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FDA investigates possible safety concerns over clopidogrel

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4th February 2009

The US Food and Drug Administration has published information about an ongoing safety review of clopidogrel. This follows reports suggesting it is less effective in some patients than it is in others, including those taking proton pump inhibitors. However, details of the particular patient groups likely to be affected are not known yet and it is therefore important to consider these preliminary safety reports with caution while this is investigated.

Action
The Food and Drug Administration (FDA) points out that it has not concluded that there is a cause and effect relationship between clopidogrel and the emerging safety issue. Until further information is available the FDA recommends the following:

  • Healthcare providers should continue to prescribe and patients should continue to take clopidogrel as directed, because clopidogrel has demonstrated benefits in preventing blood clots that could lead to a heart attack or stroke.
  • Healthcare providers should re-evaluate the need for starting or continuing treatment with a proton pump inhibitor (PPI), including over-the-counter (OTC) use, in patients taking clopidogrel.
  • Patients taking clopidogrel should consult with their healthcare provider if they are currently taking or considering taking a PPI.

Healthcare professionals should continue to follow NICE guidance on prescribing clopidogrel (see below) but be aware of this possible safety concern, and report suspected adverse drug reactions with clopidogrel to the Medicines and Healthcare products Regulatory Agency (MHRA) through the Yellow Card Scheme.

What is the background to this?
Published reports have suggested that clopidogrel is less effective in some patients than it is in others. Differences in effectiveness may be due to genetic differences in the way the body metabolises clopidogrel or because using certain other drugs with clopidogrel can interfere with how the body metabolises it. Some reports suggest that certain PPIs may make clopidogrel less effective. However, others do not suggest this interaction occurs.

The manufacturers, Sanofi-Aventis and Bristol-Myers Squibb, have agreed to work with the FDA to conduct studies to obtain additional information that will allow them to better understand and characterise the effects of genetic factors and other drugs (especially the PPIs) on the effectiveness of clopidogrel. It is likely to take several months to complete the studies and analyse the results. The FDA will subsequently publish its conclusions and any recommendations.

As well as considering the recommendations made by the FDA, healthcare professionals should continue to follow NICE guidance on prescribing clopidogrel. NICE guidance on the use of clopidogrel in acute coronary syndrome (ACS) recommends the use of clopidogrel in combination with low-dose aspirin in patients who have non-ST elevation ACS who are at moderate to high risk of myocardial infarction or death. The guidance defines this higher risk as patients with ECG changes and/or raised cardiac markers. NICE guidance on secondary prevention of occlusive vascular events, which applies to patients who have had an occlusive vascular event or have symptomatic peripheral arterial disease, recommends clopidogrel on its own for those who are intolerant of low-dose aspirin. Aspirin intolerance is defined as proven hypersensitivity to aspirin-containing medicines or a history of severe dyspepsia induced by low-dose aspirin.

Further information on the use of clopidogrel is available on the acute coronary syndrome and other cardiovascular sections of NPC.

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