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® 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.
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.
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.
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.
