Taking the diabetes drug Actos may increase one’s risk of developing bladder cancer, Health Canada and the drug’s maker, Takeda Canada Inc., say.
The statement was the culmination of a safety assessment Health Canada announced last June, two days after the U.S. Food and Drug administration issued a warning similar to the one the Canadian drug regulator just announced.
Health Canada said the drug’s labelling will be changed to reflect the potential risk.
Actos is the brand name for pioglitazone, a drug from the glitazone family used for the treatment of Type 2 diabetes. It is a sister drug to Avandia, a once widely used diabetes drug that fell out of favour after studies found it increased users’ risk of heart disease.
While it was thought that Actos was safer than Avandia – at least in terms of heart disease – there have been suggestions for awhile that using the drug, especially long-term, might increase one’s risk of developing bladder cancer.
Takeda is conducting a 10-year study trying to see if the link is real. Data from the midway point of the study points to the possibility that it is, Health Canada said in its statement.
What risk factors are
More than 10,000 people are diagnosed with bladder cancer each year in the UK. Not counting non melanoma skin cancer, bladder cancer is the 7th commonest cancer in the UK. It is the 4th commonest cancer for men and the 11th most common for women.
More men than women get bladder cancer. This may just be because more men than women have smoked in the past few decades. And more men have been exposed to chemicals at work.
Your ethnic background is also related to your risk. Black men have about half the risk of bladder cancer of white men. Black women have about two thirds the risk of white women. Risk in Asian men and women is even lower.
Bladder cancer usually takes a long time to develop and it is most common in older people. Most people with bladder cancer are between 50 and 80 years old. It is rare in people under 40.
Dr. Muhammad Mamdani, director of the Applied Health Research Centre of the Li Ka Shing Knowledge Institute at Toronto’s St. Michael’s Hospital, said the warning likely won’t impact that many people, because doctors have been moving their patients off the drug over the past few years.
Diabetes treatment options
In fact, in Ontario Actos is no longer on the list of drugs that doctors can freely prescribe; it has been moved to the “exceptional access” list and can only be prescribed with approval, Mamdani said.
People who have type 2 diabetes have a 40% increase in their risk of developing bladder cancer.
Repeated bladder infections
Some studies in the past have seemed to show that if you have had many bladder infections, or suffer from chronic bladder infection, you may be more at risk of bladder cancer. The risk is particularly high for a type called squamous cell cancer of the bladder. But one recent study did not find an increase in risk for people with a history of common bladder infections and one study actually showed a decrease in risk in women. So we need more research to find out if there is a link between bladder infections and bladder cancer.
Smokers who have repeated bladder infections may have a much higher risk, with one study reporting a risk 10 times higher than the general population. Recent studies have found that men who have had gonorrhoea infection also have an increased risk of bladder cancer.
In the developing world, parasitic infection is the main cause of bladder cancer. A parasite called bilharzia or schistosomiasis is widespread in many countries and increases the risk of squamous cell bladder cancer. But in the UK, parasitic infection is extremely rare and infection is a much less common cause of bladder cancer than smoking or workplace chemicals.
Bladder stones are little lumps of calcium that can form in the urinary system. You can get kidney or bladder stones. If you have stones in the bladder (sometimes called bladder calculi), you may be more at risk from a type of bladder cancer called squamous cell bladder cancer. This is because stones can cause chronic infection. But you would need to suffer from this for a long time before it would increase your risk of bladder cancer.
Dr. David Juurlink, head of the division of clinical pharmacology at the University of Toronto, said at this point there is little need to resort to this drug, unless a patient has done extraordinarily well on it in the past.
“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,” said Juurlink, who actively campaigned to get Avandia out of use.
“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?”
Juurlink suggested that anyone taking the drug who has concerns about this news should speak to their doctor.
The Health Canada statement noted that in the Takeda trial, people who weren’t using the drug developed bladder cancer at a rate of about seven cases in every 10,000 people. But there were 10 cases per 10,000 people among the people using Actos for control of Type 2 diabetes.
The statement says the risk appears to be highest for people who took the drug for the longest duration or at the highest dosages, but it isn’t possible to rule out a risk even after short-term use.
The drug regulator suggests that Actos should not be used to treat patients with active bladder cancer, a history of bladder cancer or uninvestigated blood in their urine.
It also suggested doctors should assess a patient’s risk for bladder cancer before starting treatment with this drug. Known risk factors include age, smoking, a family history of bladder cancer, exposure to chemicals in the workplace, certain cancer treatments and radiation therapy.
The Canadian Press