Use of Medications Containing Pioglitazone (Actos®) Suspended in France and Germany

On June 9, 2011, the French Agency for the Safety of Health Products (Afssaps) decided to suspend use in France of medications containing pioglitazone effective July 11, 2011, based on an opinion from the French Marketing Authorisation Committee (MA) and the French National Pharmacovigilance Committee. The results from a study conducted by the CNAMTS at the request of Afssaps, which have just been made public, confirm that there is a slight increase in the risk of bladder cancer in patients treated with pioglitazone.

To date, some 230,000 patients in France have been treated with pioglitazone. Analysis of preclinical, clinical, epidemiological and drug safety data indicated a potential risk of bladder cancer in diabetic patients treated with pioglitazone and led the French National Pharmacovigilance Committee to issue an opinion and solicit the MA commission for further investigation. On April 7th, the MA asked to see the results from a broad-scale cohort study conducted by the CNAMTS at Afssaps request before issuing an opinion. In the meantime, on April 19th, the Afssaps issued an advisory to healthcare professionals concerned with the use of pioglitazone in long-term treatment of diabetes patients. The available drug safety data, along with the new results from the study presented to the members of the MA commission to date by the National Health Insurance System (CNAMTS), confirm that the use of pioglitazone carries a slight risk of bladder cancer. The MA commission ruled that the risk/benefit ratio for this product was now unfavourable.

Summary of the Study Conducted by the National Health Insurance Agency

Risk of bladder cancer in diabetics treated with pioglitazone in France:
A Cohort Study Using Data from the SNIRAM and PMSI

This is the broadest study ever done on this subject. Its main objective was to identify, in diabetics treated in France, the existence of any eventual correlation between exposure to pioglitazone and the risk of occurrence of bladder cancer.

This study was done on a cohort of 1,491,060 diabetics on special drug therapy, ages 40- 79. It covered the period from 2006-2009. The group exposed to pioglitazone included 155,535 people with diabetes and the group not exposed contained 1,335,525 persons.

Analysis of this cohort of diabetes patients monitored in France between 2006 and 2009 supports the hypothesis that there is a statistically significant correlation between exposure to pioglitazone and the occurrence of bladder cancer. The results found are similar to those obtained in the United States for the cohort in the Kaiser Permanente Northern California study.

The Afssaps requested that patients who were being treated with a medication containing pioglitazone (Actos® and Competact®) not suspend their treatment due to the dangers of stopping treatment, but that they should consult with their physician immediately on adapting their diabetes treatment. Physicians must no longer prescribe medications containing pioglitazone.

On June 10, 2011, Germany’s Federal Institute for Drugs and Medical Devices (BfArM) said it had decided to follow suit after receiving the CNAMTS results. “BfArM recommends the suspension of approval of pioglitazone (Actos) until further clarification. Doctors should not put new patients on pioglitazone,” the German regulator said in a statement.

Other European countries are not yet recommended any changes to Actos use but are awaiting a European Medicines Agency review. The European Medicines Agency is currently reviewing results from pharmacoepidemiological studies, non-clinical and clinical data and post-marketing reports on pioglitazone-containing medicines and the occurrence of bladder cancer, to assess their impact on the balance of benefits and risks of these medicines. The Committee for Medicinal Products for Human Use (CHMP) will finalise its review in July and make recommendations on the future use of these medicines.

Related Reading:
AFSSAPS: Press Release – Use of Medications containing Pioglitazone Suspended (french)

REUTERS: Germany joins France in suspending top Takeda drug

EUROPEAN MEDICINES AGENCY: Updates on ongoing benefit-risk review of pioglitazone-containing medicines