Use pioglitazone only in selected patients, says EMA guidance

Pioglitazone remains a valid treatment option for certain, selected patients with type 2 diabetes but should be avoided in those with a history of bladder cancer, or with uninvestigated haematuria, warns the latest guidance from the European Medicines Agency. It adds that doctors must monitor regularly all patients who take pioglitazone-containing medicines (Actos, Glustin, Competact, Glubrava and Tandemact).

The EMA’s Committee on Medicinal Products for Human Use (CHMP) reported that it had finalised its benefit-risk review of pioglitazone, which it undertook after concerns were raised about an association between use of the drug and an increased risk of bladder cancer.

The CHMP examined all available data on bladder cancer, from preclinical and clinical studies, epidemiological studies and spontaneous reports, as well as consulting with its Scientific Advisory Group (SAG) on Diabetes/Endocrinology.

It found that there is a small increased risk of bladder cancer in people taking pioglitazone, especially for longer periods and at higher cumulative doses – but the CHMP added that “the small increased risk could be reduced by appropriate patient selection and exclusion”.

It concluded that the benefits of pioglitazone outweigh the risks in patients who respond to treatment and that the drug remains a valid treatment option for some people.

The Committee warned that pioglitazone should not be initiated or continued by people with a history of bladder cancer or who have uninvestigated macroscopic haematuria. And it said that prescribers should review the treatment of patients on pioglitazone after 3-6 months (and at regular intervals thereafter) to ensure that only those patients who are deriving sufficient benefit continue to take it. It warned that the benefit-risk balance should be assessed particularly carefully in the elderly, because of age-related risks.

In the US, the Food and Drug Administration made a formal safety announcement in June warning patients that taking pioglitazone for more than one year may be associated with an increased risk of bladder cancer, and said that this information should be added to the Warnings and Precautions section of the label for all pioglitazone-containing medicines.