Determining Whether You Have an Actos Case
Hundreds of thousands of patients who have taken the drug Actos over the past few years—believing the drug to be safe—have been very disillusioned to find that the drug can have some potentially very serious side effects. Actos is a drug which was developed for the treatment of Type 2 diabetes and works by helping the body restore its normal response to insulin, effectively lowering blood sugar. When high blood sugar is not consistently controlled, kidney damage, blindness, nerve problems and even the loss of limbs become possible medical issues. The control of Type 2 diabetes is also necessary to avoid a debilitating heart attack or stroke. Therefore, when a drug such as Actos seems to do a good job of lowering blood sugar, it becomes a very popular prescription drug. So popular that in spite of the recent rash of lawsuits against Takeda—the manufacturers of Actos—profits have only been dampened by approximately 13%. The pharmaceutical giant is still enjoys some $2.2 billion dollars in annual profits, down from an all-time high of over 4 billion dollars in annual profits. If you have taken Actos you may be wondering whether you might have an Actos case and be entitled to damages.
The FDA issued a warning which cautions patients with a history, diagnosis or heightened risk of bladder cancer to consider an alternative diabetes treatment to Actos. Although this warning sounds fairly mild, drug safety watchdogs are urging anyone who is currently taking Actos to speak to their doctor about an alternative drug with less risk factor and are strongly urging those who have taken the drug in the past to ask their doctor to set up a bladder cancer screening. The common side effects of Actos generally include upper respiratory infections, headache, sinus infection, muscle pain, tooth problems, sore throat and swelling or water weight gain. Anyone who has had symptoms which can suggest bladder cancer such as blood in the urine, pain upon urination, back or stomach pain, or an urgent need to urinate should immediately seek medical attention. Because Actos has also been tied to an increased risk of heart failure, any patient who notices swelling of the feet, a sudden increase in weight and shortness of breath should also seek immediate medical attention. In conjunction these symptoms can suggest congestive heart failure and a buildup of fluid in the lungs. In short, if you took Actos for a period of more than twelve months, or in very high dosages, you may be eligible to file an Actos lawsuit.
Could Harm from Actos Translate Into Damages?
Lawsuits resulting from bladder cancer believed to be caused by Actos started in August of 2011 with thousands expected to follow as the harmful effects of the drug continue to be investigated. Many of these lawsuits allege that Takeda either knew or should have known the long-term effects of the drug, primarily the increased risk of bladder cancer in those taking higher dosages or taking Actos for an extended period of time. The FDA did not release a safety communication regarding these risks until June 15, 2011, basing their decision on an ongoing ten-year study of the serious side effects of Actos. Among this group of 193,000 patients taking Actos, a five-year interim study revealed no overall increase in bladder cancer, however showed significantly increased risks of the disease in those taking Actos for an extended period of time or in higher dosages.
Compared to those who had never taken Actos study participants who took the drug for longer than twelve months were found to have a forty percent higher risk of developing bladder cancer. While every case is unique, the damages awarded in Actos settlements will be based on a variety of factors. Takeda’s failure to warn those taking Actos of potential bladder cancer or heart failure risks will certainly factor into the equation, as well as the extent of the damages you have suffered. Those who have already been diagnosed with bladder cancer or heart failure which can be linked to the use of Actos obviously have easily assessable damages. Even those who have not yet suffered ill health effects from Actos use should not discount a lawsuit for potential harm. If Takeda Pharmaceuticals knew the harmful effects of Actos before placing it on the market and used financial means to hide this knowledge, then essentially any person who has taken Actos may be eligible to take part in the Actos class action lawsuit.
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Showing posts with label actos lawyer. Show all posts
Showing posts with label actos lawyer. Show all posts
Actos Discussions Part 2: Dangers of the Drug
Could Your Heart Failure Be Linked to Actos?
Links to higher heart disease rates have been associated with the use of Actos, and, in fact, Actos may cause as many heart problems as GlaxoSmithKline’s drug, Avandia. The American Heart Association reported that studies showed patients taking either diabetes drug were at least four times as likely to experience heart attacks, heart failure or even death. When a 2007 study on Avandia showed a 43 percent higher chance of heart attack, Actos quickly became the market leader. A subsequent study on both drugs showed that 602 Avandia users and 599 Actos users in the study suffered either a heart attack, heart failure or both, with 217 deaths in each group. The latest study regarding Actos in the journal Lancet found the risk for heart failure greatest among those patients with a prior history of heart disease and heart failure, however overall the relative risk when taking Actos was as much as 72 percent higher than those not taking the drug. Both Glaxo and Takeda dispute the results of these negative studies, citing a study published in the Journal of the American Medical Association which suggests Actos might actually cut the risk of heart attack, stroke and death.
Link between Actos and Heart Failure
Actos is in a class of drugs known as thiazolidinediones, whose use has long been attributed to certain liver and cardiovascular health issues. A listed side effect of Actos includes the threat of congestive heart failure with the link between Actos and congestive heart failure being so undeniable that in 2007 the FDA escalated warnings regarding heart disease when taking the drug. Actos causes the body to retain excess fluid, leading to swelling and weight gain. This extra body fluid can worsen some heart problems, leading to heart failure or can actually cause heart problems.
When Actos causes swelling in the body, this swelling also occurs around the heart, rendering it unable to effectively pump blood throughout the body. As fluid builds up around the heart and lungs, it becomes more difficult for the heart to pump, causing it to become less and less efficient. This can lead to shortness of breath, trouble breathing when lying down, a feeling of excessive tiredness or an unusually rapid increase in weight. After an intense debate over the cardiovascular risks of Actos, the FDA agreed to surround the heart risk warnings on Actos with an emphatic black outline commonly known as a black box warning. This black box warning is the strongest FDA label change which can be added to any drug on the market.
Link Between Actos and Bladder Cancer
The FDA issued its safety announcement regarding the connection between using Actos for more than one year and the risk of bladder cancer on June 15, 2011. The bladder lies in the center of the lower part of the abdomen, and its primary purpose is to store urine prior to excreting it from the body. When cells in the bladder become cancerous, a tumor can form. Actos helps diabetics use their own insulin better by hitting at least two of the three main PPAR receptors known as the Gamma and Alpha receptors. The Gamma receptor works on glucose while the Alpha receptor affects cholesterol. Actos appears to have a higher affinity with the Alpha receptor which is why it does a good job on raising good cholesterol and lowering triglycerides.
It has been hypothesized that the way in which Actos reacts with these receptors may also be the reason it contributes to the risk of bladder cancer. Potential symptoms of bladder cancer include bloody urine, chronic and persistent infections of the bladder, a strong urge to urinate or pain and burning during urination. X-rays may reveal an abnormality in the bladder walls, or red blood cells found in the urine during lab tests. If the bladder is swelling, a biopsy may be done or a growth in the bladder could be discovered through a CT or MRI scan. Bladder cancer is typically treated with removal of the tumor, surgical removal of all or part of the bladder or with drugs which help the immune system fight the cancer.
Could Actos Damage Your Liver or Kidneys?
In addition to potentially damaging the heart and bladder, Actos may also be linked to rhabdomyolysis which occurs when muscle fibers rapidly bread down releasing proteins and myoglobin into the blood stream. Myoglobin can be toxic to the kidneys, leading to the development of rhabdomyolysis. Symptoms of this serious kidney disease include muscle pain or tenderness, stiffness or weakness in the joints and dark-colored urine. Actos has also been documented to cause elevated liver enzymes, a precursor to liver damage. Anyone who is considering taking Actos should have their liver enzymes tested before they start taking the drug, and should periodically monitor the liver enzymes while on Actos.
What to Do If You Think You Have Suffered Damage from Actos
Any person who has suffered symptoms of bladder cancer, heart disease, kidney or liver failure or any other serious effects from taking Actos should definitely educate themselves about the potential risks of the drug and should seek legal representation. Many cases have statutes of limitations, or time limits and you will want to know how these time constraints may affect your potential case. While there are no absolute guarantees when you file a lawsuit, your attorney can offer you knowledgeable guidance in pursuing financial compensation for the injuries you sustained as a result of taking Actos. This compensation can cover your medical expenses, the cost of past and ongoing therapies associated with your Actos health damages, and any other costs associated with your care. Lawsuits regarding defective drug injuries can be extremely complex requiring a thorough investigation into medical records, testimony by qualified physicians and the resources to fight a large pharmaceutical company. If you believe you have suffered harm to your health through taking Actos, consult an experienced personal injury attorney as soon as possible.
Links to higher heart disease rates have been associated with the use of Actos, and, in fact, Actos may cause as many heart problems as GlaxoSmithKline’s drug, Avandia. The American Heart Association reported that studies showed patients taking either diabetes drug were at least four times as likely to experience heart attacks, heart failure or even death. When a 2007 study on Avandia showed a 43 percent higher chance of heart attack, Actos quickly became the market leader. A subsequent study on both drugs showed that 602 Avandia users and 599 Actos users in the study suffered either a heart attack, heart failure or both, with 217 deaths in each group. The latest study regarding Actos in the journal Lancet found the risk for heart failure greatest among those patients with a prior history of heart disease and heart failure, however overall the relative risk when taking Actos was as much as 72 percent higher than those not taking the drug. Both Glaxo and Takeda dispute the results of these negative studies, citing a study published in the Journal of the American Medical Association which suggests Actos might actually cut the risk of heart attack, stroke and death.
Link between Actos and Heart Failure
Actos is in a class of drugs known as thiazolidinediones, whose use has long been attributed to certain liver and cardiovascular health issues. A listed side effect of Actos includes the threat of congestive heart failure with the link between Actos and congestive heart failure being so undeniable that in 2007 the FDA escalated warnings regarding heart disease when taking the drug. Actos causes the body to retain excess fluid, leading to swelling and weight gain. This extra body fluid can worsen some heart problems, leading to heart failure or can actually cause heart problems.
When Actos causes swelling in the body, this swelling also occurs around the heart, rendering it unable to effectively pump blood throughout the body. As fluid builds up around the heart and lungs, it becomes more difficult for the heart to pump, causing it to become less and less efficient. This can lead to shortness of breath, trouble breathing when lying down, a feeling of excessive tiredness or an unusually rapid increase in weight. After an intense debate over the cardiovascular risks of Actos, the FDA agreed to surround the heart risk warnings on Actos with an emphatic black outline commonly known as a black box warning. This black box warning is the strongest FDA label change which can be added to any drug on the market.
Link Between Actos and Bladder Cancer
The FDA issued its safety announcement regarding the connection between using Actos for more than one year and the risk of bladder cancer on June 15, 2011. The bladder lies in the center of the lower part of the abdomen, and its primary purpose is to store urine prior to excreting it from the body. When cells in the bladder become cancerous, a tumor can form. Actos helps diabetics use their own insulin better by hitting at least two of the three main PPAR receptors known as the Gamma and Alpha receptors. The Gamma receptor works on glucose while the Alpha receptor affects cholesterol. Actos appears to have a higher affinity with the Alpha receptor which is why it does a good job on raising good cholesterol and lowering triglycerides.
It has been hypothesized that the way in which Actos reacts with these receptors may also be the reason it contributes to the risk of bladder cancer. Potential symptoms of bladder cancer include bloody urine, chronic and persistent infections of the bladder, a strong urge to urinate or pain and burning during urination. X-rays may reveal an abnormality in the bladder walls, or red blood cells found in the urine during lab tests. If the bladder is swelling, a biopsy may be done or a growth in the bladder could be discovered through a CT or MRI scan. Bladder cancer is typically treated with removal of the tumor, surgical removal of all or part of the bladder or with drugs which help the immune system fight the cancer.
Could Actos Damage Your Liver or Kidneys?
In addition to potentially damaging the heart and bladder, Actos may also be linked to rhabdomyolysis which occurs when muscle fibers rapidly bread down releasing proteins and myoglobin into the blood stream. Myoglobin can be toxic to the kidneys, leading to the development of rhabdomyolysis. Symptoms of this serious kidney disease include muscle pain or tenderness, stiffness or weakness in the joints and dark-colored urine. Actos has also been documented to cause elevated liver enzymes, a precursor to liver damage. Anyone who is considering taking Actos should have their liver enzymes tested before they start taking the drug, and should periodically monitor the liver enzymes while on Actos.
What to Do If You Think You Have Suffered Damage from Actos
Any person who has suffered symptoms of bladder cancer, heart disease, kidney or liver failure or any other serious effects from taking Actos should definitely educate themselves about the potential risks of the drug and should seek legal representation. Many cases have statutes of limitations, or time limits and you will want to know how these time constraints may affect your potential case. While there are no absolute guarantees when you file a lawsuit, your attorney can offer you knowledgeable guidance in pursuing financial compensation for the injuries you sustained as a result of taking Actos. This compensation can cover your medical expenses, the cost of past and ongoing therapies associated with your Actos health damages, and any other costs associated with your care. Lawsuits regarding defective drug injuries can be extremely complex requiring a thorough investigation into medical records, testimony by qualified physicians and the resources to fight a large pharmaceutical company. If you believe you have suffered harm to your health through taking Actos, consult an experienced personal injury attorney as soon as possible.
Actos® Adverse Effects
Many 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 Actos
The 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.
More Serious Adverse Effects from Actos
In general, the side effects of Actos were found to be similar to the side effects of Actos used in combination with sulfonylurea, metformin or insulin other than an increase in edema when Actos was combined with insulin therapy. Almost 200,000 patients with Type 2 Diabetes who took Actos to control their disease, were involved in a Northern California research study. Alarmingly, the study found that those taking Actos for any length of time past twelve months were at a 40% higher risk of developing bladder cancer than those not taking the drug. Prior to the release of this study, Takeda disclosed no cancer warnings on their labeling information sheet or the patient medication guide. Other studies are now indicating that those patients who took the highest dosages of Actos or took it for at least two years with a cumulative dosage of greater than 28,000 mg faced the highest risks of developing bladder cancer.
While the FDA has compelled Takeda to adjust their labeling to include warnings about possible increased risks of bladder cancer, the United States is holding off pulling the drug until results of further studies are in. Other countries are not so relaxed about the drug with New Zealand scheduling a recall of Actos, and France and Germany already suspending sales of the drug. The French National Health Insurance Plan studied data from a million and a half patients with Type 2 diabetes, finding a “statistically significant increase” in the risk of bladder cancer in those taking Actos as compared with those taking other anti-diabetic drugs. Unfortunately the bladder cancer risk is not the only serious adverse effect noted in those taking Actos.
Cardiovascular Risks and Side Effects from Actos
As noted, once the cardiovascular risks of the Type 2 diabetes drug Avandia were made public, Actos was seen as a much safer alternative, causing sales to skyrocket. Both Avandia and Actos belong to the class of drugs known as thizolidinediones which are considered to be among the strongest medications for Type 2 diabetes. Both Actos and Avandia work by reducing body tissue insulin resistance while adjusting cholesterol levels simultaneously. The risk of heart attack, stroke and cardiovascular disease was found to be 30-40 percent higher among those taking Avandia, and initially Actos was not felt to carry this same risk.
In 2010, however, the FDA stated Actos would carry what is known as a “black box warning” regarding cardiovascular risk. Those with Type 2 diabetes who also have any type of heart disease, no matter how mild, or any kidney disease could be at a significantly increased risk of developing congestive heart failure while taking Actos. Congestive heart failure occurs when the heart is unable to pump sufficient blood to maintain adequate circulation in the body, leading to a fluid buildup in the lungs.
Bone Fractures Seen in Certain Groups Taking Actos
In another study, women over the age of 50 who suffered from broken bones and osteoporosis were found to be over 70% as likely to have been prescribed a thiazolidinedione drug such as Actos. The types of fractures seen in this study were not the same sort as those seen in people with osteoporosis, such as spine and hip fractures, but also included arm and leg fractures. In short, women with Type 2 diabetes over the age of 50 who were taking a thiazolidinedione drug were much more likely to suffer from some form of osteoporosis and bone fractures.
Actos has also been shown to raise the level of liver enzymes, meaning there is a possibility of liver damage when taking the drug. If you have experienced any of the side effects associated with Actos, it is imperative you consult your physician.
“Minor” Side Effects of Actos
The 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.
More Serious Adverse Effects from Actos
In general, the side effects of Actos were found to be similar to the side effects of Actos used in combination with sulfonylurea, metformin or insulin other than an increase in edema when Actos was combined with insulin therapy. Almost 200,000 patients with Type 2 Diabetes who took Actos to control their disease, were involved in a Northern California research study. Alarmingly, the study found that those taking Actos for any length of time past twelve months were at a 40% higher risk of developing bladder cancer than those not taking the drug. Prior to the release of this study, Takeda disclosed no cancer warnings on their labeling information sheet or the patient medication guide. Other studies are now indicating that those patients who took the highest dosages of Actos or took it for at least two years with a cumulative dosage of greater than 28,000 mg faced the highest risks of developing bladder cancer.
While the FDA has compelled Takeda to adjust their labeling to include warnings about possible increased risks of bladder cancer, the United States is holding off pulling the drug until results of further studies are in. Other countries are not so relaxed about the drug with New Zealand scheduling a recall of Actos, and France and Germany already suspending sales of the drug. The French National Health Insurance Plan studied data from a million and a half patients with Type 2 diabetes, finding a “statistically significant increase” in the risk of bladder cancer in those taking Actos as compared with those taking other anti-diabetic drugs. Unfortunately the bladder cancer risk is not the only serious adverse effect noted in those taking Actos.
Cardiovascular Risks and Side Effects from Actos
As noted, once the cardiovascular risks of the Type 2 diabetes drug Avandia were made public, Actos was seen as a much safer alternative, causing sales to skyrocket. Both Avandia and Actos belong to the class of drugs known as thizolidinediones which are considered to be among the strongest medications for Type 2 diabetes. Both Actos and Avandia work by reducing body tissue insulin resistance while adjusting cholesterol levels simultaneously. The risk of heart attack, stroke and cardiovascular disease was found to be 30-40 percent higher among those taking Avandia, and initially Actos was not felt to carry this same risk.
In 2010, however, the FDA stated Actos would carry what is known as a “black box warning” regarding cardiovascular risk. Those with Type 2 diabetes who also have any type of heart disease, no matter how mild, or any kidney disease could be at a significantly increased risk of developing congestive heart failure while taking Actos. Congestive heart failure occurs when the heart is unable to pump sufficient blood to maintain adequate circulation in the body, leading to a fluid buildup in the lungs.
Bone Fractures Seen in Certain Groups Taking Actos
In another study, women over the age of 50 who suffered from broken bones and osteoporosis were found to be over 70% as likely to have been prescribed a thiazolidinedione drug such as Actos. The types of fractures seen in this study were not the same sort as those seen in people with osteoporosis, such as spine and hip fractures, but also included arm and leg fractures. In short, women with Type 2 diabetes over the age of 50 who were taking a thiazolidinedione drug were much more likely to suffer from some form of osteoporosis and bone fractures.
Actos has also been shown to raise the level of liver enzymes, meaning there is a possibility of liver damage when taking the drug. If you have experienced any of the side effects associated with Actos, it is imperative you consult your physician.
Actos® and Bladder Cancer
Recent 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.
Shaped like a balloon, the bladder resides in the lower regions of the abdomen and its primary function is storage for urine. Urine is a liquid waste made by the kidneys when they clean the body’s blood—until it is passed from the body. Bladder cancer typically begins in the cells which line the bladder and risk factors include smoking, certain infections, being male, white and elderly, eating a diet which is high in fats and fried foods, and being exposed to specific carcinogenic chemicals commonly used in hairdressing, textile production, paints and rubber manufacturing. Symptoms of bladder cancer include frequent urination, blood in the urine or pain during urination, and lower back pain. Procedures for determining bladder cancer include CT scans, urinalysis, an internal exam, or a cystoscopy.
The chances of recovering from bladder cancer depends largely on what stage the cancer is in when discovered as well as the patient’s age and overall health status. Treatments include chemotherapy, surgery and radiation. The five-year survival rate for patients with early stage bladder cancer is approximately 85%, however in patients with more advanced bladder cancer who have undergone chemotherapy and/or radiation, the five-year survival rate is only 60-75%. Over 14,000 deaths occur each year from bladder cancers.
Several studies have linked the use of Actos for periods of longer than a year or in higher dosages to as much as a 42% increase in the incidence of bladder cancer. The potential risk of Actos users developing bladder cancer has been known for some time; the FDA’s Adverse Event Reporting System has found that 31 cases of bladder cancer were recorded between 2004 and 2009 in patients being treated with an anti-diabetic drug containing pioglitazone, such as Actos. A study of more than 190,000 patients with Type 2 diabetes who were enrolled in the Kaiser Permanente Northern California health plan showed that while there was not a significant overall increased risk of bladder cancer, those patients who were taking higher doses or were taking Actos for longer than twelve months had as much as a 40% increased chance of developing bladder cancer as compared to patients who had never used the drug. The participants in this study were at least forty years old.
The FDA, citing the results of the study done by Takeda as well as another study done by the French National Health Insurance Plan, simply recommended that physicians avoid prescribing Actos in patients suffering from active bladder cancer or in those with a history of bladder cancer. France apparently looked at the results of the tests a little differently, suspending the use of Actos while Germany recommended that no new patients be started on the drug. The FDA has asked any Actos users who have had adverse events while taking the drug to report those events immediately to the FDA’s MedWatch.
Dr. Joseph Giangola, the medical director of diabetes at Hackensack University Medical Center, remains solid in his belief that the benefits of Actos still outweigh the possible risk of developing bladder cancer. Although Dr. Giangola states he is cautious when prescribing Actos, he reminds that there is essentially no drug currently on the market which can effectively replace Actos to influence insulin resistance. The FDA cautions patients to immediately contact their doctor should they have any symptoms of bladder cancer such as blood or red color in the urine, pain upon urination or pain in the lower back and/or abdomen. Takeda Pharmaceuticals states that it will remain positive about the therapeutic benefits of Actos, while continuing its ten-year study on the potential for Actos to cause 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.
Shaped like a balloon, the bladder resides in the lower regions of the abdomen and its primary function is storage for urine. Urine is a liquid waste made by the kidneys when they clean the body’s blood—until it is passed from the body. Bladder cancer typically begins in the cells which line the bladder and risk factors include smoking, certain infections, being male, white and elderly, eating a diet which is high in fats and fried foods, and being exposed to specific carcinogenic chemicals commonly used in hairdressing, textile production, paints and rubber manufacturing. Symptoms of bladder cancer include frequent urination, blood in the urine or pain during urination, and lower back pain. Procedures for determining bladder cancer include CT scans, urinalysis, an internal exam, or a cystoscopy.
The chances of recovering from bladder cancer depends largely on what stage the cancer is in when discovered as well as the patient’s age and overall health status. Treatments include chemotherapy, surgery and radiation. The five-year survival rate for patients with early stage bladder cancer is approximately 85%, however in patients with more advanced bladder cancer who have undergone chemotherapy and/or radiation, the five-year survival rate is only 60-75%. Over 14,000 deaths occur each year from bladder cancers.
Several studies have linked the use of Actos for periods of longer than a year or in higher dosages to as much as a 42% increase in the incidence of bladder cancer. The potential risk of Actos users developing bladder cancer has been known for some time; the FDA’s Adverse Event Reporting System has found that 31 cases of bladder cancer were recorded between 2004 and 2009 in patients being treated with an anti-diabetic drug containing pioglitazone, such as Actos. A study of more than 190,000 patients with Type 2 diabetes who were enrolled in the Kaiser Permanente Northern California health plan showed that while there was not a significant overall increased risk of bladder cancer, those patients who were taking higher doses or were taking Actos for longer than twelve months had as much as a 40% increased chance of developing bladder cancer as compared to patients who had never used the drug. The participants in this study were at least forty years old.
The FDA, citing the results of the study done by Takeda as well as another study done by the French National Health Insurance Plan, simply recommended that physicians avoid prescribing Actos in patients suffering from active bladder cancer or in those with a history of bladder cancer. France apparently looked at the results of the tests a little differently, suspending the use of Actos while Germany recommended that no new patients be started on the drug. The FDA has asked any Actos users who have had adverse events while taking the drug to report those events immediately to the FDA’s MedWatch.
Dr. Joseph Giangola, the medical director of diabetes at Hackensack University Medical Center, remains solid in his belief that the benefits of Actos still outweigh the possible risk of developing bladder cancer. Although Dr. Giangola states he is cautious when prescribing Actos, he reminds that there is essentially no drug currently on the market which can effectively replace Actos to influence insulin resistance. The FDA cautions patients to immediately contact their doctor should they have any symptoms of bladder cancer such as blood or red color in the urine, pain upon urination or pain in the lower back and/or abdomen. Takeda Pharmaceuticals states that it will remain positive about the therapeutic benefits of Actos, while continuing its ten-year study on the potential for Actos to cause bladder cancer.
Actos® and Cardiovascular Dangers
The 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.
In fact, as early on as 1999, when Avandia and related drug types first hit the market, Dr. John Buse warned about the potential cardiovascular dangers inherent in this type of drug. Even though Dr. Buse was a prominent endocrinologist as well as the new president of the American Diabetes Association, his concerns were met with threats by the manufacturers of the drugs, and no action was taken to investigate the cardiovascular side effects of Actos. Because the disease of diabetes in itself increases the risk of cardiovascular complications, the fact that the drug used to treat the disease may carry serious cardiovascular risks is of significant concern. Older patients appear to be at an even greater risk of cardiovascular problems than their younger counterparts.
Patients who continue to take Actos as treatment for their Type 2 diabetes are warned to seek medical attention immediately should they experience any symptoms of cardiovascular disease. Symptoms can include edema, shortness of breath, extreme exhaustion, chest pain or discomfort, dizziness, irregular heartbeats, nausea or pain in one or both arms, your left shoulder, the neck, jaw or back. In the case of a heart attack, the symptoms can develop rapidly however in most cases of cardiovascular problems, symptoms will develop over a period of days or even months. Patients who already suffer from cardiac problems should not take Actos, as it could worsen those problems, leading to heart failure, even though it appears that many physicians have been ignoring the 2007 black box warning and continuing to prescribe Actos to patients with known cardiovascular issues.
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.
In fact, as early on as 1999, when Avandia and related drug types first hit the market, Dr. John Buse warned about the potential cardiovascular dangers inherent in this type of drug. Even though Dr. Buse was a prominent endocrinologist as well as the new president of the American Diabetes Association, his concerns were met with threats by the manufacturers of the drugs, and no action was taken to investigate the cardiovascular side effects of Actos. Because the disease of diabetes in itself increases the risk of cardiovascular complications, the fact that the drug used to treat the disease may carry serious cardiovascular risks is of significant concern. Older patients appear to be at an even greater risk of cardiovascular problems than their younger counterparts.
Patients who continue to take Actos as treatment for their Type 2 diabetes are warned to seek medical attention immediately should they experience any symptoms of cardiovascular disease. Symptoms can include edema, shortness of breath, extreme exhaustion, chest pain or discomfort, dizziness, irregular heartbeats, nausea or pain in one or both arms, your left shoulder, the neck, jaw or back. In the case of a heart attack, the symptoms can develop rapidly however in most cases of cardiovascular problems, symptoms will develop over a period of days or even months. Patients who already suffer from cardiac problems should not take Actos, as it could worsen those problems, leading to heart failure, even though it appears that many physicians have been ignoring the 2007 black box warning and continuing to prescribe Actos to patients with known cardiovascular issues.
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 became a huge money-maker relatively quickly following its approval in 1999, then when Avandia—the only close competitor of Actos—was found in 2007 to sharply increase the risk of heart attacks, the sales of Actos nearly doubled. Actos is quite effective in controlling blood sugar and boosting the body’s insulin sensitivity, but it may have been prescribed too often prior to learning the extent of its more serious side effects. Takeda Pharmaceuticals has issued the mid-point results of their own study regarding the safety of Actos, and while the five year results showed no overall increased risk of bladder cancer, among those taking the drug in higher dosages or for longer than twelve months, the risk for bladder cancer jumps by as much as 40%. The FDA believes further studies are warranted before Actos is pulled from the shelves in America, however the flurry of lawsuits may make a difference in that decision.
Although there are already hundreds of potential lawsuits against the manufacturer of Actos, the Japanese company has thus far declined to comment other than issuing a statement reaffirming its commitment to keeping Actos available for those who need it. An April study published in the Journal of Diabetes Care found that those who had used Actos for longer than two years had a definite increase in their risk of bladder cancer. Advocates for the drug remind those who want to pull it from the market that approximately 28 cases of bladder cancer a year for every 100,000 people taking the drug is not that statistically significant. Those patients who have developed bladder cancer as a direct result of taking Actos may beg to differ.
The new safety issues which have risen regarding Actos and bladder cancer could potentially cost Takeda more than the payout for the lawsuits they will face. The Actos patent is set to expire in August of 2012, and not only will Actos fail to make the expected revenues in its final months prior to that time, the prospects for two more of Takeda’s experimental drugs may be severely dampened. Because one of those drugs is a combination drug containing both Actos and alogliptin while the other is straight alogliptin, it is fairly likely that the combo drug is out of the running due to the current safety concerns surrounding Actos.
Although it is not expected that the Actos bladder cancer litigation will hit the extreme levels of the Vioxx 2004 painkiller settlement—50,000 lawsuits and a $4.85 billion settlement—the makers of Avandia, a drug in the same class as Actos, have set aside over $400 million dollars for settlements. Many physicians switched their patients from Avandia to Actos believing it would be the safer choice however it is now being shown that it has many of the same dangers as well as the increased risk of bladder cancer. Actos attorneys are claiming Takeda knew many years ago of the increased risk of bladder cancer their drug could cause, yet did nothing to warn patients. A two-year animal study prior to the release of Actos showed that male rats developed tumors after receiving doses of Actos, yet the drug was pushed through in spite of those results, and launched with no warnings regarding potential bladder cancer risks.
Potentially thousands of those who were harmed by taking Actos could file lawsuits against Takeda and Eli Lilly, and it is expected that these suits could take years to fully resolve. These suits may include those who developed bladder cancer, those who suffered congestive heart failure or other heart issues, those who suffered osteoporosis and bone fractures, and those who developed macular edema from the drug. The initial estimates are that the “typical” settlement could be between $75,000 and $360,000 for those who were harmed by taking Actos for their Type 2 diabetes.
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 became a huge money-maker relatively quickly following its approval in 1999, then when Avandia—the only close competitor of Actos—was found in 2007 to sharply increase the risk of heart attacks, the sales of Actos nearly doubled. Actos is quite effective in controlling blood sugar and boosting the body’s insulin sensitivity, but it may have been prescribed too often prior to learning the extent of its more serious side effects. Takeda Pharmaceuticals has issued the mid-point results of their own study regarding the safety of Actos, and while the five year results showed no overall increased risk of bladder cancer, among those taking the drug in higher dosages or for longer than twelve months, the risk for bladder cancer jumps by as much as 40%. The FDA believes further studies are warranted before Actos is pulled from the shelves in America, however the flurry of lawsuits may make a difference in that decision.
Although there are already hundreds of potential lawsuits against the manufacturer of Actos, the Japanese company has thus far declined to comment other than issuing a statement reaffirming its commitment to keeping Actos available for those who need it. An April study published in the Journal of Diabetes Care found that those who had used Actos for longer than two years had a definite increase in their risk of bladder cancer. Advocates for the drug remind those who want to pull it from the market that approximately 28 cases of bladder cancer a year for every 100,000 people taking the drug is not that statistically significant. Those patients who have developed bladder cancer as a direct result of taking Actos may beg to differ.
The new safety issues which have risen regarding Actos and bladder cancer could potentially cost Takeda more than the payout for the lawsuits they will face. The Actos patent is set to expire in August of 2012, and not only will Actos fail to make the expected revenues in its final months prior to that time, the prospects for two more of Takeda’s experimental drugs may be severely dampened. Because one of those drugs is a combination drug containing both Actos and alogliptin while the other is straight alogliptin, it is fairly likely that the combo drug is out of the running due to the current safety concerns surrounding Actos.
Although it is not expected that the Actos bladder cancer litigation will hit the extreme levels of the Vioxx 2004 painkiller settlement—50,000 lawsuits and a $4.85 billion settlement—the makers of Avandia, a drug in the same class as Actos, have set aside over $400 million dollars for settlements. Many physicians switched their patients from Avandia to Actos believing it would be the safer choice however it is now being shown that it has many of the same dangers as well as the increased risk of bladder cancer. Actos attorneys are claiming Takeda knew many years ago of the increased risk of bladder cancer their drug could cause, yet did nothing to warn patients. A two-year animal study prior to the release of Actos showed that male rats developed tumors after receiving doses of Actos, yet the drug was pushed through in spite of those results, and launched with no warnings regarding potential bladder cancer risks.
Potentially thousands of those who were harmed by taking Actos could file lawsuits against Takeda and Eli Lilly, and it is expected that these suits could take years to fully resolve. These suits may include those who developed bladder cancer, those who suffered congestive heart failure or other heart issues, those who suffered osteoporosis and bone fractures, and those who developed macular edema from the drug. The initial estimates are that the “typical” settlement could be between $75,000 and $360,000 for those who were harmed by taking Actos for their Type 2 diabetes.
Actos® European Recall and FDA Stance
A 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.
This study led Germany to change their initial warnings to physicians to include the statement that no new patients should be prescribed Actos due to its dangerous side effects. While the EMA did not issue an Actos recall for the entire European Union, it confirmed that this particular Type 2 diabetes drug put its users at a much greater risk for developing severe side effects, including bladder cancer. New Zealand has now scheduled its own recall of Actos due to perceived risks including heart failure, heart attack, stroke and bladder cancer just like the drug’s predecessor, Avandia.
Germany and France based their recall of Actos on a French study indicating an increased risk of bladder cancer in those taking the drug. The study was done on over 150,000 study participants who had taken Actos between 2006 and 2009, with findings of a 22% increase in bladder cancer in those who took Actos to control their Type 2 diabetes. In those who were using higher dosages of Actos, that figure was as high as a 50% increased risk of bladder cancer.
In 2007 the FDA recalled Actos for improper warning labels, however once that issue was resolved they allowed the drug back on the market. At present the FDA continues to examine the results of a ten year study done on over a million patients who have regularly taken Actos. Although mid-point results from the study indicated a possibility of increased bladder cancer risk, the results were less than definitive, leading the FDA to allow Actos to remain on the market until further results are in.
Actos is routinely prescribed for Type 2 diabetes when it is not being well-controlled by diet and exercise alone. Actos is manufactured by Takeda Pharmaceuticals, a Japanese corporation, and co-marketed by Eli Lilly in the United States. Actos is Takeda’s best-selling drug, making them over $3.4 billion dollars in 2010 alone. The FDA approved Actos in 1999, and it quickly became the most prescribed alternative to Avandia which had been linked to stroke and heart attack. The FDA issued a black box warning to be placed on Actos labels in 2007 after it was determined that Actos could increase the risk of congestive heart failure. June, 2011 saw yet another revision to the Actos warning label which now clearly states to Actos patients that they face an increased risk of bladder cancer should they take the drug for longer than a year. This FDA warning also includes combination drugs such as ActoplusMet, ActoplusMet RX and Duetact. It is estimated that Actos lawsuits will lead to payments between one and five billion dollars on at least 13,000 lawsuits.
Takeda Pharmaceuticals will continue its ten-year observational cohort study which included nearly 200,000 patients. The interim analysis was done in 2008 among patients with a median duration of Actos therapy of two years, and a range of three months to eight and a half years. After adjustments were made for age, sex, use of tobacco products and use of other diabetes medications there appeared to be no significant increase in the risk for bladder cancer in those who had taken the medication for short amounts of time or in small dosages. Those who had taken Actos for more than twelve months, however, showed an almost 40% increase in bladder cancer risk. Other studies have shown similar risks in those taking higher dosages of Actos or taking it for longer periods of time. Some believe the FDA approves drugs too quickly and is not as concerned with possibly jeopardizing patient safety as other countries appear to be.
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.
This study led Germany to change their initial warnings to physicians to include the statement that no new patients should be prescribed Actos due to its dangerous side effects. While the EMA did not issue an Actos recall for the entire European Union, it confirmed that this particular Type 2 diabetes drug put its users at a much greater risk for developing severe side effects, including bladder cancer. New Zealand has now scheduled its own recall of Actos due to perceived risks including heart failure, heart attack, stroke and bladder cancer just like the drug’s predecessor, Avandia.
Germany and France based their recall of Actos on a French study indicating an increased risk of bladder cancer in those taking the drug. The study was done on over 150,000 study participants who had taken Actos between 2006 and 2009, with findings of a 22% increase in bladder cancer in those who took Actos to control their Type 2 diabetes. In those who were using higher dosages of Actos, that figure was as high as a 50% increased risk of bladder cancer.
In 2007 the FDA recalled Actos for improper warning labels, however once that issue was resolved they allowed the drug back on the market. At present the FDA continues to examine the results of a ten year study done on over a million patients who have regularly taken Actos. Although mid-point results from the study indicated a possibility of increased bladder cancer risk, the results were less than definitive, leading the FDA to allow Actos to remain on the market until further results are in.
Actos is routinely prescribed for Type 2 diabetes when it is not being well-controlled by diet and exercise alone. Actos is manufactured by Takeda Pharmaceuticals, a Japanese corporation, and co-marketed by Eli Lilly in the United States. Actos is Takeda’s best-selling drug, making them over $3.4 billion dollars in 2010 alone. The FDA approved Actos in 1999, and it quickly became the most prescribed alternative to Avandia which had been linked to stroke and heart attack. The FDA issued a black box warning to be placed on Actos labels in 2007 after it was determined that Actos could increase the risk of congestive heart failure. June, 2011 saw yet another revision to the Actos warning label which now clearly states to Actos patients that they face an increased risk of bladder cancer should they take the drug for longer than a year. This FDA warning also includes combination drugs such as ActoplusMet, ActoplusMet RX and Duetact. It is estimated that Actos lawsuits will lead to payments between one and five billion dollars on at least 13,000 lawsuits.
Takeda Pharmaceuticals will continue its ten-year observational cohort study which included nearly 200,000 patients. The interim analysis was done in 2008 among patients with a median duration of Actos therapy of two years, and a range of three months to eight and a half years. After adjustments were made for age, sex, use of tobacco products and use of other diabetes medications there appeared to be no significant increase in the risk for bladder cancer in those who had taken the medication for short amounts of time or in small dosages. Those who had taken Actos for more than twelve months, however, showed an almost 40% increase in bladder cancer risk. Other studies have shown similar risks in those taking higher dosages of Actos or taking it for longer periods of time. Some believe the FDA approves drugs too quickly and is not as concerned with possibly jeopardizing patient safety as other countries appear to be.
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.
Summary of the Ten-Year Study
The study the FDA is basing their opinions on was actually conducted by Takeda Pharmaceuticals, the manufacturer of Actos. Takeda simultaneously conducted case-control studies on patients with Type 2 diabetes who were also members of Kaiser Permanente Northern California health plan. The participants in these studies were over the age of forty at the onset of the study, and any patients who had been diagnosed with bladder cancer prior to the study were excluded.
The larger cohort study included over 190,000 patients and the median duration of the Actos therapy was two years, with a range of three months to eight and a half years. Once the study was adjusted for age, sex, use of tobacco products as well as the use of other diabetes drugs it showed no significant increase in bladder cancer risk for those simply “exposed” to Actos. On the contrary, the risk appeared to increase significantly in those taking the drug for longer than twelve months or in higher dosages—as much as a 40% increase in the risk of bladder cancer.
French National Health Insurance Plan Study
The FDA also took a passing look at another cohort study conducted by the French National Health Insurance Plan which included approximately a million and a half patients with Type 2 diabetes and lasted for four years. After the normal adjustments for age, sex, and the use of other anti-diabetic medications, the French study showed a significant increase in the risk for patients taking Actos to contract bladder cancer as compared to other anti-diabetic drugs. The French study correlated a cumulative dosage of more than 28,000 mg of Actos or exposures of longer than twelve months with a significantly elevated risk of bladder cancer.
FDA Concerned With More Than Consumer Safety?
There is some speculation that our FDA is a bit too cozy with huge drug companies and is perhaps more concerned with corporate profits than consumer safety. One non-profit consumer advocacy group known as Public Citizen has gone head to head with the FDA time after time, believing the agency is too slow to recall defective drugs or issue appropriate warnings. This belief stems from the fact that governmental agencies in other countries typically ban drugs believed to be harmful or at least issue appropriate warnings much sooner than the FDA does.
How the Warning Label has Changed
In 2002 the FDA required that the Actos label carry the warning that when combined with insulin a small number of patients with existing cardiac disease were found to develop congestive heart failure. In 2004, the warning label was changed to add carcinogenesis, mutagenesis and impairment of fertility to the list of precautions. On August 4, 2011, the FDA approved major changes to the warnings and precautions section of the Actos label to include the increased risk of bladder cancer, and cautioned doctors to refrain from prescribing Actos for those patients with a history of bladder cancer.
Patient Warnings for Actos
Physicians are advised to not only be cautious in prescribing Actos for those with a history of bladder cancer, but to be vigilant in issuing relevant warnings to their patients. Patients should be advised to contact a medical professional immediately if they experience any symptoms of bladder cancer including blood in the urine, pain while urinating, urination urgency or pain in the lower abdomen or back. Patients should additionally be encouraged to read the entire medication guide received with their prescription of Actos, and physicians must report any adverse events in their patients using Actos to the FDA.
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.
Summary of the Ten-Year Study
The study the FDA is basing their opinions on was actually conducted by Takeda Pharmaceuticals, the manufacturer of Actos. Takeda simultaneously conducted case-control studies on patients with Type 2 diabetes who were also members of Kaiser Permanente Northern California health plan. The participants in these studies were over the age of forty at the onset of the study, and any patients who had been diagnosed with bladder cancer prior to the study were excluded.
The larger cohort study included over 190,000 patients and the median duration of the Actos therapy was two years, with a range of three months to eight and a half years. Once the study was adjusted for age, sex, use of tobacco products as well as the use of other diabetes drugs it showed no significant increase in bladder cancer risk for those simply “exposed” to Actos. On the contrary, the risk appeared to increase significantly in those taking the drug for longer than twelve months or in higher dosages—as much as a 40% increase in the risk of bladder cancer.
French National Health Insurance Plan Study
The FDA also took a passing look at another cohort study conducted by the French National Health Insurance Plan which included approximately a million and a half patients with Type 2 diabetes and lasted for four years. After the normal adjustments for age, sex, and the use of other anti-diabetic medications, the French study showed a significant increase in the risk for patients taking Actos to contract bladder cancer as compared to other anti-diabetic drugs. The French study correlated a cumulative dosage of more than 28,000 mg of Actos or exposures of longer than twelve months with a significantly elevated risk of bladder cancer.
FDA Concerned With More Than Consumer Safety?
There is some speculation that our FDA is a bit too cozy with huge drug companies and is perhaps more concerned with corporate profits than consumer safety. One non-profit consumer advocacy group known as Public Citizen has gone head to head with the FDA time after time, believing the agency is too slow to recall defective drugs or issue appropriate warnings. This belief stems from the fact that governmental agencies in other countries typically ban drugs believed to be harmful or at least issue appropriate warnings much sooner than the FDA does.
How the Warning Label has Changed
In 2002 the FDA required that the Actos label carry the warning that when combined with insulin a small number of patients with existing cardiac disease were found to develop congestive heart failure. In 2004, the warning label was changed to add carcinogenesis, mutagenesis and impairment of fertility to the list of precautions. On August 4, 2011, the FDA approved major changes to the warnings and precautions section of the Actos label to include the increased risk of bladder cancer, and cautioned doctors to refrain from prescribing Actos for those patients with a history of bladder cancer.
Patient Warnings for Actos
Physicians are advised to not only be cautious in prescribing Actos for those with a history of bladder cancer, but to be vigilant in issuing relevant warnings to their patients. Patients should be advised to contact a medical professional immediately if they experience any symptoms of bladder cancer including blood in the urine, pain while urinating, urination urgency or pain in the lower abdomen or back. Patients should additionally be encouraged to read the entire medication guide received with their prescription of Actos, and physicians must report any adverse events in their patients using Actos to the FDA.
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.
Macular Edema
A study presented at the yearly meeting of the American Diabetes Association this past June found that those taking Actos have a three to six times increased risk of developing macular edema. Macular edema causes an eye disease in which the retina swells and thickens and can lead to permanent blindness. Diabetic eye disease is now the most common cause of blindness in those younger than age 65, and although the best way to avoid this particular side-effect of diabetes is by keeping your blood sugar under control, Actos appears to increase the risk of macular edema even though it does control the blood sugar.
Weight Gain
Weight gain also appears to be a side effect of Actos, however it must be noted that there is significant difference between a slow weight gain as the result of the drug and a rapid weight gain which could signal congestive heart failure. Rapid weight gain is any more than five pounds in a week, and should be a reason to consult your physicians immediately. On average, those taking Actos gained from two to six pounds over a period of four months to six months, while those patients not taking Actos lost about three pounds during the same time period.
In patients who were taking both Actos and insulin or other oral diabetes medications, the weight gain increased to between nine and ten pounds on average. Patients taking higher dosages of Actos gained larger amounts of weight than those taking lower doses, however those whose weight gain was related to fluid retention likely suffered more serious cardiovascular problems. Actos has been shown to worsen congestive heart failure or in some cases cause it. A primary initial symptom of congestive heart failure is an unexplained, quick weight gain, so it is important for those taking Actos to monitor their weight regularly.
Liver Disease
Patients who have shown signs of prior liver disease should not take Actos or any other drug in the thiazolidinedione class. These drugs have been definitively associated with significant elevations in liver enzymes, jaundice, liver failure and death due to liver failure. These liver problems have been seen both in long-term and short-term patient use of Actos. Any patients taking Actos should be aware of the potential liver problems, and should report any unexplained nausea, vomiting, fatigue, dark urine or abdominal pain to their physician immediately. If jaundice develops the medication should be immediately discontinued. Those taking Actos who show even a moderate increase in liver enzymes should continue the drug only with their physician’s approval, and with great caution. If Actos use has led to a seriously impaired liver, a liver transplant may be necessary. Conversely, while Actos has been shown to potentially cause liver enzymes to increase to serious levels, there is medical evidence which shows Actos may actually provide beneficial effects in treating fatty liver disease. Several studies have shown that Actos can reduce the liver fats by half in less than half a year.
Other Serious Side Effects
Actos has also been known to cause allergic reactions, blurry vision, easy bruising or bleeding, flu-like symptoms, muscle pain and serious tooth pain and problems. Actos is contraindicated in those who are scheduled for an upcoming surgery or have any type of known allergy to foods, dyes or preservatives. Women who are pregnant or thinking of becoming pregnant, or those who are breastfeeding should not take Actos as it is considered a Pregnancy Category C drug meaning it is not considered safe to take when pregnancy is a possibility. Actos can also pass into breast milk, so should definitely not be taken by women who are currently breastfeeding. Actos can also potentially interact with other prescription drugs as well as non-prescription medications, vitamins and herbal supplements, so it is important that your doctor be aware of everything you take regularly. While bladder cancer and cardiovascular problems are the most serious of the known side effects of Actos, the side effects listed above can also have potentially serious consequences.
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.
Macular Edema
A study presented at the yearly meeting of the American Diabetes Association this past June found that those taking Actos have a three to six times increased risk of developing macular edema. Macular edema causes an eye disease in which the retina swells and thickens and can lead to permanent blindness. Diabetic eye disease is now the most common cause of blindness in those younger than age 65, and although the best way to avoid this particular side-effect of diabetes is by keeping your blood sugar under control, Actos appears to increase the risk of macular edema even though it does control the blood sugar.
Weight Gain
Weight gain also appears to be a side effect of Actos, however it must be noted that there is significant difference between a slow weight gain as the result of the drug and a rapid weight gain which could signal congestive heart failure. Rapid weight gain is any more than five pounds in a week, and should be a reason to consult your physicians immediately. On average, those taking Actos gained from two to six pounds over a period of four months to six months, while those patients not taking Actos lost about three pounds during the same time period.
In patients who were taking both Actos and insulin or other oral diabetes medications, the weight gain increased to between nine and ten pounds on average. Patients taking higher dosages of Actos gained larger amounts of weight than those taking lower doses, however those whose weight gain was related to fluid retention likely suffered more serious cardiovascular problems. Actos has been shown to worsen congestive heart failure or in some cases cause it. A primary initial symptom of congestive heart failure is an unexplained, quick weight gain, so it is important for those taking Actos to monitor their weight regularly.
Liver Disease
Patients who have shown signs of prior liver disease should not take Actos or any other drug in the thiazolidinedione class. These drugs have been definitively associated with significant elevations in liver enzymes, jaundice, liver failure and death due to liver failure. These liver problems have been seen both in long-term and short-term patient use of Actos. Any patients taking Actos should be aware of the potential liver problems, and should report any unexplained nausea, vomiting, fatigue, dark urine or abdominal pain to their physician immediately. If jaundice develops the medication should be immediately discontinued. Those taking Actos who show even a moderate increase in liver enzymes should continue the drug only with their physician’s approval, and with great caution. If Actos use has led to a seriously impaired liver, a liver transplant may be necessary. Conversely, while Actos has been shown to potentially cause liver enzymes to increase to serious levels, there is medical evidence which shows Actos may actually provide beneficial effects in treating fatty liver disease. Several studies have shown that Actos can reduce the liver fats by half in less than half a year.
Other Serious Side Effects
Actos has also been known to cause allergic reactions, blurry vision, easy bruising or bleeding, flu-like symptoms, muscle pain and serious tooth pain and problems. Actos is contraindicated in those who are scheduled for an upcoming surgery or have any type of known allergy to foods, dyes or preservatives. Women who are pregnant or thinking of becoming pregnant, or those who are breastfeeding should not take Actos as it is considered a Pregnancy Category C drug meaning it is not considered safe to take when pregnancy is a possibility. Actos can also pass into breast milk, so should definitely not be taken by women who are currently breastfeeding. Actos can also potentially interact with other prescription drugs as well as non-prescription medications, vitamins and herbal supplements, so it is important that your doctor be aware of everything you take regularly. While bladder cancer and cardiovascular problems are the most serious of the known side effects of Actos, the side effects listed above can also have potentially serious consequences.
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 Pioglitazone
Pre-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.
Results of Safety Review
Although the results of the FDA-ordered safety review of pioglitazone were less than positively conclusive, the French Agency for the Safety of Health Products nonetheless pulled Actos from the French market this June due to health concerns. France conducted their own safety study, using over 1.5 million diabetic patients who were currently being treated with the drug—a study which more definitively showed a positive correlation between bladder cancer and pioglitazone. This study also pointed to the fact that the risk increases in patients who take the drug for a longer time period than one year. Following on the heels of the French decision, the German Federal Institute for Drugs and Medical Devices advised doctors against prescribing Actos, based on the French study results. As of September, 2011, no other countries have pulled the drug due to safety concerns.
Specific Issues Related to Safety Reviews
The FDA believes the risk of bladder cancer rises following an increase in dosage or use of longer than a year, citing a 40% increased risk in those who fell in these categories. Because the elderly are already more susceptible to bladder cancer an alternative diabetic drug should be used in older patients. The FDA further asserted that doctors should use extreme caution and full assessments when prescribing Actos, avoiding using the drug on those with active bladder cancer or those with a history of this type of cancer. Expect continued updates on the safety of Actos as further studies are concluded.
Clinical Studies of Pioglitazone
Pre-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.
Results of Safety Review
Although the results of the FDA-ordered safety review of pioglitazone were less than positively conclusive, the French Agency for the Safety of Health Products nonetheless pulled Actos from the French market this June due to health concerns. France conducted their own safety study, using over 1.5 million diabetic patients who were currently being treated with the drug—a study which more definitively showed a positive correlation between bladder cancer and pioglitazone. This study also pointed to the fact that the risk increases in patients who take the drug for a longer time period than one year. Following on the heels of the French decision, the German Federal Institute for Drugs and Medical Devices advised doctors against prescribing Actos, based on the French study results. As of September, 2011, no other countries have pulled the drug due to safety concerns.
Specific Issues Related to Safety Reviews
The FDA believes the risk of bladder cancer rises following an increase in dosage or use of longer than a year, citing a 40% increased risk in those who fell in these categories. Because the elderly are already more susceptible to bladder cancer an alternative diabetic drug should be used in older patients. The FDA further asserted that doctors should use extreme caution and full assessments when prescribing Actos, avoiding using the drug on those with active bladder cancer or those with a history of this type of cancer. Expect continued updates on the safety of Actos as further studies are concluded.
Pioglitazone Receives New Warnings Due to Slight Increase in Bladder Cancer Risk
The 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 Patients
Physicians 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 Information
In 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.
Further Research Indicated
The CHMP has indicated that further research and controlled studies are necessary to fully explore the risk of bladder cancer in those taking pioglitazone as compared to those who take other diabetic drugs or those who take no diabetic drugs. It is expected that the issue of whether prolonged use or high cumulative doses are more likely to cause bladder cancer will be more clearly addressed in subsequent studies.
The Bottom Line
Both the SAG and CHMP agree that among patients who will not receive adequate treatment from other diabetic drugs—and who are neither elderly nor have a history of bladder cancer—pioglitazone is still considered the best therapy. While patients must be carefully screened and monitored, the benefits of pioglitazone still outweigh the potential risks.
Assessing Risk Factors in Potential Patients
Physicians 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 Information
In 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.
Further Research Indicated
The CHMP has indicated that further research and controlled studies are necessary to fully explore the risk of bladder cancer in those taking pioglitazone as compared to those who take other diabetic drugs or those who take no diabetic drugs. It is expected that the issue of whether prolonged use or high cumulative doses are more likely to cause bladder cancer will be more clearly addressed in subsequent studies.
The Bottom Line
Both the SAG and CHMP agree that among patients who will not receive adequate treatment from other diabetic drugs—and who are neither elderly nor have a history of bladder cancer—pioglitazone is still considered the best therapy. While patients must be carefully screened and monitored, the benefits of pioglitazone still outweigh the potential 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 New
As 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.
Letters Issued to Health Care Professionals Prescribing Actos
At the same time the FDA asked for better warning labels, they requested that any letters sent to health care professionals regarding safety concerns of Actos also be sent to the NDA and FDA. Actos is prescribed for Type 2 diabetes, along with a nutritious diet and regular exercise, and is also found in a combination drug with Metformin to control the amount of sugar in the blood and help the body use insulin normally.
Recent Health Reviews
While the more recent health reviews of Actos have led to France and Germany pulling the drug from the market, the fnial recommendations state that Actos continues to offer significant benefits in carefully screened patients. Actos should not be used in those with a history of bladder cancer or in the elderly population, and those taking the drug should be monitored carefully, and kept at the lowest effective dosage.
Warnings are Not New
As 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.
Letters Issued to Health Care Professionals Prescribing Actos
At the same time the FDA asked for better warning labels, they requested that any letters sent to health care professionals regarding safety concerns of Actos also be sent to the NDA and FDA. Actos is prescribed for Type 2 diabetes, along with a nutritious diet and regular exercise, and is also found in a combination drug with Metformin to control the amount of sugar in the blood and help the body use insulin normally.
Recent Health Reviews
While the more recent health reviews of Actos have led to France and Germany pulling the drug from the market, the fnial recommendations state that Actos continues to offer significant benefits in carefully screened patients. Actos should not be used in those with a history of bladder cancer or in the elderly population, and those taking the drug should be monitored carefully, and kept at the lowest effective dosage.
FDA Issues Sterner Warnings to Manufacturers of Diabetic Drug Actos
Although 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 Required
In 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 Actos
The 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 Information
The 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.
FDA Postmarketing Requirements
In the same letter to Takeda, the FDA offered specific postmarketing requirements which included directing Takeda Pharmaceuticals to continue and modify their ten-year study which assessed the related risk of bladder cancer in those taking Actos. The Final Protocol Amendment Submission must be submitted to the FDA by December 16, 2011, the 4th Interim Report Submission by June 30, 2012, the Study Completion by December 31, 2012, and the Final Report Submission by December 31, 2013. Takeda is asked to report periodically on studies and trials conducted on Actos however the Risk Evaluation and Mitigation Strategy Requirements submitted were approved with no further changes required.
Postapproval Clinical Trial
The FDA directs Takeda to include the status of any postapproval clinical trials, including when the enrollment began, how many patients were enrolled, the date of expected completion, and any difficulties encountered in the trial. Generic products for the drug Actos must have a REMS, supporting documents and appended documents prior to marketing the product.
As a final admonishment to Takeda, the FDA warns that all promotional materials and package inserts for the drug Actos as well as other drugs containing pioglitazone be submitted at the time of publication, and that all promotional materials must be revised to be consistent with mandated label changes.
Drugs Included, Safety Updates Required
In 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 Actos
The 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 Information
The 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.
FDA Postmarketing Requirements
In the same letter to Takeda, the FDA offered specific postmarketing requirements which included directing Takeda Pharmaceuticals to continue and modify their ten-year study which assessed the related risk of bladder cancer in those taking Actos. The Final Protocol Amendment Submission must be submitted to the FDA by December 16, 2011, the 4th Interim Report Submission by June 30, 2012, the Study Completion by December 31, 2012, and the Final Report Submission by December 31, 2013. Takeda is asked to report periodically on studies and trials conducted on Actos however the Risk Evaluation and Mitigation Strategy Requirements submitted were approved with no further changes required.
Postapproval Clinical Trial
The FDA directs Takeda to include the status of any postapproval clinical trials, including when the enrollment began, how many patients were enrolled, the date of expected completion, and any difficulties encountered in the trial. Generic products for the drug Actos must have a REMS, supporting documents and appended documents prior to marketing the product.
As a final admonishment to Takeda, the FDA warns that all promotional materials and package inserts for the drug Actos as well as other drugs containing pioglitazone be submitted at the time of publication, and that all promotional materials must be revised to be consistent with mandated label changes.
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