EMA Reviewing Safety of NSAIDs, Clarifies on Pioglitazone

October 21, 2011

October 21, 2011 (London, United Kingdom) — The European Medicines Agency (EMA) has launched a new review of the cardiovascular safety of nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) [1], while also clarifying a previous opinion on the use of the antidiabetic agent pioglitazone (Actos, Takeda) and the risk of bladder of cancer [2].

In 2011, the EMA recommended that new contraindications and warnings be added to the label of pioglitazone, noting there was a small increased risk of bladder cancer with the diabetes drug. Today, the agency confirmed their previous opinion, with the earlier warnings and contraindications remaining in place, but provided some clarification on its use. The EMA stated that pioglitazone should be used as a second- or third-line treatment, noting it "remains a valid treatment option for certain patients with type 2 diabetes, when certain other treatments (metformin) have not been suitable or have failed to work adequately."

Based on the earlier recommendations, the EMA continues to recommend against the use of pioglitazone in patients with current or a history of bladder cancer, or those with uninvestigated macroscopic hematuria. Before use in any patient, physicians should take into account risk factors for bladder cancer, especially in older patients, according to the EMA.

In June 2011, the US Food and Drug Administration informed physicians that using pioglitazone for more than 12 months was associated with an increased risk of bladder cancer, and revised the drug's label to highlight the risks. French regulators suspended sales of pioglitazone, also in June 2011, while German health authorities said it should not be started in new patients.

NSAIDs Also Under Review

In a separate statement, the EMA also said that it has begun a new review of the latest data on the cardiovascular safety of nonselective NSAIDs. In 2006, the EMA's Committee for Medicinal Products for Human Use (CHMP) concluded the drugs were safe for use, with a positive overall risk–benefit profile, but was unable to rule out a small risk of thrombotic events, especially when used at high doses or for long durations.

Since 2006, new studies on the cardiovascular safety of NSAIDs have been published, including data from the Safety of Nonsteroidal Anti-inflammatory Drugs (SOS) project, led by investigators from Erasmus University in Rotterdam, Germany, the EMA notes. CHMP is currently reviewing data from SOS, as well from other clinical trials, epidemiological studies, and postmarketing reports, to determine if there is a need to update their 2006 opinion on the safety of NSAIDs.


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