Health Canada just announced that Type 2 diabetes drug, Actos, raises risks for bladder cancer. Actos maker, Takeda Canada, Inc., was part of the joint announcement.
The statement followed a safety assessment announced last June by Health Canada, two days following release of a similar warning by the U.S. Food & Drug Administration (FDA) said CBC News. Actos (pioglitazone) labeling will be changed to reflect the possible risk, said Health Canada.
Last June, the U.S. Food & Drug Administration (FDA) issued a safety communication stating that use of Actos for more than one year may be associated with an increased risk of bladder cancer. The June safety communication followed a prior September 2010 communication indicating that preliminary data from Kaiser Permanente research demonstrated that bladder cancer risks rises with increasing Actos dose and duration, reaching statistical significance after 24 months. Bladder cancer concerns caused regulators in France and Germany to suspend sales of Actos in those countries over the summer. Takeda officially recalled Actos from the French market in July.
Takeda is conducting a 10-year study to determine the risk; however, data received from the study’s midpoint indicates that the risk may be real, said Health Canada. In Ontario, Actos is no longer readily available to physicians and is now on its “exceptional access list,” which means Actos can only be prescribed with approval, Dr. Muhammad Mamdani, director of the Applied Health Research Centre of the Li Ka Shing Knowledge Institute at Toronto’s St. Michael’s Hospital, told CBC News. Dr. Mamdani noted that doctors have been moving patients off Actos in recent years.
Dr. David Juurlink, head of the division of clinical pharmacology at the University of Toronto, told CBC News, “I personally would not be comfortable using it as a long-term therapy because bladder cancer is … not something that’s reversible. It’s not a skin rash that goes away when you stop the drug.” Dr. Juurlink added, “ We’ve got other options. And when you’ve got other options why would you take an option that has some well-established side-effects and some side-effects that are less well established but ones that you would for sure rather avoid?”
The Health Canada statement noted that in the Takeda trial, those not taking Actos developed bladder cancer at a rate of roughly seven cases in every 10,000 people, which increased to 10 cases in Actos patients, said CBC News. The risk is greatest for patients on Actos the longest and taking the highest dosage.
Health Canada suggests Actos be avoided in patients with active bladder cancer, a history of bladder cancer, or uninvestigated blood in their urine. Physicians should also assess patients’ risks for bladder cancer before prescribing Actos—age, smoking, a family history of bladder cancer, exposure to chemicals in the workplace, certain cancer treatments, and radiation therapy, said CBC News.
Meanwhile, we recently wrote that a former medical reviewer for Takeda accused the company of downplaying Actos bladder cancer cases, as well as congestive heart failure, when reporting adverse events to the FDA. Allegations were made in an Actos whistleblower lawsuit—first filed by Helen Ge in 2011—that was recently unsealed in U.S. District Court, District of Massachusetts.
Ge claimed her contract with Takeda was ended when she complained about how Takeda instructed medical reviewers to report Actos adverse events to the FDA. Ge alleged that she personally reviewed at least 10 bladder cancer cases reported by Yale University involving Actos patients enrolled in a post-market study investigating Actos and bladder cancer. Ge further claimed that Yale reported at least 40 other subjects in that study were diagnosed with bladder cancer while taking Actos. Though Yale reported all of the cases as “related to” Actos, Ge claimed that when she attempted to report them to the FDA database, she was directed to change her assessment by her superiors and Takeda-Japan. Ge also alleged that Takeda’s adverse event database for Actos held more than 100 bladder cancers reported to the company, but only 72 were reported to the FDA, which Dr. Ge referred to as “a serious discrepancy.”