journal of American Medical Association publication of a meta-analysis suggested that long-term use of the diabetes drug Avandia was associated with an increased risk of myocardial infarction, the maker of Avandia, GlaxoSmithKline, declared there was little difference in the safety profile of their drug, Avandia and the “other” drug for Type 2 diabetes, Takeda Pharmaceutical’s Actos. Further studies however have not completely backed up that declaration. In nineteen separate controlled trials, involving over 16,000 patients, the end results demonstrated that while 4.4 percent of the patients who received Actos underwent myocardial infarction or stroke 5.7 percent of patients receiving control therapy suffered a myocardial infarction. In the same studies, serious heart failure was reported in 2.3 percent of those taking Actos, while only occurring in 1.8 percent of those in the control group. The author of the results of the studies, Michael Lincoff, stated that not only does Actos—also known as pioglitazone—not appear to have the same level of detrimental effects as Avandia, but it could potentially have a protective effect on the heart. Takeda Pharmaceuticals, currently struggling under the rash of lawsuits filed against them due to evidence that Actos may significantly increase the risk of bladder cancer, does not believe their drug is responsible for episodes of myocardial infarction, or heart attack.
Actos® European Recall and FDA StanceA wave of recent studies which definitively link the prescription drug Actos—prescribed for Type 2 diabetes—to bladder cancer gives a fairly clear indication that Takeda Pharmaceuticals may soon be flooded with Actos lawsuits. August, 2011, saw the first Actos lawsuit filed by a 54-year old woman from Pennsylvania who had taken Actos for over a decade, then was diagnosed with bladder cancer. It is likely this particular victim may end up having her bladder removed and be subject to chemotherapy treatments due to the unexpected and severe side effects of Actos. Although the FDA has made substantial changes in labeling for Actos, they have refused to go as far out on the limb as other countries who have issued recalls of the drug. France’s Medical Regulatory Agency made the decision to recall Actos once the serious side effects became known. Some 230,000 people regularly take Actos in France, and the possibility of an increase in bladder cancer was felt to be too great to allow patients to continue to take the drug. Soon after, Germany’s health regulators advised physicians to stop prescribing Actos for their patients with Type 2 diabetes due to the potentially dangerous side effects of the drug. These recalls and prohibitions were made after the European Medicines Agency conducted its own study of drugs which contained pioglitazone.
FDA Approves Cancer Warning for Diabetic Drug ActosThe
blockbuster drug, Actos, which is prescribed to control Type 2
diabetes, has received new warning language on the label regarding a
potential risk of bladder cancer for those taking the drug. Actos, also
known as pioglitazone, is manufactured by Takeda Pharmaceuticals, a
Japanese-based company, and is currently their best-selling drug, with
sales of $3.4 billion last year alone. Sales of Actos had shown a
significant upswing due to the fact that its primary
competitor—Avandia—has been linked to a higher risk of heart attack and
even death. The updated label warnings came on the heels of an EMA
safety review of the drug as well as a ten-year study conducted by
Takeda. The Takeda study indicated a statistically significant increase
in the risk of bladder cancer for those taking the drug for longer than
two years. Other Drugs Containing PioglitazoneOther
than Actos, the drugs ActoPlus Met, ActoPlus Met XR and Duetact will
all carry the same warnings due to containing pioglitazone as an active
ingredient. All of these drugs are used to treat Type 2 diabetes, to
increase sensitivity to insulin and effectively control blood sugar
levels. A combination drug containing metformin and pioglitazone is used
for the same purpose, although all these drugs are expected to be used
in conjunction with a healthy diet and sensible exercise program. France and Germany Weigh InJust
this past June, both France and Germany issued recalls of Actos
following a public insurance data review which showed a fairly strong
correlation between pioglitazone and bladder cancer risk. Suggestions
from the EMA study related primarily to including more cautionary
warnings on the labels of the drug as well as a six-month review of each
patient taking Actos.
Pioglitazone Receives New Warnings Due to Slight Increase in Bladder Cancer RiskThe
health review of the Type 2 diabetic drug, pioglitazone, performed by
the European Medicines Agency, confirmed the drug remains a valid
treatment option for certain patients while acknowledging a minimal
increase in bladder cancer risk. The caveat in the conclusions of the
health review centered upon advising physicians to use care and caution
when prescribing the drug. The results further stated that those who are
prescribed pioglitazone—especially those who take relatively high doses
or have taken the drug for longer than a year—must have their overall
health monitored closely. Exclusion of certain higher risk groups, such
as the elderly is also recommended. Assessing Risk Factors in Potential PatientsPhysicians
are warned to screen patients carefully, and avoid prescribing
pioglitazone to those who have a history of bladder cancer or who
currently have bladder cancer. Patients with uninvestigated macroscopic
haematuria are also advised against taking pioglitazone. As stated, age
carries a specific risk, as the elderly are already more likely to
develop bladder cancer based solely on age. Because of this an
alternative diabetes medication with less risk in this area should be
prescribed. Patients taking Actos should undergo regular 3-6 month
reviews to assess and monitor benefit vs. risk. Sources of InformationIn
making its safety recommendations, the Committee for Medicinal Products
for Human Use considered results of pre-clinical and clinical studies
as well as spontaneous reports and epidemiological studies. The
Scientific Advisory Group on Diabetes also weighed in with advice
regarding pioglitazone. The CHMP concluded from this array of evidence
that while there is a slight increase in bladder cancer among those
taking pioglitazone, this risk exists primarily in those who take the drug for long periods of time or in relatively high doses. That being
said, those who take the drug for a short amount of time cannot be
excluded from the risks.
Takeda Pharmaceuticals Received FDA Instructions for Diabetic Drug Actos The
drug Actos, also known as pioglitazone, has recently come under fire
due to studies showing a slight increased risk of bladder cancer in
those taking high doses of the drug or those who have taken Actos for
longer than two years. Manufactured by Takeda Pharmaceuticals of Japan,
the drug has shown huge gains in popularity in the past few years as it
quickly replaced the drug Avandia which suffered under claims of
increased risk of heart attack and death. Actos is Takeda’s tenth
best-selling drug, making over $3.4 billion dollars in the past year
alone. While the recent safety reviews have alarmed many who are
currently taking the drug, in fact there have been safety concerns
regarding Actos for several years. Warnings are Not NewAs
far back as 2006, the FDA issued instructions to Takeda regarding Actos
and ActoPlus Met, advising the company to make specific label changes
to the drug’s precautionary statements. These label changes were to
specifically include information regarding reports of bladder cancer in
those taking Actos. Takeda’s supplemental drug applications regarding
Actos were approved conditionally, so long as the agreed-upon text was
included in the drug’s labeling. The
FDA stipulated that the final printed label be identical to the
proposed labeling changes, and required Takeda to submit an electronic
version of the proposed label as well as 20 paper copies and fifteen
copies mounted on heavy-weight paper, however final approval was not
mandated prior to using the labels. Although these FDA instructions took
place nearly five years ago, it was only recently that more stringent
warnings regarding Actos were issued.
Benefit-Risk Balance Deemed Positive for Type 2 Diabetics Taking PioglitazoneFollowing
safety reviews of the drug pioglitazone—a medicine used in the
treatment of Type 2 diabetes—the European Medicines Agency delivered
their decision that while there is a marginally increased risk of
bladder cancer in those taking the drug, it remains a viable treatment
option for some patients. Pioglitazone, also sold under the brand name
Actos, is used along with a sensible diet and exercise program to
increase the body’s sensitivity to insulin, thereby controlling blood
sugar levels.Reducing Potential RisksThe
EMA’s conclusions following extensive study of the drug was that the
slight increased risk of bladder cancer could be alleviated through
implementation of a more stringent screening of potential patients.
Medical professionals are warned against prescribing pioglitazone in any
patients with a history of bladder cancer, and to exercise caution when
prescribing the drug to the elderly as well. Those
patients deemed good candidates for pioglitazone should nonetheless be
monitored closely every three to six months to ensure the benefits
continue to outweigh the risks. High Doses, Significant Duration LinkedThe
results of the controlled epidemiological studies determined that the
small risk associated with pioglitazone was seen primarily in those
patients who took the drug for significant lengths of time and in the
highest doses. Even though the studies showed only a 0.15% increase in
risk of bladder cancer this does not mean that those who are prescribed the drug for short term use have no risk at all of contracting bladder cancer.
FDA Issues Sterner Warnings to Manufacturers of Diabetic Drug ActosAlthough
the FDA issued recommendations regarding labeling cautions for the drug
Actos to manufacturer Takeda Pharmaceuticals in 2006, following further
safety reviews of the drug they have recently issued more stringent
instructions to the Japanese company. Actos, also known as pioglitazone
is used in the treatment of Type 2 diabetes to help control the levels
of sugar in the blood. Drugs Included, Safety Updates RequiredI
n
a letter to Takeda Pharmaceuticals the FDA states that supplemental new
drug applications for Actos, Actoplus Met, Actoplus Met XR and Duetact
were duly received and processed, and noted receipt of certain
amendments and risk evaluation assessments relating to Actos. Takeda was
notified of new safety information which the FDA deemed to be a
necessary inclusion of any future labeling of Actos. Further, the FDA
stated the safety updates must specifically address the potential risk
in increase of bladder cancer in those taking higher dosages or taking
the drug for extended periods of time. Specific Changes to Labeling of ActosThe
FDA asked that Takeda include under the warnings and precautions area
of the Actos label a statement that preclinical and clinical trials had
shown pioglitazone users experienced an increase in incidence of bladder
cancer. The Actos labels must state that those who have bladder cancer
or a prior history of bladder cancer should be extremely cautious when
using the drug. The label must additionally state that statistical
significance in bladder cancer risk is reached in those patients taking
Actos for longer than two years. More specifically, the wording that
taking Actos longer than twelve months increases the risk of developing
bladder cancer to a 40% statistical probability is to be included.Patient Counseling InformationThe
FDA’s advice to patients taking the drug includes immediately reporting
any signs or symptoms of urinary urgency, dysuria or macroscopic
hematuria to their treating physician, as these can be signs of bladder
cancer. Blood or red color in the urine or pain while urinating are all
serious side effects and should be relayed immediately to the patient’s
doctor. Actoplus Met, Actoplus Met XR and Duetact must all be labeled in
the same manner as Actos according to FDA findings.
No Recall Yet for Type 2 Diabetes Drug, Actos
The FDA has joined forces with France and
Germany regarding a warning about the Type 2 diabetes drug,
pioglitazone, however no recall is expected at this time. Pioglitazone,
also known as Actos, is manufactured by Takeda Pharmaceuticals, a
Japanese drug company. The drug currently accounts for some 27% of
Takeda’s annual revenues. 2008 saw this powerhouse diabetes medication
become the tenth best-selling prescription medication in the United
States. Over the past year, Takeda has accrued nearly $4.8 billion
dollars in revenues through worldwide sales of Actos. Clinical Studies of PioglitazonePre-clinical
studies—in which male rats were given body-weight equivalent doses of
Actos—showed an increase in the incidence of bladder cancer while two
subsequent clinical studies using human subjects also revealed an
elevated risk of bladder cancer. Due to these findings, the FDA mandated
that the potential risks be revealed on the label of the drug, ordering
a safety review in September, 2010. Takeda additionally agreed to
carry out a ten-year observational study in those diabetic patients
currently taking Actos, to be conducted on patients from Kaiser
Permanente Northern California Health Plan.
European Medicines Agency Scientific Studies on PioglitazoneThe
European Medicines Agency released a scientific study on the benefits
and risks of the drug pioglitazone, also known as Actos, in January of
2007. This drug is currently used as a single treatment for Type 2
diabetes or in a dual combination form with metformin or sulphonylurea.
When used alone, pioglitazone is typically used as therapy for the
overweight patient whose Type 2 diabetes is not being controlled through
diet and exercise and for whom the drug metformin is inappropriate. The
combination drug is most often used in those patients who have
insufficient glycemic control despite taking metformin alone or for
those patients who have shown a level of intolerance to metformin. The
results of the study showed that when pioglitazone was prescribed in
conjunction with other anti-diabetic therapies such as insulin, the risk
of macrovascular disease was greatly reduced. Macrovascular disease is
common in those with long-term diabetes and refers to a disease of the
large blood vessels in the body. Clinical Support for Pioglitazone ApplicationEvidence
was submitted which supported the application of pioglitazone,
including four clinical trial reports which studied the safety of the
drug when used in conjunction with insulin therapy. The studies were
conducted according to prevailing ethical standards, and were random,
double-blind, placebo controlled. First Pioglitazone Study—PNFP-014Pioglitazone
was administered both in 15 mg dosages as well as 30 mg dosages in
combination with insulin then compared with using insulin therapy alone.
Participants in the studies were between the ages of 30 and 75, and had
been on a fixed dose of insulin for at least a month prior to beginning
the study. The mean baseline age was 57 years, with an average BMI of
33.6. Nearly 3/4ths of the participants in the study were Caucasian,
with slightly more than half being female. Although the baseline
systolic blood pressure was minimally higher in the group receiving
pioglitazone plus insulin as opposed to the group receiving insulin
alone, there were no other baseline variables involved. The patients who
received both pioglitazone and insulin showed statistical decreases in
the HbA1c levels which measure the average amount of sugar in the blood
over a period of three months, and is different from glucose
measurements. The HbA1c levels essentially give the physician an
indication of how well the diabetes is being controlled.
