EMA reassesses cardiovascular safety of rosiglitazone-containing medicines (Avandia, Avandamet and Avaglim)

In July, the Committee for Medicinal Products for Human Use (CHMP) under the European Medicines Agency (EMA) once again initiated a review of the benefit-risk profile of rosiglitazone-containing medicines, which in Denmark are used to a very limited degree for the treatment of type 2 diabetes. We remind doctors to pay strict attention to the restrictions appearing from the summaries of product characteristics for any medicine. The CHMP is expected to finalise its scientific review by September 2010.

Avandia was initially authorised in the European Union in July 2000 as treatment for type 2 diabetes when other treatments have either failed or are unsuitable for a specific patient. Avandia has been contraindicated in patients with heart failure or a history of heart failure since its first authorisation. Rosiglitazone was subsequently approved in combination with metformin (Avandamet) and with glimepiride (Avaglim). Since then, the use of these medicines has been further restricted several times by new warnings and contraindications on their use in patients with heart problems.

The CHMP initiated a scientific review of rosiglitazone on 9 July 2010 following the publication of two recent studies (1, 2) on the cardiovascular safety of rosiglitazone. The CHMP will review these studies together with all other available scientific data on rosiglitazone's positive and negative effects.
Until the CHMP finalises its review, the Danish Medicines Agency urges doctors to observe the indications, contraindications and warnings listed in the current summaries of product characteristics, paying special attention to the following:

• Rosiglitazone is contraindicated in patients with current or previous heart failure (NYHA class I-IV) and in patients with acute coronary syndrome (unstable angina, non-ST segment elevation myocardial infarction (NSTEMI) and ST segment elevation myocardial infarction (STEMI);
• Rosiglitazone and insulin should only be used together in exceptional cases and under close supervision;
• The use of rosiglitazone is not recommended in patients with ischaemic heart disease or peripheral arterial disease.

Patients who wish to have more information about rosiglitazone-treatment should contact their doctor. Patients are advised not to stop rosiglitazone treatment without consulting their doctor.

The Danish summaries of product characteristics are available in the factbox to the right. You can find the English versions at the EMA website, www.ema.europa.eu. EMA's press release is available to the right.


For further information, please contact Chief Medical Officer Jens Heisterberg, tel. +45 4488 9198.

Danish Medicines Agency, 23 July 2010

Notes:

1. Graham DJ et al. Risk of acute myocardial infarction, stroke, heart failure, and death in elderly Medicare patients treated with rosiglitazone or pioglitazone. JAMA doi:10.1001/jama.2010.920.
2. Nissen SE et al. Rosiglitazone revisited. An updated meta analysis of risk for myocardial infarction and cardiovascular mortality. Arch Intern Med doi:10.1001/archinternmed.2010.207.