FDA Alert: The FDA continues to assert that NSAIDs can increase the risk of heart attacks and strokes.

Kristen Reynolds, PhD and Cody Greenlaw, PharmD
PGXL Laboratories

What’s the issue?

On July 9, 2015, the U.S. Food and Drug Administration (FDA) issued a safety advisory regarding increased risk of cardiovascular events in patients taking non-steroidal anti-inflammatory drugs (NSAIDs). The advisory indicates that non-aspirin NSAIDs, commonly taken for pain and fever, can increase the risk of heart attack and stroke even in patients without other known heart disease risk factors. The increased risk can occur within the first weeks of NSAID use, and may increase with longer duration of therapy and higher dosages.

What are the risks and medications involved?


NSAIDs include many common prescription and over-the-counter (OTC) medications such as celecoxib (Celebrex), ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn), meloxicam (Mobic), and diclofenac (Cataflam, Voltaren), among others. Two former NSAIDs, rofecoxib (Vioxx) and valdecoxib (Bextra), were withdrawn from the U.S. market due to increased risk of cardiovascular-related events.

NSAIDs can increase the risk of heart attack and stroke in virtually everyone – not only vulnerable individuals, but healthy individuals too. Still, it should be noted that patients with heart disease or who have heart disease-related risk factors such as hypertension, diabetes, or smoking are at an even greater risk than those who do not have these additional risk factors. The anti-inflammatory properties of NSAIDs increase risk through the creation of a pro-thrombotic state that can lead to high blood pressure, buildup of artery plaque, and clot formation.

How can PGXL PRIMER™ help?

Most NSAIDs are metabolized by the liver through cytochrome P450 enzymes, notably, CYP2C9. Approximately 40% of the general population has an inherited variation in CYP2C9 which decreases clearance of NSAIDs. These Intermediate and Poor Metabolizers of CYP2C9 are at risk of higher-than-normal drug exposure even at standard dosages since they metabolize and excrete the drug at a much slower rate. Higher drug exposure may further increase the cardiovascular risks.

In addition to genetic differences, other medications may interfere with CYP2C9’s ability to clear NSAIDs from the body. This type of drug-drug interaction may further increase risk of cardiovascular events. Examples of these interfering drugs include amiodarone, fluconazole, fluvoxamine, and voriconazole.

The PGXL PRIMER™ system can identify if a patient has a CYP2C9 gene conflict that affects NSAID risk and can also reconcile any risks for drug-drug interactions. PGXL pharmacists will use those interactions identified through PRIMER to reconcile all known risk factors for NSAID use, and provide considerations for dose adjustments or alternative medications.

What can you do?

All in all, NSAIDs have the potential to increase the risk of cardiovascular events. This potential doesn’t apply to just “vulnerable” individuals – healthy people can be affected, too. All prescription and OTC medications that contain a NSAID will have these new risks highlighted in the drug labeling. To minimize the risk for developing a cardiovascular event when using NSAIDs, the lowest effective dose should be used for the shortest duration possible. Patients should be informed about the signs and symptoms of serious events and the steps they should take if symptoms occur.

PGXL PRIMER™ can identify additional risk factors through genotyping and medication reconciliation in order to provide safer alternative considerations in patients with high risk.

The full FDA advisory and list of NSAIDs can be found HERE. Information about ordering PRIMER™ can be found HERE.

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