NEW YORK (Reuters Health) - A review of official reports of bad drug reactions is revealing more signs that people taking the diabetes drug Actos are at higher risk of developing bladder cancer.
Between 2004 and 2009, more than half a million adverse reactions among people taking anti-diabetic drugs were added to an official U.S. Food and Drug Administration database. Among those reports were 138 instances of bladder cancer in patients taking at least one of more than 15 different anti-diabetic drugs.
However, more than a fifth of those bladder cancers were in patients taking Actos (pioglitazone), suggesting a “disproportionate risk” in comparison with other anti-diabetics, said study author Dr. Elisabetta Poluzzi of the University of Bologna in Italy.
A certain number of people taking a drug will always develop other problems, she explained, and it’s often not clear whether those problems stem from the drug itself. As a result, these findings do not show Actos increases the risk of bladder cancer, she cautioned - just that researchers should look into it further.
“Disproportion is indicative of possible risk,” Poluzzi told Reuters Health in an email, “not of an actual risk.”
Still, this is not the first report to tie the drug to bladder cancer, and the possibility of increased cancer risk is already included in the prescribing information for the drug.
Last year, the FDA began a safety review of Actos after receiving early results from a long-term study by the drug’s maker, Takeda Pharmaceutical Co Ltd. That study showed a raised risk of bladder cancer in patients with the longest exposure to Actos, and in those with the highest cumulative dose of the drug.
Actos is in the same class of drugs as GlaxoSmithKline’s Avandia, which has not been associated with bladder cancer but has been linked to heart risks.
The FDA has said patients should not stop taking Actos unless told to do so by their doctor.
To investigate the question further, Poluzzi and her colleagues reviewed reports of negative reactions submitted to the FDA’s official Adverse Event Reporting System, launched in 1969.
It’s an imperfect system, she and her colleagues note in the journal Diabetes Care - for one, manufacturers are required to report to the FDA any health problem they suspect stems from one of their products, but for doctors, patients, lawyers, and anyone else who reports these reactions, it’s entirely voluntary. As a result, the number of FDA reports does not equal the true number of bad reactions to drugs.
The data are also influenced by what is known as “notoriety bias,” Poluzzi added, in which the number of reports of bad reactions typically rises after warnings - such as a new study - suggest that they could occur.
However, the scientists also saw disproportionate cases of bladder cancer among Actos users in the years before a major 2005 study suggested that a link might exist.
It’s not clear how Actos might increase the risk of bladder cancer, Poluzzi added. The drug treats diabetes by activating certain receptors on cells - much as a key opens or closes a lock, and this same mechanism may also encourage some cells to become cancerous, she said.
Bladder cancer is the sixth most common cancer in the U.S. According to the National Cancer Institute, there were about 70,000 new cases diagnosed nationwide in 2010, and close to 15,000 deaths from the disease.
“Until the final data of the FDA investigation are available, physicians should pay careful attention to this possible risk,” Poluzzi and her colleagues write.
SOURCE: bit.ly/fRMKux Diabetes Care, online April 22, 2011.