Actos (pioglitazone), manufactured by Takeda Pharmaceuticals and distributed by Eli Lilly and Company, has been under FDA review since September 2010. In June 2011, the FDA issued a warning for Actos, while at the same time drug regulators in France and Germany suspended use of the drug, after it was linked to an increased risk for the development of bladder cancer. Following its review, the U.S. Food and Drug Administration (FDA) approved updated warning labels for Actos, a prescription medication used to treat Type 2 diabetes. The updated label states that Actos usage for more than one year may cause bladder cancer. The FDA reported in its data summary that “the risk of bladder cancer increased with increasing dose and duration of Actos use, reaching statistical significance after 24 months of exposure.” Actos quickly became one of the top-selling drugs in the United States after it received FDA approval in July 1999. However, in June 2011, the FDA warned that patients taking Actos for one year or longer were exposed to a risk of bladder cancer 40 percent higher than those who hadn’t taken the drug and ordered Takeda to include a warning about the increased risk of bladder cancer on the drug’s labeling. Most recently, a Canadian study led by Montreal epidemiologist Dr. Laurent Azoulay and published online in the British Medical Journal found that patients who take Actos two years or longer are twice as likely to develop bladder cancer as those who have never used the drug.
AndroGel 1% and AndroGel 1.62%
AndroGel 1% and AndroGel 1.62% are both prescription products used for daily testosterone replacement therapy (TRT). They are manufactured by Abbott Laboratories. The gel is applied to the skin of the shoulders and upper arms. AndroGel 1% may also be applied to the abdomen. Secondary exposure to testosterone in children and women can occur with the use of testosterone gel in men. Reported cases involved children ranging in age from 9 months to 7 years old. Physicians should advise patients of the reported signs and symptoms of secondary exposure, which may include the following: • In children: unexpected sexual development including inappropriate enlargement of the penis or clitoris, premature development of pubic hair, increased erections, aggressive behavior and advanced bone age. • In women: changes in hair distribution, increase in acne, or other signs of testosterone effects. In most cases, signs and symptoms of testosterone exposure regressed with the removal of the testosterone gel exposure. However, there were cases where enlarged genitalia did not fully return to age appropriate normal size, and bone age remained modestly greater than chronological age. AndroGel 1% was approved by the FDA in February 2000. In 2007, 1.4 million prescriptions for AndroGel 1% – the most commonly dispensed gel form of testosterone – were dispensed by U.S. retail pharmacies. Approximately 25,000 of those were dispensed for off-label use in women. In May 2009, the FDA announced it would required AndroGel 1 % to carry a boxed warning of adverse effects in children who were inadvertently exposed to testosterone through contact with another person being treated with these products. The FDA placed a Black Box warning about the risks of AndroGel 1% to children and women in September 2009. Androgel 1.62% was approved by the FDA in April 2011, and included the black box warning about secondary testosterone exposure for children and women. Secondary exposure to testosterone in children and women can occur with the use of testosterone gel in men. Cases of secondary exposure to testosterone have been reported in children. The area where the gel was applied should be covered, and patients are warned that others should not come into contact with the skin where the gel was applied. In at least one reported case of secondary exposure to testosterone in children, the reporter considered the possibility of secondary exposure from items such as the testosterone gel user’s shirt and other fabrics such as towels and sheets. The possibility of secondary exposure to testosterone gel should be brought to the attention of a health care provider
Manufactured by GlaxoSmithKline, Zofran (ondansetron) was approved to treat nausea during chemotherapy and following surgery. Zofran (ondansetron) works by blocking serotonin in the areas of the brain that trigger nausea and vomiting. Between 2002 and 2004, GSK began promoting Zofran off-label for the treatment of morning sickness during pregnancy, despite the fact the drug has not been approved for pregnant women and there have been no well controlled studies in pregnant women. The FDA has received nearly 500 reports of birth defects linked to Zofran. Birth defect risks include cleft palate and septal heart defects.
Approved in March 2013, Invokana (canagliflozin) is an SGLT2 Inhibitor used to treat adults with Type 2 diabetes, manufactured by Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson. SGLT2 inhibitors work by preventing high blood sugar by helping the patient’s kidneys remove excess sugar through their urine. In May 2015, the U.S.
Food and Drug Administration (FDA) issued a warning the drug has been lined to cases of ketoacidosis, a serious condition where there is too much acid in the blood. Complications of diabetic ketoacidosis include difficulty breathing, nausea/vomiting, abdominal pain, confusion and unusual fatigue or sleepiness. The condition can lead to diabetic coma and/or death.
Lawsuits filed against Johnson & Johnson subsidiary Janssen Pharmaceuticals and Bayer Corp. over the blood thinner Xarelto have been consolidated in Louisiana federal court. Xarelto has been linked to serious side effects including internal bleeding, gastrointestinal bleeding, brain bleed and death.
The Xarelto lawsuits come on the heels of the recent $650 million Pradaxa settlement. Researchers linked Pradaxa, also a blood thinning medication, to more than 500 deaths. Xarelto blood thinner litigation has been consolidated before U.S. District Judge Eldon Fallon in the Eastern District of Louisiana, who presided over suits against Merck & Co over its medication Vioxx. The Vioxx litigation resulted in a $4.85 billion settlement in 2007.
Xarelto is approved by the U.S. Food and Drug Administration (FDA) for six indications including reducing the risk of stroke in patients with nonvalvular atrial fibrillation; treating deep vein thrombosis and pulmonary embolism, and reducing the reoccurrence of these conditions; and preventing blood clots in patients following knee or hip replacement surgery.
Xarelto already carries a black box warning for an increased risk of blood clots with premature discontinuation of therapy, and a risk of epidural or spinal hematomas resulting in long-term or permanent paralysis in patients treated with Xarelto receiving neuraxial anesthesia or undergoing spinal puncture. Black box warnings are the most serious type of warning issued by the FDA, and indicate drugs that carry a significant risk of serious or life-threatening adverse effects
Testosterone Replacement Therapy (TRT) products for men have been linked to an increased risk of death, heart attack and stroke. Researchers found men who used testosterone therapy were 30 percent more likely to have a heart attack, stroke, or die after three years of use.
Furthermore, men who started the study with clear, unobstructed coronary arteries were just as likely to have a heart attack, stroke or die as men who entered the study with established coronary artery disease.
Testosterone therapy, such as the prescription topical treatments Androgel, Testim and Axiron, are used to help boost testosterone levels in men who have a deficiency of the male hormone. Symptoms of low testosterone include decreased libido and low energy.
Byetta and Januvia are two drugs used to treat Type 2 diabetes. The FDA approved Byetta in 2005 and Januvia in 2006. These drugs have been prescribed to millions of people in the United States. Since approving the medications, the FDA has issued several warnings about links between Byetta and Januvia to complications related to pancreatic diseases. Recent studies have linked these two drugs to acute pancreatitis and pancreatic cancer. We are currently investigating claims of pancreatic cancer
Lipitor, a statin drug to treat high cholesterol, was approved by the FDA, in 1996 and is one the best-selling prescription medications in the world. Recent studies have found a possible link between Lipitor and the risk of developing Type 2 diabetes. A University of Massachusetts study found a potential link in postmenopausal women, particularly those who had a Body Mass Index (BMI) less than 25. Of the 153,840 women evaluated, more than 10,000 had developed Type 2 diabetes by the end of the study
Approved by the FDA in October 2010, Pradaxa (Dabigatran) is marketed by Boehringer Ingelheim Pharmaceuticals, Inc., to reduce the risk of strokes and blood clots in people who have atrial fibrillation, a common heart rhythm abnormality. Pradaxa is in a class of anticoagulant medications known as “blood thinners.”
Pradaxa is a direct thrombin inhibitor. It prevents the formation of blood clots by counteracting the effects of thrombin, which is responsible for clotting. Boehringer Ingelheim Pharmaceuticals markets Pradaxa as the preferred blood thinner. It became the first alternative to warfarin for this indication.
According to Boehringer, it is easier to dose, requires less monitoring, and is more effective at preventing clots compared to warfarin (Coumadin). However, unlike warfarin, Pradaxa’s anticoagulation effect cannot be reversed with vitamin K, significantly increasing the odds that a bleeding event will turn fatal.
To date, there have been significant numbers of fatal bleeds reported to the FDA. The lack of a reversal agent is believed to be the cause of the significant number of bleeding-related adverse events.
Within the first 14 months of its approval, Pradaxa was linked to more than 900 gastrointestinal bleeds and 500 bleeding deaths. Boehringer, in an official statement on November 2, 2011, linked about 50 bleeding deaths to Pradaxa, which Boehringer asserted is consistent with expectations from the Pradaxa clinical trials.
Earlier this year, the FDA required Boehringer to modify the Pradaxa warning label to reflect the lack of a reversal agent, which had not been included in the original warnings. The FDA is currently evaluating the reports of bleeding deaths and investigating whether the rate of severe bleeding reports is higher than what was seen in Pradaxa clinical trials. At this point, there is no black box warning for Pradaxa.
However, in February 2013, the FDA approved new language on Pradaxa’s safety label to include new warnings, precautions and contraindications informing patients not to take the drug if they have ever had or plan to have a valve in their hearts replaced. The updated safety label and medication guide comes after an interim analysis of results from a study showed increased incidents of thromboembolic events (blood clots) and bleeding events in patients with mechanical prosthetic heart valve replacements who used the new anticoagulant.
TESTIM is a prescription medicine used to treat adult males who have low or no testosterone. It is a testosterone-containing gel that is applied to the skin of the shoulders and upper arms. Secondary exposure to testosterone in children and women can occur with the use of testosterone gel in men. Reported cases involved children ranging in age from 9 months to 7 years old.
Physicians should advise patients of the reported signs and symptoms of secondary exposure, which may include the following:
- In children: unexpected sexual development including inappropriate enlargement of the penis or clitoris, premature development of pubic hair, increased erections, aggressive behavior and advanced bone age.
- In women: changes in hair distribution, increase in acne, or other signs of testosterone effects.
TESTIM is manufactured for Auxilium Pharmaceuticals, Inc., by DPT Laboratories, Ltd. It was approved by the FDA in October 2002. There were approximately 400,000 prescriptions dispensed for Testim 1% in 2008.
Since the initial marketing approval of testosterone gel in 2000 to May 2009, FDA’s Adverse Event Reporting System (AERS) has received 20 pediatric postmarket reports of secondary exposure to topical testosterone gel.
The FDA placed a boxed warning about the risks of TESTIM 1% to children and women in September 2009, as well as updated safety labeling changes to the Warnings, Precautions and Adverse Reactions sections of the label.
The area where the gel is applied should be covered, and patients are warned that others should not come into contact with the skin where the gel was applied.
The possibility of secondary exposure to testosterone gel should be brought to the attention of a health care provider.
In at least one reported case of secondary exposure to testosterone in children, the reporter considered the possibility of secondary exposure from items such as the testosterone gel user’s shirt and other fabrics such as towels and sheets.
In most cases, signs and symptoms of testosterone exposure regressed with the removal of the testosterone gel exposure. However, there were cases where enlarged genitalia did not fully return to age appropriate normal size, and bone age remained modestly greater than chronological age.