Depakote is a prescription drug used to treat epileptic seizures, psychological disorders such as bipolar disorder, and migraine headaches. Depakote is marketed under several brand names and generic versions of the drug, including Depakote ER, Depakote Sprinkles, Depakene, and Valproate.
Research studies strongly indicate that women who take Depakote during pregnancy are at a substantially greater risk for having children born with birth defects. One of the most severe and disabling of these defects is spina bifida. Spina bifida causes incomplete development of the bones of the spine, leading to protrusion of the spinal cord and fluid through a gap in the bones. Other birth defects associated with Depakote are malformed head and facial structures including cleft palate, anencephaly, which causes a baby to be born without a brain, and fetal death.
Additional research has shown that children born to mothers who took Depakote during pregnancy are more likely to have cognitive defects resulting in lower IQ test scores. In response to this research, the Food and Drug Administration (FDA) recently issued a Safety Communication to inform the public about the increased risk from Depakote of children with lower cognitive test scores compared to children born to mothers taking a different anti-seizure drug. The FDA warns of the risk of these and other birth defects associated with Depakote, and recommends that doctors counsel their patients about these risks.
Physicians have been guided by the research results in caring for their patients. It is now common medical practice for doctors to advise women who intend to become pregnant to immediately stop taking Depakote if possible because of the risk of birth defects. Women who are concerned about the risks of taking Depakote should consult with a qualified healthcare professional.
Litigation connected with Depakote and birth defects is ongoing. A class action lawsuit is dealing with allegations that Abbott Laboratories, the Depakote drug manufacturer, may have intentionally failed to provide warnings of birth defect risks in the drug labeling. Women continued to take Depakote during pregnancy in the absence of such a warning, allegedly resulting in their children suffering from birth defects.
If you think that your child may have suffered a birth defect related to taking Depakote during pregnancy, you have rights. It is important that you retain all pertinent medical records and bills to help you obtain any compensation to which you may be entitled. It is also important for you to speak with a qualified drug injury attorney about your rights and your potential for any compensation that may be due to you and your family.
Product Defects, Accident and Injury law, Criminal Defense, Traffic Tickets, Family Law at Sullo & Sullo, LLP!
Showing posts with label actos recall 2010. Show all posts
Showing posts with label actos recall 2010. Show all posts
Actos Discussions Part 1: Your Actos Case
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.
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.
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® 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 Myocardial Infarction
After a Journal of American Medical Association publication of a meta-analysis suggested that long-term use of the diabetes drug Avandia was associated with an increased risk of myocardial infarction, the maker of Avandia, GlaxoSmithKline, declared there was little difference in the safety profile of their drug, Avandia and the “other” drug for Type 2 diabetes, Takeda Pharmaceutical’s Actos. Further studies however have not completely backed up that declaration. In nineteen separate controlled trials, involving over 16,000 patients, the end results demonstrated that while 4.4 percent of the patients who received Actos underwent myocardial infarction or stroke 5.7 percent of patients receiving control therapy suffered a myocardial infarction.
In the same studies, serious heart failure was reported in 2.3 percent of those taking Actos, while only occurring in 1.8 percent of those in the control group. The author of the results of the studies, Michael Lincoff, stated that not only does Actos—also known as pioglitazone—not appear to have the same level of detrimental effects as Avandia, but it could potentially have a protective effect on the heart. Takeda Pharmaceuticals, currently struggling under the rash of lawsuits filed against them due to evidence that Actos may significantly increase the risk of bladder cancer, does not believe their drug is responsible for episodes of myocardial infarction, or heart attack.
Other studies are not so quick to absolve Takeda Pharmaceuticals from their drug’s responsibility to potentially cause myocardial infarction, and the FDA has mandated that all those who take Actos be thoroughly warned about the possibility that it could bring about a serious or fatal heart attack. Actos is Takeda’s primary drug, accounting for over 15% of all new prescriptions in the United States. Type 2 diabetes affects as many as twenty million Americans, and is characterized by the body’s inability to respond to insulin as it should. When Type 2 diabetes is left untreated, it can lead to a myriad of other health problems, including cardiovascular disease.
Another study done in 2007 revealed little significant differences between Actos and Avandia as far as the increase in risk of myocardial infarction. At least twelve specific cases have indicated a direct correlation between Actos and myocardial infarction. The age of the patients ranged from 50 to mid-80’s, and were reported in 2009 and 2010 by their physicians who believe their deaths were a direct result of taking Actos. Although the current studies may show little agreement as to whether Actos can directly cause myocardial infarction, the fact that the FDA requires Takeda to list myocardial infarction as a potential serious side effect should definitely make those taking the drug consider alternative therapies. Especially for patients with a history of cardiovascular risks, taking Actos could cause a worsening of those risks along with a possible increased risk of bladder cancer.
Germany, France and New Zealand all believe that the risks of Actos far outweigh the benefits and have subsequently removed them from use. The FDA is reserving final determination on the risks of Actos until further studies have been conducted, and although they require a black box warning on the drug, it will remain on the shelves—at least for now.
In the same studies, serious heart failure was reported in 2.3 percent of those taking Actos, while only occurring in 1.8 percent of those in the control group. The author of the results of the studies, Michael Lincoff, stated that not only does Actos—also known as pioglitazone—not appear to have the same level of detrimental effects as Avandia, but it could potentially have a protective effect on the heart. Takeda Pharmaceuticals, currently struggling under the rash of lawsuits filed against them due to evidence that Actos may significantly increase the risk of bladder cancer, does not believe their drug is responsible for episodes of myocardial infarction, or heart attack.
Other studies are not so quick to absolve Takeda Pharmaceuticals from their drug’s responsibility to potentially cause myocardial infarction, and the FDA has mandated that all those who take Actos be thoroughly warned about the possibility that it could bring about a serious or fatal heart attack. Actos is Takeda’s primary drug, accounting for over 15% of all new prescriptions in the United States. Type 2 diabetes affects as many as twenty million Americans, and is characterized by the body’s inability to respond to insulin as it should. When Type 2 diabetes is left untreated, it can lead to a myriad of other health problems, including cardiovascular disease.
Another study done in 2007 revealed little significant differences between Actos and Avandia as far as the increase in risk of myocardial infarction. At least twelve specific cases have indicated a direct correlation between Actos and myocardial infarction. The age of the patients ranged from 50 to mid-80’s, and were reported in 2009 and 2010 by their physicians who believe their deaths were a direct result of taking Actos. Although the current studies may show little agreement as to whether Actos can directly cause myocardial infarction, the fact that the FDA requires Takeda to list myocardial infarction as a potential serious side effect should definitely make those taking the drug consider alternative therapies. Especially for patients with a history of cardiovascular risks, taking Actos could cause a worsening of those risks along with a possible increased risk of bladder cancer.
Germany, France and New Zealand all believe that the risks of Actos far outweigh the benefits and have subsequently removed them from use. The FDA is reserving final determination on the risks of Actos until further studies have been conducted, and although they require a black box warning on the drug, it will remain on the shelves—at least for now.
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® 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.
European Medicines Agency Scientific Studies on Pioglitazone
The European Medicines Agency released a scientific study on the benefits and risks of the drug pioglitazone, also known as Actos, in January of 2007. This drug is currently used as a single treatment for Type 2 diabetes or in a dual combination form with metformin or sulphonylurea. When used alone, pioglitazone is typically used as therapy for the overweight patient whose Type 2 diabetes is not being controlled through diet and exercise and for whom the drug metformin is inappropriate. The combination drug is most often used in those patients who have insufficient glycemic control despite taking metformin alone or for those patients who have shown a level of intolerance to metformin. The results of the study showed that when pioglitazone was prescribed in conjunction with other anti-diabetic therapies such as insulin, the risk of macrovascular disease was greatly reduced. Macrovascular disease is common in those with long-term diabetes and refers to a disease of the large blood vessels in the body.
Clinical Support for Pioglitazone Application
Evidence was submitted which supported the application of pioglitazone, including four clinical trial reports which studied the safety of the drug when used in conjunction with insulin therapy. The studies were conducted according to prevailing ethical standards, and were random, double-blind, placebo controlled.
First Pioglitazone Study—PNFP-014
Pioglitazone was administered both in 15 mg dosages as well as 30 mg dosages in combination with insulin then compared with using insulin therapy alone. Participants in the studies were between the ages of 30 and 75, and had been on a fixed dose of insulin for at least a month prior to beginning the study. The mean baseline age was 57 years, with an average BMI of 33.6. Nearly 3/4ths of the participants in the study were Caucasian, with slightly more than half being female. Although the baseline systolic blood pressure was minimally higher in the group receiving pioglitazone plus insulin as opposed to the group receiving insulin alone, there were no other baseline variables involved. The patients who received both pioglitazone and insulin showed statistical decreases in the HbA1c levels which measure the average amount of sugar in the blood over a period of three months, and is different from glucose measurements. The HbA1c levels essentially give the physician an indication of how well the diabetes is being controlled.
Second Pioglitazone Study—PNFP-343
The second study compared doses of pioglitazone using 30 mg and 45 mg and was tested on subjects whose Type 2 diabetes was poorly controlled with insulin therapy alone. Participants were at least 18 years old, and had HbA1c values greater than 8%--any value over 6% indicates diabetes which is poorly controlled. The variables in this study were the HbA1c levels and the serum lipids which included total cholesterol, triglycerides, HDL, LDL and VLDL cholesterol and free fatty acids. The mean age was 56.5 and the mean BMI was 33.19, with 63% of the participants being Caucasian, and slightly more than half being male. The mean insulin dose was 69.2 units per day, and over one-fourth of the people in the study stated they also used other forms of anti-diabetic therapies in addition to insulin. The results of the study showed significant reduction in the use of insulin among the groups receiving both strengths of the drug, although there was a greater reduction in those using the 45 mg. tablets.
Third Pioglitazone Study—GLAT
The third study tested the safety and efficiency of the 30 mg. tablet of pioglitazone plus insulin as compared to insulin alone. The participants ranged in age from 30-70 years old who had HbA1c levels higher than 7.5% and were had taking insulin therapy for at least three months. The duration of this study was up to one year, and the variables included baseline HbA1c, Fasting serum levels, fasting serum lipids, FFA levels, urinary albumin/creatinine ratios, c-reactive protein levels, insulin dosage and rate of hypoglycemia. The mean age of the participants was 58.9 years, with a mean BMI of 32.1. The vast majority—96.4% were Caucasian, and the mean duration of the diabetes was 13.5 years. The HbA1c levels averaged 8.8%, which suggested the study population had very poorly controlled diabetes overall. After six months in the trial, those taking the pioglitazone had reduced their HbA1c levels by an average of .69%, while the placebo group had only reached an average of .14 %. The group taking pioglitazone was also able to reduce their insulin use by an average of 11.4 units per day. Read more ....
Clinical Support for Pioglitazone Application
Evidence was submitted which supported the application of pioglitazone, including four clinical trial reports which studied the safety of the drug when used in conjunction with insulin therapy. The studies were conducted according to prevailing ethical standards, and were random, double-blind, placebo controlled.
First Pioglitazone Study—PNFP-014
Pioglitazone was administered both in 15 mg dosages as well as 30 mg dosages in combination with insulin then compared with using insulin therapy alone. Participants in the studies were between the ages of 30 and 75, and had been on a fixed dose of insulin for at least a month prior to beginning the study. The mean baseline age was 57 years, with an average BMI of 33.6. Nearly 3/4ths of the participants in the study were Caucasian, with slightly more than half being female. Although the baseline systolic blood pressure was minimally higher in the group receiving pioglitazone plus insulin as opposed to the group receiving insulin alone, there were no other baseline variables involved. The patients who received both pioglitazone and insulin showed statistical decreases in the HbA1c levels which measure the average amount of sugar in the blood over a period of three months, and is different from glucose measurements. The HbA1c levels essentially give the physician an indication of how well the diabetes is being controlled.
Second Pioglitazone Study—PNFP-343
The second study compared doses of pioglitazone using 30 mg and 45 mg and was tested on subjects whose Type 2 diabetes was poorly controlled with insulin therapy alone. Participants were at least 18 years old, and had HbA1c values greater than 8%--any value over 6% indicates diabetes which is poorly controlled. The variables in this study were the HbA1c levels and the serum lipids which included total cholesterol, triglycerides, HDL, LDL and VLDL cholesterol and free fatty acids. The mean age was 56.5 and the mean BMI was 33.19, with 63% of the participants being Caucasian, and slightly more than half being male. The mean insulin dose was 69.2 units per day, and over one-fourth of the people in the study stated they also used other forms of anti-diabetic therapies in addition to insulin. The results of the study showed significant reduction in the use of insulin among the groups receiving both strengths of the drug, although there was a greater reduction in those using the 45 mg. tablets.
Third Pioglitazone Study—GLAT
The third study tested the safety and efficiency of the 30 mg. tablet of pioglitazone plus insulin as compared to insulin alone. The participants ranged in age from 30-70 years old who had HbA1c levels higher than 7.5% and were had taking insulin therapy for at least three months. The duration of this study was up to one year, and the variables included baseline HbA1c, Fasting serum levels, fasting serum lipids, FFA levels, urinary albumin/creatinine ratios, c-reactive protein levels, insulin dosage and rate of hypoglycemia. The mean age of the participants was 58.9 years, with a mean BMI of 32.1. The vast majority—96.4% were Caucasian, and the mean duration of the diabetes was 13.5 years. The HbA1c levels averaged 8.8%, which suggested the study population had very poorly controlled diabetes overall. After six months in the trial, those taking the pioglitazone had reduced their HbA1c levels by an average of .69%, while the placebo group had only reached an average of .14 %. The group taking pioglitazone was also able to reduce their insulin use by an average of 11.4 units per day. Read more ....
FDA Approves Cancer Warning for Diabetic Drug Actos
The blockbuster drug, Actos, which is prescribed to control Type 2 diabetes, has received new warning language on the label regarding a potential risk of bladder cancer for those taking the drug. Actos, also known as pioglitazone, is manufactured by Takeda Pharmaceuticals, a Japanese-based company, and is currently their best-selling drug, with sales of $3.4 billion last year alone. Sales of Actos had shown a significant upswing due to the fact that its primary competitor—Avandia—has been linked to a higher risk of heart attack and even death. The updated label warnings came on the heels of an EMA safety review of the drug as well as a ten-year study conducted by Takeda. The Takeda study indicated a statistically significant increase in the risk of bladder cancer for those taking the drug for longer than two years.
Other Drugs Containing Pioglitazone
Other than Actos, the drugs ActoPlus Met, ActoPlus Met XR and Duetact will all carry the same warnings due to containing pioglitazone as an active ingredient. All of these drugs are used to treat Type 2 diabetes, to increase sensitivity to insulin and effectively control blood sugar levels. A combination drug containing metformin and pioglitazone is used for the same purpose, although all these drugs are expected to be used in conjunction with a healthy diet and sensible exercise program.
France and Germany Weigh In
Just this past June, both France and Germany issued recalls of Actos following a public insurance data review which showed a fairly strong correlation between pioglitazone and bladder cancer risk. Suggestions from the EMA study related primarily to including more cautionary warnings on the labels of the drug as well as a six-month review of each patient taking Actos.
Additional Cautions
Additionally, the EMA advised physicians to practice more appropriate patient selections as well as exclusions for specific groups when considering the drug. Specifically, those patients who have bladder cancer or have had the disease in the past should be prescribed an alternative drug as should the elderly. All patients who take Actos should have regular checkups and appropriate medical tests performed regularly to address safety concerns.
First Lawsuit Filed
A California man who developed an aggressive form of bladder cancer after taking the drug for two years has filed the first lawsuit against Takeda, however it is expected that many more complaints are forthcoming. Throughout the United States Actos lawyers will be investigating and evaluating potential cases for those who feel their health was negatively impacted through the use of Actos.
Other Drugs Containing Pioglitazone
Other than Actos, the drugs ActoPlus Met, ActoPlus Met XR and Duetact will all carry the same warnings due to containing pioglitazone as an active ingredient. All of these drugs are used to treat Type 2 diabetes, to increase sensitivity to insulin and effectively control blood sugar levels. A combination drug containing metformin and pioglitazone is used for the same purpose, although all these drugs are expected to be used in conjunction with a healthy diet and sensible exercise program.
France and Germany Weigh In
Just this past June, both France and Germany issued recalls of Actos following a public insurance data review which showed a fairly strong correlation between pioglitazone and bladder cancer risk. Suggestions from the EMA study related primarily to including more cautionary warnings on the labels of the drug as well as a six-month review of each patient taking Actos.
Additional Cautions
Additionally, the EMA advised physicians to practice more appropriate patient selections as well as exclusions for specific groups when considering the drug. Specifically, those patients who have bladder cancer or have had the disease in the past should be prescribed an alternative drug as should the elderly. All patients who take Actos should have regular checkups and appropriate medical tests performed regularly to address safety concerns.
First Lawsuit Filed
A California man who developed an aggressive form of bladder cancer after taking the drug for two years has filed the first lawsuit against Takeda, however it is expected that many more complaints are forthcoming. Throughout the United States Actos lawyers will be investigating and evaluating potential cases for those who feel their health was negatively impacted through the use of Actos.
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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