Ibuprofen can interfere with the anti-platelet effect of low dose Aspirin ( 81 mg per day ), potentially rendering Aspirin less effective when used for cardioprotection and stroke prevention.

It has been demonstrated in published and unpublished human ex vivo studies, that Ibuprofen interferes with the antiplatelet activity of low dose Aspirin ( 81 mg, immediate release ) when they are ingested concurrently.

The mechanism by which this occurs may be through competitive inhibition of the acetylation site of cyclooxygenase ( COX ) in the platelet.
Both Ibuprofen ( reversible inhibition ) and Aspirin ( irreversible inhibition ) occupy nearby sites on COX, such that the presence of Ibuprofen interferes with Aspirin binding.
Once the Ibuprofen releases from the binding site, COX will not be inhibited because some Aspirin available to bind will have been excreted.
This Ibuprofen interference attenuates the expected Aspirin-mediated irreversible inhibition of thromboxane B2 ( TXB2 ) production and the expected inhibition of platelet aggregation.

There are no clinical endpoint studies conducted specifically to evaluate the interaction.
Attenuation of 90% or more of the antiplatelet effect of Aspirin has been defined as clinically significant by some investigators.

Unpublished single dose trials with Ibuprofen 400 mg indicate that interference with Aspirin’s antiplatelet activity, as measured by TXB2 levels and platelet activation studies, occurs when Ibuprofen is taken within 30 minutes after immediate release aspirin dosing.
The interaction also occurs when a single dose of Ibuprofen 400 mg is taken 8 hours or less prior to Aspirin dosing.
At least 8 hours should elapse after Ibuprofen dosing, before giving Aspirin, to avoid significant interference.

One study showed that the antiplatelet effect of enteric-coated low dose Aspirin is attenuated when Ibuprofen 400 mg is dosed 2, 7, and 12 hours after Aspirin.

The clinical implication of the interference by Ibuprofen on the anti-platelet effect of Aspirin is unclear. However, it is potentially important because the cardioprotective effect of Aspirin, when used for secondary prevention of myocardial infarction, could be decreased or negated.

Source: FDA, 2006


XagenaMedicine2006