What is the interaction between Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Clopidogrel (Plavix)?

From the Guidelines

Taking NSAIDs with Plavix (clopidogrel) should be avoided due to increased bleeding risk, and if necessary, the lowest effective dose of NSAID should be used for the shortest duration while monitoring for signs of bleeding, as recommended by the 2010 expert consensus document 1. When considering the use of NSAIDs with Plavix, it's crucial to weigh the benefits against the potential risks, particularly the risk of gastrointestinal bleeding.

• The combination of NSAIDs and Plavix can lead to a "double hit" on the blood clotting system, significantly increasing the risk of bleeding, especially gastrointestinal bleeding 1.
• Patients with prior gastrointestinal bleeding are at the highest risk for recurrent bleeding on antiplatelet therapy, and the use of NSAIDs further increases this risk 1.
• The use of proton pump inhibitors (PPIs) can reduce the risk of upper gastrointestinal bleeding in patients taking NSAIDs or aspirin, but the concomitant use of PPIs and thienopyridines like clopidogrel may have inconsistent effects on cardiovascular outcomes 1.
• If pain management is necessary for patients on Plavix, acetaminophen (Tylenol) is a preferred alternative to NSAIDs, as it does not affect platelet function in the same way 1.
• Patients taking NSAIDs with Plavix should be monitored closely for signs of bleeding, including black/tarry stools, coffee-ground vomit, unusual bruising, or prolonged bleeding from cuts, and should consult their healthcare provider before combining these medications or making any changes to their prescribed regimen.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

NSAIDs and Plavix Interaction

• The use of nonsteroidal anti-inflammatory drugs (NSAIDs) with antithrombotic therapy, such as Plavix (clopidogrel), is associated with an increased risk of bleeding, mainly gastrointestinal 2.
• A study found that the risk of hospitalization for gastrointestinal bleeding after exposure to NSAIDs was increased in patients receiving antiplatelet therapy, with an adjusted odds ratio of 1.44 (95%CI, 1.07-1.94) 2.
• Another study found that the use of a COX-2 inhibitor plus a proton-pump inhibitor (PPI) did not have a significant advantage over traditional NSAID plus a PPI in reducing the risk of gastrointestinal events in high-risk patients 3.
• The use of PPIs was found to not increase the risk of lower gastrointestinal bleeding (LGIB) in patients taking NSAIDs, aspirin, clopidogrel, or warfarin 4.
• A study comparing hospitalization rates for gastrointestinal events between users of traditional NSAIDs plus PPIs and users of COX-2 inhibitors found that COX-2 inhibitors had a lower risk of gastrointestinal events 5.
• NSAIDs are associated with an increased risk of both upper and lower gastrointestinal complications, and co-therapy with PPIs reduces the risk of upper but not lower gastrointestinal complications 6.

Gastrointestinal and Cardiovascular Risks

• The risk of gastrointestinal and cardiovascular adverse events associated with NSAIDs should be considered when prescribing these medications, especially in elderly patients 6.
• COX-2 selective agents are safer for the gastrointestinal tract but have a worse cardiovascular profile, while naproxen seems safer for the cardiovascular system but has higher gastrointestinal toxicity 6.
• The prescription of type and dose of NSAIDs should be individualized based on the stratification of the cardiovascular and gastrointestinal risk of patients 6.