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® 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.
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.
