- Prescribing Advice for GPs - https://www.prescriber.org.uk -

New Contra-indications and Warnings for Pioglitazone

The European Medicines Agency (EMA) has recommended (PDF) several new contra-indications and warnings for pioglitazone (Actos®) to minimise the impact of a small increased risk of bladder cancer.

The review concluded that "these medicines remain a valid treatment option for certain patients with type 2 diabetes" but that "the small increased risk could be reduced by appropriate patient selection and exclusion".

Clinicians are advised to not use pioglitazone in:

Risk factors for bladder cancer should be assessed before starting treatment, especially in older patients and treatment should be regularly reviewed and only continued when treatment continues to provide a benefit.

The relative risk of bladder cancer from three recent observational studies ranges from 1.12 to 1.33. A meta-analysis of randomised controlled trials indicated an absolute risk increase of 0.08% (7 cases in 10,212 patients or 0.07% risk in the placebo group versus 19 cases in 12,506 patients or 0.15% in the treatment group).

The EMA has also requested that a pan-European epidemiological study is conducted to provide more robust information about the risk.

Action: Clinicians should be aware of this review and the additional warnings and contra-indications for pioglitazone. The figures quoted in the review may be helpful when explaining the risks to patients.

UPDATE: A summary is now available from the Medicines and Healthcare products Regulatory Agency (MHRA).