New Information for Healthcare Professionals
Concomitant Use of Ibuprofen and Aspirin
New Information
[9/2006] - Concomitant Use of Ibuprofen and Aspirin:
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.
Healthcare professionals should advise consumers and patients
regarding the appropriate concomitant use of ibuprofen and
aspirin.
This information reflects FDA’s current analysis of data available to FDA concerning these drugs. FDA intends to update this sheet when additional information or analyses become available.
To report serious adverse events associated with the use of these drugs, please contact the FDA MedWatch program using the contact information at the bottom of this sheet.
Considerations
Health care professionals should consider:
- Counseling patients about the appropriate timing of ibuprofen
dosing if they are also taking aspirin for cardioprotective
effects.
- With occasional use of ibuprofen, there is likely to be
minimal risk from any attenuation of the antiplatelet effect of
low dose aspirin, because of the long-lasting effect of aspirin on
platelets.
- Patients who use immediate release aspirin (not enteric
coated) and take a single dose of ibuprofen 400 mg should dose the
ibuprofen at least 30 minutes or longer after aspirin ingestion,
or more than 8 hours before aspirin ingestion to avoid attenuation
of aspirin’s effect.
- Recommendations about the timing of concomitant use of
ibuprofen and enteric-coated low dose aspirin cannot be made based
upon available data.
- Other nonselective OTC NSAIDs should be viewed as having
the potential to interfere with the antiplatelet effect of low-dose
aspirin unless proven otherwise.
- Prescribing analgesics that do not interfere with the
antiplatelet effect of low dose aspirin for high risk populations.
Data Summary
Aspirin is available over-the-counter as a tablet, buffered
tablet, effervescent tablet, or caplet in immediate-release
formulations and as a tablet in enteric-coated formulations.
Individual aspirin doses range from 81 mg to 500 mg.
It has been demonstrated in published and unpublished human ex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.6 FDA is unaware of studies that have
looked at the same type of interference by ketoprofen with low dose
aspirin, and there are no data looking at nonprescription doses of
naproxen. There is at least one study that has suggested that
naproxen at higher than nonprescription doses may interfere with
aspirin’s anti-platelet activity when they are co-administered.
Acetaminophen appears to not interfere with the antiplatelet effect
of low dose aspirin, and FDA is unaware of any interference by
narcotic analgesics.
Implications
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.
Report serious adverse events to
FDA’s MedWatch reporting system by completing a form on line at
http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178),
by mail using the postage-paid address form provided online
(5600 Fishers Lane, Rockville, MD 20852-9787),
or by telephone (1-800-FDA-1088).
Questions? Call Drug Information, 1-888-INFO-FDA
(automated) or 301-827-4570
Druginfo@fda.hhs.gov
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Date created: September 8, 2006 |