February 5th, 2009
PPIs and Plavix: There Are No Simple Answers but Maybe a Simple Solution!
In response to my earlier post on PPIs and upper GI bleeding, Bahman N Shokouhi writes:
A recent article in the Canadian Medical Association Journal (published online Jan 28, 2009), suggests that this is not a class effect and that Pantoprazole does not seem to have an effect. It has been suggested that the cause of this is the effect of most PPIs on P450 2C19. Pantoprazole does not affect P450 2C19 and therefore according to the data does not reduce the effectiveness of clopidogrel. So, hopefully if we start using Pantoprazole instead of Omeprazole and other PPIs you can still continue with your calls!
However, we should remember that we do not know if any PPI clearly has a detrimental effect on Plavix’s action. Until we know whether this is a causal, class-wide effect, one easy solution would be to avoid administering Plavix and a PPI too closely together. Although both Plavix and PPIs have a sustained pharamcological and tissue effect, their serum half-lives are very short (less than a few hours). Thus any drug interaction that results in a deleterious clinical effect (if one actually occurs) would be obviated if one drug was taken in the AM and the other in the PM.
If the effect of the PPIs are indeed via the P450 system, then the chances are that the difference in timing will not make a difference to the interaction.
There are a multiplicity of factors to be considered but most important are the relative association constants for the binding of the two ‘substrates’ and the relative off rates for their dissociation. This may be why pantoprazole has no effect, while omeprazole and others do.
how about combination aspirin and PPI